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A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, Odalasvir, and Simeprevir

Primary Purpose

Chronic Hepatitis C

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

AL-335

Odalasvir (ODV)

Simeprevir (SMV)

About this trial

This is an interventional treatment trial for Chronic Hepatitis C

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participant has provided written consent
In the Investigator's opinion, the participant is able to understand and comply with protocol requirements, instructions, and protocol stated restrictions and is likely to complete the study as planned
Male or female, 18-70 years of age
Body mass index (BMI) 18-35 kilogram per meter square (kg/m^2), inclusive
A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin) pregnancy test at screening
Female participants must either:
- not be of childbearing potential defined as: i. Postmenopausal for at least 12 months (that is [i.e.], 2 years of amenorrhea without an alternative medical cause) and a serum follicle stimulating hormone (FSH) level in the postmenopausal range (per reference laboratory), OR ii. Surgically sterile (example [e.g.], underwent total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation/bilateral tubal clips without reversal operation), or otherwise incapable of becoming pregnant, OR
- be of childbearing potential AND
- not heterosexually active (e.g., abstinent or homosexual) from screening until 6 months after study drug administration (or longer, if dictated by local regulations), OR
- if heterosexually active
  - have a vasectomized partner (confirmed sterile per verbal account of the participant), OR
  - using an acceptable method of birth control from screening and agree to continue to use the same method of contraception throughout the study and for 6 months after study drug administration (or longer, if dictated by local regulations). Oral hormone based contraceptives are not allowed from 14 days before the planned study drug administration until 6 months after the last dose of treatment due to the potential for drug-drug interactions which might undermine their efficacy. An intrauterine device (IUD), being either hormonal (i.e., Intra-Uterine System [IUS*]) or non-hormonal, is considered highly effective and reliable; therefore participants using an IUD/IUS are not required to use additional contraceptive methods (no double-barrier method is required). Other non-oral hormone-based contraception methods (e.g., injectable, implants, transdermal system, vaginal ring) may be continued, but as the interaction of the study drug with hormone-based contraception is unknown, these methods are not considered to be reliable and therefore participants should use a double-barrier method (e.g., male condom+either diaphragm or cervical cap with or without spermicide).
    - An IUS does not rely on systemic plasma concentrations and is therefore not expected to be impacted by a potential drug-drug interaction (DDI)
Note 1: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
Note 2: A male and female condom should not be used together due to risk of breakage or damage caused by latex friction
A post-menopausal female who is receiving hormone replacement therapy and is willing to discontinue hormone therapy 30 days before study drug dosing and agrees to remain off hormone replacement therapy for the duration of the study may be eligible for study participation.
- Male participants must either:
- be surgically sterile (had a vasectomy), or otherwise incapable of fathering a child, OR
- not be heterosexually active (e.g., abstinent or homosexual) from enrollment (Day 1) in the study until at least 6 months after study drug administration, OR
- if heterosexually active:
  - have a partner who is postmenopausal (2 years amenorrhea), surgically sterile (e.g., has had a total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation/bilateral tubal clips without reversal operation), or otherwise incapable of becoming pregnant OR
  - be practicing an acceptable method of birth control from enrollment in the study (Day 1) and agree to continue to use the same method of contraception throughout the study and for at least 6 months after study drug administration (or longer, if dictated by local regulations). An acceptable method of birth control for male participants is a double-barrier method (e.g., male condom+either diaphragm or cervical cap with or without spermicide).
Note: Male participants with a female partner who uses hormonal contraceptives (oral, injectable, implants) or a hormonal (IUS) or non-hormonal IUD and male participants who are vasectomized or otherwise incapable of fathering a child are not required to use additional contraceptive methods.
Note 1: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
Note 2: A male and female condom should not be used together due to risk of breakage or damage caused by latex friction.
NOTE: Contraceptive use by men and women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies if these are stricter than what is proposed in these inclusion criteria
Participants must agree to refrain from sperm/egg donation from start of dosing through 6 months after the completion of study drug administration
Genotype (GT) 1a or 1b or GT2 or 3 chronic hepatitis C (CHC), depending on cohort, with positive Hepatitis C virus (HCV) antibody and a positive HCV ribonucleic acid (RNA) at screening including documentation of CHC infection for at least 6 months. Genotype testing must occur at a screening visit. NOTE: GT1 patients are eligible for inclusion even if they cannot be successfully subtyped unless a specific subtype is required for a cohort
Screening HCV RNA viral load greater than or equal to (>=) 50,000 International Units per milliliter (IU/mL), except for participants with compensated cirrhosis (Child Pugh Class A) who may have HCV RNA viral load >=10^4 IU/mL
No prior treatment for CHC (defined as no prior exposure to any approved or investigational drug including direct-acting antivirals, and interferon-based treatments)
Fibroscan, collected within 6 months of baseline visit, with liver stiffness score less than or equal to (<=) 12.5 kilo Pascal (kPa) to be eligible (except for participants with cirrhosis, see below).
- participants with compensated cirrhosis must meet the Child-Pugh Class A definition (see Appendix G) and at least one of the following criteria: i. Liver biopsy result indicating the presence of cirrhosis (e.g., Metavir F4; Ishak >5) or ii. Fibroscan evaluation with a liver stiffness score >12.5 kPa
Participant is otherwise in good health as deemed by the investigator, based on the findings of a medical evaluation including medical history, physical examination, laboratory tests and electrocardiogram (ECG)
Willing to avoid prolonged sun exposure and use of tanning devices while taking Simeprevir (SMV) and through 4 weeks of follow up. Participant should also be advised to use a broad-spectrum sunscreen and lip balm of at least sun protection factor >30 to help protect against potential sunburn

