Back to resultsStudy of Safety and Tolerability of DCR HBVS
Primary Purpose
Hepatitis B, Chronic
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DCR-HBVS
Placebo for DCR-HBVS
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B, Chronic focused on measuring Chronic Hepatitis B, DNA Virus Infections, CHB, HBsAg, Liver Disease, RNAi
Eligibility Criteria
Inclusion Criteria:
- Healthy at the time of screening as determined by medical evaluation.
- Capable of giving informed consent.
- 12-lead ECG within normal limits or with no clinically significant abnormalities.
- Negative screen for alcohol or drugs of abuse.
- Non-smokers for at least 3 months with a negative urinary cotinine concentration at screening.
- BMI within range 18.0 - 32.0 kg/m2 (inclusive).
- Female participants not pregnant, not breastfeeding, and not of childbearing potential or willing to follow contraceptive guidance.
- Chronic hepatitis B infection (Group B and C only).
- Clinical history compatible with compensated liver disease with no evidence of cirrhosis (Group B and C only).
- Continuously on nucleotides (NUC) therapy for at least 12 weeks prior to screening (Group C only).
Exclusion Criteria:
- History of any medical condition that may interfere with the absorption, distribution, or elimination of study drug.
- Poorly controlled or unstable hypertension.
- History of diabetes mellitus treated with insulin or hypoglycemic agents.
- History of asthma requiring hospital admission within the preceding 12 months.
- Evidence of G-6-PD deficiency.
- Currently poorly controlled endocrine conditions, excluding thyroid conditions.
- History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
- Clinically relevant surgical history.
- Use of prescription medications (excluding contraception for women) within 4 weeks prior to the administration of study intervention.
- Use of clinically relevant over-the-counter medication or supplements (excluding routine vitamins) within 7 days of first dosing.
- Has received an investigational agent within the 3 months prior to dosing or is in follow-up of another study.
- Antiviral