Exclusion Criteria:

Pregnant, planning on becoming pregnant (during treatment and up to 6 months after the end of treatment [EOT]), or breast-feeding female participant, or male participant whose female partner is pregnant or planning on becoming pregnant (during treatment and up to 6 months after the EOT)
Other than CHC with or without compensated cirrhosis, clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid or any other medical illness or psychiatric disorder, as determined by the Investigator and/or Sponsor's Medical Monitor
History or other clinical evidence of significant or unstable cardiac disease (e.g., angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant ECG abnormalities), moderate to severe valvular disease or uncontrolled hypertension at screening
Screening echocardiogram ejection fraction <55 percentage (%) or any other echocardiographic finding suggestive of clinically relevant cardiomyopathy
Creatinine clearance of <60 mL/min (Cockcroft-Gault)
Positive test for Hepatitis A virus immunoglobulin (HAV) Immunoglobulin M (IgM), Hepatitis B surface antigen (HBsAg), or Human Immunodeficiency Virus (HIV) Ab
Abnormal screening laboratory results that are considered clinically significant by the investigator
History of clinical hepatic decompensation, e.g., variceal bleeding, spontaneous bacterial peritonitis, ascites, hepatic encephalopathy or active jaundice (within last year)
Any condition that, in the opinion of the investigator, would compromise the study's objectives or the well-being of the participant or prevent the participant from meeting the study requirements
Participation in an investigational drug trial or having received an investigational vaccine within 30 days or 5 half lives (whichever is longer) prior to study medication
Clinically significant abnormal screening ECG findings (e.g., PR >200 msec, QRS interval >120 millisecond (msec) or corrected QT interval (QTc) >450 msec for male participants and >470 msec for female participants), based on an average of triplicate ECGs. Any evidence of heart block or bundle branch block is also exclusionary
History or family history of abnormal ECG intervals, for example prolonged QT syndrome (torsade de pointes) or sudden cardiac death
The participant has a positive prestudy drug screen, including methadone unless the drug is prescribed by the participant's physician. The list of drugs that should be screened for includes amphetamines, barbiturates, cocaine, opiates, phencyclidine (PCP), and benzodiazepines
Laboratory abnormalities including:
- Hematocrit <0.34
- White blood cell counts <3,500/millimeter (mm)^3 (<1,000/mm^3 for participants with compensated cirrhosis)
- Absolute neutrophil count <1,000/mm^3 (<750/mm^3 for participants with compensated cirrhosis)
- Platelets <=120,000/mm^3 (platelets ≤90,000/mm^3 for participants with compensated cirrhosis)
- Glycosylated hemoglobin (HbA1C) >55 mmol/mol
- Prothrombin time >=1.5 * upper limit of normal (ULN)
- Albumin <=32 gram per liter (g/L), bilirubin >=1.5 milligram per deciliter (mg/dL) at screening (participants with documented Gilbert's disease allowed)
- Serum ALT concentration >=5* ULN
- CK >1.5* ULN A single repeat laboratory evaluation under appropriate conditions (e.g., fasted, no antecedent exercise) is allowed for eligibility determination
Any condition possibly affecting drug absorption (e.g., gastrectomy or other significant gastrointestinal tract surgery, such as gastroenterostomy, small bowel resection, or active enterostomy)
Clinically significant blood loss or elective blood donation of significant volume (i.e., >500 mL) within 60 days of first dose of study drug; >1 unit of plasma within 7 days of first dose of study drug
Evidence of clinically relevant active infection that would interfere with study conduct or its interpretation
History of regular alcohol intake >10 standard drinks per week of alcohol for females and >15 standard drinks per week for males (one unit is defined as 10 g alcohol) within 3 months of the screening visit
The use of prohibited medications, including prescription, over the counter (OTC) medications, herbal medications, inducers or inhibitors of Cytochrome P450 (CYP450) enzymes or drug transporters (including P-gp) within 14 days prior to the first dose of study medication is excluded, unless previously approved by the Sponsor's Medical Monitor. NOTE: Chronic medication use is permitted so long as they are medically necessary, deemed acceptable by the Principal Investigator and Medical Monitor, and not Prohibited Medications (see Section 5.12)
Hypersensitivity to the active substances (including sulfa allergy) or to any of the excipients of AL-335, Odalasvir (ODV) or SMV
Evidence on recent (within 6 months) liver ultrasound of hepatic mass or lesion concerning for malignancy (participants with cirrhosis only)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

Cohorts 1 and 2 (Without Cirrhosis) : AL-335+ODV+SMV

Cohort 1b (Without Cirrhosis) : AL-335+ODV

Cohort 3 (Without Cirrhosis) : AL-335+ODV+SMV

Cohort 4 (Without Cirrhosis) : AL-335+ODV

Cohort 5 (Without Cirrhosis) : AL-335+ODV + SMV

Cohorts 6, 7, 8 and 12 (With Cirrhosis) : AL-335+ODV+SMV

Cohorts 9, 10 and 11 (With Cirrhosis) : AL-335+ODV+SMV

Cohorts 12 to 15: AL-335+ODV With/without SMV

Arm Description

Treatment-naïve non-cirrhotic Hepatitis C virus (HCV)-infected participants will receive AL-335 and Odalasvir (ODV) with Simeprevir (SMV) for 8 weeks.

Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV for 8 weeks.

Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV for 6 weeks.

Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV up to 8 or 12 weeks.

Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV up to 8 or 12 weeks.

Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 8 weeks.

Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 12 weeks.

Based on safety, pharmacokinetic (PK), and viral load data, the treatment duration (4 to 12 weeks) and dose levels (AL-335: 400-1,200 milligram [mg], ODV: 25-50 mg with/without SMV: 75-150 mg) may be changed for ongoing and future cohorts (up to 15) after obtaining agreement from the Sponsor and the Principal Investigator.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Event (TEAE)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and up to 43 weeks that were absent before treatment or that worsened relative to pre-treatment state.

Body Weight at End of Treatment

Body weight (measured using a calibrated scale) at end of treatment was reported.

Body Mass Index (BMI) at End of Treatment

BMI was calculated by dividing the body weight (in kilogram) by the square of height (in meters). BMI at end of treatment was reported.

Percentage of Participants With Worst Post-Baseline Values of Vital Signs

Percentage of participants with worst post-baseline values of vital signs (Systolic blood pressure [sBP], Diastolic blood pressure [dBP], and Heart rate) were reported. For sBP, abnormally low: less than or equal to [<=] 90 millimeters mercury [mmHg]; Grade 1 or mild: greater than [>] 140 to less than [<] 160 mmHg; Grade 2 or moderate: >=160 to <180 and Grade 3 or severe: >=180 mmHg. For dBP, abnormally low: <=50 mmHg; Grade 1 or mild: >90 to <100 mmHg; Grade 2 or moderate: >=100 to <110 mmHg and Grade 3 or severe: >=110 mmHg. For Heart Rate, abnormally low: <=50 beats per minute [bpm] and abnormally high: >=120 bpm.

Percentage of Participants With Maximum Decrease From Baseline in Mean Ejection Fraction

Percentage of participants with maximum decrease from baseline in mean ejection fraction was reported. Percentages are based on the number of participants with available data.

Percentage of Participants by Treatment Emergent Toxicity Grade - Hematology Parameters

Percentage of participants by treatment emergent toxicity grade (1, 2, 3, 4 and 3+4) for Hematology parameters (hemoglobin, lymphocytes, neutrophils, leukocytes, platelets) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

Percentage of Participants by Treatment Emergent Toxicity Grade - Blood Chemistry Parameters

Percentage of participants by treatment emergent toxicity grade (Grade 1,2,3,4,3+4) for Blood Chemistry (Calcium, Phosphate, Potassium, Sodium, Bicarbonate, Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Direct bilirubin, Glucose, Cholesterol, Triglycerides, Urate, Triacylglycerol lipase, Creatinine, Creatinine clearance, Albumin and Creatine kinase) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

Percentage of Participants by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)

Percentage of participants by treatment emergent toxicity grade for coagulation parameter (Prothrombin International Normalized Ratio) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

Percentage of Participants by Treatment Emergent Toxicity Grade - Urinalysis Parameter (Protein)

Percentage of participants by treatment emergent toxicity grade (Grade 1, 2, 3, 4, 3+4) for urinalysis parameter (protein) was reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.

Percentage of Participants With Worst Treatment Emergent Abnormalities of Electrocardiogram (ECG) Parameters

Percentage of participants with worst treatment emergent abnormalities of ECG parameters (Fridericia Corrected QT interval [QTcF], Bazett Corrected QT interval [QTcB], Heart rate, QRS and PR, was reported. For QTcF abnormality was defined as 30 milliseconds (ms) less than or equal to (<=) QTcF increase from baseline <= 60 ms; for QTcB abnormality was defined as 30 ms <= QTcB increase from baseline <= 60 ms; for heart rate - abnormal low: <= 50 beats per minute (bpm) and abnormal high: >= 120 bpm; for QRS - abnormal high: >120 ms; for PR - abnormally low: PR < 120 ms; abnormally high - 200 ms < PR <= 240 ms and 240 ms < PR <= 300 ms.

Secondary Outcome Measures

Percentage of Participants With Sustained Virologic Response (SVR) at Week 4, 12 and 24 After End of Treatment

Participants were considered to have achieved SVR if the Hepatitis C virus (HCV) Ribonucleic acid (RNA) less than (<) Lower limit of quantification (LLOQ) (<15 international unit per milliliter [IU/mL]) detectable or undetectable at Week 4, 12 and 24 after the actual end of study drug treatment.

Minimum Observed Plasma Concentration (Cmin) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Cmin is the minimum observed plasma concentration of AL-335 and its metabolites (ALS-022399 and ALS-022227). For Pharmacokinetic (PK) analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Maximum Observed Plasma Concentration (Cmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Cmax is the maximum observed plasma concentration of AL-335 and its metabolites (ALS-022227). For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Trough Plasma Concentration (Ctrough) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Ctrough is the trough plasma concentration for AL-335 and its metabolites (ALS-022399 and ALS-022227). For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Tmax is the time to reach the maximum plasma concentration of AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

AUC(0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Area Under the Plasma Concentration Time-Curve at 24 Hours (AUC0-24) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

AUC(0-24) is the area under the plasma concentration-time curve from time zero to time 24 hours for AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Last Measurable Plasma Concentration (Clast) of AL-335 and Its Metabolite (ALS-022399 and ALS-022227)

Clast is the last measurable plasma concentration (Clast) of AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Tlast is the time corresponding to last measurable plasma concentration for AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Average Plasma Concentration at Steady State (Css,Avg) of ALS-022227

Css,avg is the average plasma concentration at steady state of ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Cmin of Simeprevir

Cmin is the minimum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Cmax of Simeprevir

Cmax is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Ctrough of Simeprevir

Ctrough is the trough plasma concentration of Simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Tmax of Simeprevir

Tmax is the Time to reach the maximum plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

AUC (0-last) of Simeprevir

AUC (0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

AUC (0-24) of Simeprevir

AUC (0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Clast of Simeprevir

Clast is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Tlast of Simeprevir

Tlast is the time corresponding to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Average Plasma Concentration at Steady State (Css,Avg) of Simeprevir

Css,avg is the average plasma concentration at steady state of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Cmin of Odalasvir

Cmin is the minimum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Cmax of Odalasvir

Cmax is the maximum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Ctrough of Odalasvir

Ctrough is the trough plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Tmax of Odalasvir

Tmax is the time to reach the maximum plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

AUC (0-last) of Odalasvir

AUC(0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

AUC (0-24) for Odalasvir

AUC(0-24) is the area under the plasma concentration-time curve from time zero to time 24 hours for odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Clast of Odalasvir

Clast is the last measurable plasma concentration (Clast) of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Tlast of Odalasvir

Tlast is the time corresponding to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Average Plasma Concentration at Steady State (Css,Avg) of Odalasvir

Css,avg is the average plasma concentration at steady state of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11).

Percentage of Participants With Virologic Relapse During the Follow-up Period

Viral relapse is defined as participants SVR12, with HCV RNA <LLOQ at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow up.

Percentage of Participants With On-treatment Failure

On-treatment failure was defined by participants who did not achieve SVR12 and with confirmed HCV RNA >= LLOQ at the actual end of study drug treatment.

Percentage of Participants Who Achieved HCV RNA Less Then (<) LLOQ Undetectable

Percentage of participants who achieved HCV RNA less then (<) LLOQ undetectable was reported.

Percentage of Participants Who Achieved HCV RNA <LLOQ

Percentage of participants who achieved HCV RNA <LLOQ was reported.

Time to Achieve Undetectable HCV RNA or < LLOQ HCV RNA

Time to achieve undetectable HCV RNA or < LLOQ HCV RNA was reported.

Number of Participants With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Participants With Virologic Failure

Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants with virologic failure.

Full Information

NCT ID

NCT02569710

First Posted

October 1, 2015

Last Updated

June 24, 2019

Sponsor

Alios Biopharma Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02569710

Brief Title

A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, Odalasvir, and Simeprevir

Official Title

A Phase 2a, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335 and Odalasvir, With or Without Simeprevir, in Treatment-Naïve Subjects With Genotype 1, 2 or 3 Chronic Hepatitis C Infection With or Without Compensated Child Pugh A Cirrhosis

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

October 31, 2015 (Actual)

Primary Completion Date

May 11, 2018 (Actual)

Study Completion Date

May 11, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alios Biopharma Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of AL-335 in combination with odalasvir (ODV) with or without simeprevir (SMV) in participants with genotype (GT)1 or GT2 or GT3 chronic hepatitis C (CHC) infection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

161 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohorts 1 and 2 (Without Cirrhosis) : AL-335+ODV+SMV

Arm Type

Experimental

Arm Description

Treatment-naïve non-cirrhotic Hepatitis C virus (HCV)-infected participants will receive AL-335 and Odalasvir (ODV) with Simeprevir (SMV) for 8 weeks.

Arm Title

Cohort 1b (Without Cirrhosis) : AL-335+ODV

Arm Type

Experimental

Arm Description

Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV for 8 weeks.

Arm Title

Cohort 3 (Without Cirrhosis) : AL-335+ODV+SMV

Arm Type

Experimental

Arm Description

Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV for 6 weeks.

Arm Title

Cohort 4 (Without Cirrhosis) : AL-335+ODV

Arm Type

Experimental

Arm Description

Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV up to 8 or 12 weeks.

Arm Title

Cohort 5 (Without Cirrhosis) : AL-335+ODV + SMV

Arm Type

Experimental

Arm Description

Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV up to 8 or 12 weeks.

Arm Title

Cohorts 6, 7, 8 and 12 (With Cirrhosis) : AL-335+ODV+SMV

Arm Type

Experimental

Arm Description

Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 8 weeks.

Arm Title

Cohorts 9, 10 and 11 (With Cirrhosis) : AL-335+ODV+SMV

Arm Type

Experimental

Arm Description

Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 12 weeks.

Arm Title

Cohorts 12 to 15: AL-335+ODV With/without SMV

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

AL-335

Intervention Description

AL-335 tablets will be administered in a dose range of 400 to 1200 mg once daily (QD).

Intervention Type

Drug

Intervention Name(s)

Odalasvir (ODV)

Other Intervention Name(s)

ACH-3102

Intervention Description

ODV capsules will be administered in a dose range of 25 to 50 mg.

Intervention Type

Drug

Intervention Name(s)

Simeprevir (SMV)

Intervention Description

SMV tablets will be administered in a dose range of 75 to 150 mg QD or every other day (QOD).

Primary Outcome Measure Information:

Title

Number of Participants With Treatment Emergent Adverse Event (TEAE)

Description

Time Frame

Up to 43 weeks

Title

Body Weight at End of Treatment

Description

Body weight (measured using a calibrated scale) at end of treatment was reported.

Time Frame

End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

Title

Body Mass Index (BMI) at End of Treatment

Description

BMI was calculated by dividing the body weight (in kilogram) by the square of height (in meters). BMI at end of treatment was reported.

Time Frame

End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

Title

Percentage of Participants With Worst Post-Baseline Values of Vital Signs

Description

Time Frame

Up to 43 weeks

Title

Percentage of Participants With Maximum Decrease From Baseline in Mean Ejection Fraction

Description

Percentage of participants with maximum decrease from baseline in mean ejection fraction was reported. Percentages are based on the number of participants with available data.

Time Frame

Baseline up to End of treatment (up to 43 weeks)

Title

Percentage of Participants by Treatment Emergent Toxicity Grade - Hematology Parameters

Description

Time Frame

Up to 43 weeks

Title

Percentage of Participants by Treatment Emergent Toxicity Grade - Blood Chemistry Parameters

Description

Time Frame

Up to 43 weeks

Title

Percentage of Participants by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)

Description

Time Frame

Up to 43 weeks

Title

Percentage of Participants by Treatment Emergent Toxicity Grade - Urinalysis Parameter (Protein)

Description

Time Frame

Up to 43 weeks

Title

Percentage of Participants With Worst Treatment Emergent Abnormalities of Electrocardiogram (ECG) Parameters

Description

Time Frame

Up to 43 weeks

Secondary Outcome Measure Information:

Title

Percentage of Participants With Sustained Virologic Response (SVR) at Week 4, 12 and 24 After End of Treatment

Description

Time Frame

At Week 4, 12 and Week 24 after end of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

Title

Minimum Observed Plasma Concentration (Cmin) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Maximum Observed Plasma Concentration (Cmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Trough Plasma Concentration (Ctrough) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Area Under the Plasma Concentration Time-Curve at 24 Hours (AUC0-24) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

Title

Last Measurable Plasma Concentration (Clast) of AL-335 and Its Metabolite (ALS-022399 and ALS-022227)

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227)

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Average Plasma Concentration at Steady State (Css,Avg) of ALS-022227

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Cmin of Simeprevir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Cmax of Simeprevir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Ctrough of Simeprevir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Tmax of Simeprevir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

AUC (0-last) of Simeprevir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

AUC (0-24) of Simeprevir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

Title

Clast of Simeprevir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Tlast of Simeprevir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Average Plasma Concentration at Steady State (Css,Avg) of Simeprevir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Cmin of Odalasvir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Cmax of Odalasvir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Ctrough of Odalasvir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Tmax of Odalasvir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

AUC (0-last) of Odalasvir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

AUC (0-24) for Odalasvir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

Title

Clast of Odalasvir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Tlast of Odalasvir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Average Plasma Concentration at Steady State (Css,Avg) of Odalasvir

Description

Time Frame

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

Title

Percentage of Participants With Virologic Relapse During the Follow-up Period

Description

Viral relapse is defined as participants SVR12, with HCV RNA <LLOQ at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow up.

Time Frame

Follow up period (Up to Week 12 after end of treatment)

Title

Percentage of Participants With On-treatment Failure

Description

On-treatment failure was defined by participants who did not achieve SVR12 and with confirmed HCV RNA >= LLOQ at the actual end of study drug treatment.

Time Frame

Up to 12 weeks

Title

Percentage of Participants Who Achieved HCV RNA Less Then (<) LLOQ Undetectable

Description

Percentage of participants who achieved HCV RNA less then (<) LLOQ undetectable was reported.

Time Frame

Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

Title

Percentage of Participants Who Achieved HCV RNA <LLOQ

Description

Percentage of participants who achieved HCV RNA <LLOQ was reported.

Time Frame

Title

Time to Achieve Undetectable HCV RNA or < LLOQ HCV RNA

Description

Time to achieve undetectable HCV RNA or < LLOQ HCV RNA was reported.

Time Frame

Up to Week 24 (follow up visit)

Title

Number of Participants With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Participants With Virologic Failure

Description

Time Frame

Up to Week 24 (Follow up visit)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant has provided written consent In the Investigator's opinion, the participant is able to understand and comply with protocol requirements, instructions, and protocol stated restrictions and is likely to complete the study as planned Male or female, 18-70 years of age Body mass index (BMI) 18-35 kilogram per meter square (kg/m^2), inclusive A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin) pregnancy test at screening Female participants must either: not be of childbearing potential defined as: i. Postmenopausal for at least 12 months (that is [i.e.], 2 years of amenorrhea without an alternative medical cause) and a serum follicle stimulating hormone (FSH) level in the postmenopausal range (per reference laboratory), OR ii. Surgically sterile (example [e.g.], underwent total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation/bilateral tubal clips without reversal operation), or otherwise incapable of becoming pregnant, OR be of childbearing potential AND not heterosexually active (e.g., abstinent or homosexual) from screening until 6 months after study drug administration (or longer, if dictated by local regulations), OR if heterosexually active have a vasectomized partner (confirmed sterile per verbal account of the participant), OR using an acceptable method of birth control from screening and agree to continue to use the same method of contraception throughout the study and for 6 months after study drug administration (or longer, if dictated by local regulations). Oral hormone based contraceptives are not allowed from 14 days before the planned study drug administration until 6 months after the last dose of treatment due to the potential for drug-drug interactions which might undermine their efficacy. An intrauterine device (IUD), being either hormonal (i.e., Intra-Uterine System [IUS*]) or non-hormonal, is considered highly effective and reliable; therefore participants using an IUD/IUS are not required to use additional contraceptive methods (no double-barrier method is required). Other non-oral hormone-based contraception methods (e.g., injectable, implants, transdermal system, vaginal ring) may be continued, but as the interaction of the study drug with hormone-based contraception is unknown, these methods are not considered to be reliable and therefore participants should use a double-barrier method (e.g., male condom+either diaphragm or cervical cap with or without spermicide). An IUS does not rely on systemic plasma concentrations and is therefore not expected to be impacted by a potential drug-drug interaction (DDI) Note 1: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. Note 2: A male and female condom should not be used together due to risk of breakage or damage caused by latex friction A post-menopausal female who is receiving hormone replacement therapy and is willing to discontinue hormone therapy 30 days before study drug dosing and agrees to remain off hormone replacement therapy for the duration of the study may be eligible for study participation. Male participants must either: be surgically sterile (had a vasectomy), or otherwise incapable of fathering a child, OR not be heterosexually active (e.g., abstinent or homosexual) from enrollment (Day 1) in the study until at least 6 months after study drug administration, OR if heterosexually active: have a partner who is postmenopausal (2 years amenorrhea), surgically sterile (e.g., has had a total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation/bilateral tubal clips without reversal operation), or otherwise incapable of becoming pregnant OR be practicing an acceptable method of birth control from enrollment in the study (Day 1) and agree to continue to use the same method of contraception throughout the study and for at least 6 months after study drug administration (or longer, if dictated by local regulations). An acceptable method of birth control for male participants is a double-barrier method (e.g., male condom+either diaphragm or cervical cap with or without spermicide). Note: Male participants with a female partner who uses hormonal contraceptives (oral, injectable, implants) or a hormonal (IUS) or non-hormonal IUD and male participants who are vasectomized or otherwise incapable of fathering a child are not required to use additional contraceptive methods. Note 1: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. Note 2: A male and female condom should not be used together due to risk of breakage or damage caused by latex friction. NOTE: Contraceptive use by men and women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies if these are stricter than what is proposed in these inclusion criteria Participants must agree to refrain from sperm/egg donation from start of dosing through 6 months after the completion of study drug administration Genotype (GT) 1a or 1b or GT2 or 3 chronic hepatitis C (CHC), depending on cohort, with positive Hepatitis C virus (HCV) antibody and a positive HCV ribonucleic acid (RNA) at screening including documentation of CHC infection for at least 6 months. Genotype testing must occur at a screening visit. NOTE: GT1 patients are eligible for inclusion even if they cannot be successfully subtyped unless a specific subtype is required for a cohort Screening HCV RNA viral load greater than or equal to (>=) 50,000 International Units per milliliter (IU/mL), except for participants with compensated cirrhosis (Child Pugh Class A) who may have HCV RNA viral load >=10^4 IU/mL No prior treatment for CHC (defined as no prior exposure to any approved or investigational drug including direct-acting antivirals, and interferon-based treatments) Fibroscan, collected within 6 months of baseline visit, with liver stiffness score less than or equal to (<=) 12.5 kilo Pascal (kPa) to be eligible (except for participants with cirrhosis, see below). participants with compensated cirrhosis must meet the Child-Pugh Class A definition (see Appendix G) and at least one of the following criteria: i. Liver biopsy result indicating the presence of cirrhosis (e.g., Metavir F4; Ishak >5) or ii. Fibroscan evaluation with a liver stiffness score >12.5 kPa Participant is otherwise in good health as deemed by the investigator, based on the findings of a medical evaluation including medical history, physical examination, laboratory tests and electrocardiogram (ECG) Willing to avoid prolonged sun exposure and use of tanning devices while taking Simeprevir (SMV) and through 4 weeks of follow up. Participant should also be advised to use a broad-spectrum sunscreen and lip balm of at least sun protection factor >30 to help protect against potential sunburn Exclusion Criteria: Pregnant, planning on becoming pregnant (during treatment and up to 6 months after the end of treatment [EOT]), or breast-feeding female participant, or male participant whose female partner is pregnant or planning on becoming pregnant (during treatment and up to 6 months after the EOT) Other than CHC with or without compensated cirrhosis, clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid or any other medical illness or psychiatric disorder, as determined by the Investigator and/or Sponsor's Medical Monitor History or other clinical evidence of significant or unstable cardiac disease (e.g., angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant ECG abnormalities), moderate to severe valvular disease or uncontrolled hypertension at screening Screening echocardiogram ejection fraction <55 percentage (%) or any other echocardiographic finding suggestive of clinically relevant cardiomyopathy Creatinine clearance of <60 mL/min (Cockcroft-Gault) Positive test for Hepatitis A virus immunoglobulin (HAV) Immunoglobulin M (IgM), Hepatitis B surface antigen (HBsAg), or Human Immunodeficiency Virus (HIV) Ab Abnormal screening laboratory results that are considered clinically significant by the investigator History of clinical hepatic decompensation, e.g., variceal bleeding, spontaneous bacterial peritonitis, ascites, hepatic encephalopathy or active jaundice (within last year) Any condition that, in the opinion of the investigator, would compromise the study's objectives or the well-being of the participant or prevent the participant from meeting the study requirements Participation in an investigational drug trial or having received an investigational vaccine within 30 days or 5 half lives (whichever is longer) prior to study medication Clinically significant abnormal screening ECG findings (e.g., PR >200 msec, QRS interval >120 millisecond (msec) or corrected QT interval (QTc) >450 msec for male participants and >470 msec for female participants), based on an average of triplicate ECGs. Any evidence of heart block or bundle branch block is also exclusionary History or family history of abnormal ECG intervals, for example prolonged QT syndrome (torsade de pointes) or sudden cardiac death The participant has a positive prestudy drug screen, including methadone unless the drug is prescribed by the participant's physician. The list of drugs that should be screened for includes amphetamines, barbiturates, cocaine, opiates, phencyclidine (PCP), and benzodiazepines Laboratory abnormalities including: Hematocrit <0.34 White blood cell counts <3,500/millimeter (mm)^3 (<1,000/mm^3 for participants with compensated cirrhosis) Absolute neutrophil count <1,000/mm^3 (<750/mm^3 for participants with compensated cirrhosis) Platelets <=120,000/mm^3 (platelets ≤90,000/mm^3 for participants with compensated cirrhosis) Glycosylated hemoglobin (HbA1C) >55 mmol/mol Prothrombin time >=1.5 * upper limit of normal (ULN) Albumin <=32 gram per liter (g/L), bilirubin >=1.5 milligram per deciliter (mg/dL) at screening (participants with documented Gilbert's disease allowed) Serum ALT concentration >=5* ULN CK >1.5* ULN A single repeat laboratory evaluation under appropriate conditions (e.g., fasted, no antecedent exercise) is allowed for eligibility determination Any condition possibly affecting drug absorption (e.g., gastrectomy or other significant gastrointestinal tract surgery, such as gastroenterostomy, small bowel resection, or active enterostomy) Clinically significant blood loss or elective blood donation of significant volume (i.e., >500 mL) within 60 days of first dose of study drug; >1 unit of plasma within 7 days of first dose of study drug Evidence of clinically relevant active infection that would interfere with study conduct or its interpretation History of regular alcohol intake >10 standard drinks per week of alcohol for females and >15 standard drinks per week for males (one unit is defined as 10 g alcohol) within 3 months of the screening visit The use of prohibited medications, including prescription, over the counter (OTC) medications, herbal medications, inducers or inhibitors of Cytochrome P450 (CYP450) enzymes or drug transporters (including P-gp) within 14 days prior to the first dose of study medication is excluded, unless previously approved by the Sponsor's Medical Monitor. NOTE: Chronic medication use is permitted so long as they are medically necessary, deemed acceptable by the Principal Investigator and Medical Monitor, and not Prohibited Medications (see Section 5.12) Hypersensitivity to the active substances (including sulfa allergy) or to any of the excipients of AL-335, Odalasvir (ODV) or SMV Evidence on recent (within 6 months) liver ultrasound of hepatic mass or lesion concerning for malignancy (participants with cirrhosis only)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alios Biopharma Inc. Clinical Trial

Organizational Affiliation

Alios Biopharma Inc.

Official's Role

Study Director

Facility Information:

Facility Name

CAP Research Ltd

City

Phoenix

Country

Mauritius

Facility Name

Republican Clinical Hospital

City

Chisinau

Country

Moldova, Republic of

Facility Name

Auckland Clinical Studies

City

Auckland

ZIP/Postal Code

1150

Country

New Zealand

Facility Name

Christchurch Clinical Studies Trust

City

Christchurch

ZIP/Postal Code

8011

Country

New Zealand

Facility Name

Waikato Hospital

City

Hamilton

Country

New Zealand

Facility Name

P3 Research Ltd - Hawkes Bay

City

Havelock North

Country

New Zealand

Facility Name

P3 Research Ltd - Wellington

City

Wellington

Country

New Zealand

Facility Name

Wellington Hospital

City

Wellington

Country

New Zealand

Facility Name

King's College Hospital

City

Brixton

Country

United Kingdom

Facility Name

NHS Greater Glasgow and Clyde Glasgow Royal Infirmary

City

Glasgow

Country

United Kingdom

Facility Name

Pennine Acute Hospitals Trust

City

Oldham

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, Odalasvir, and Simeprevir

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A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, Odalasvir, and Simeprevir

Chronic Hepatitis C

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial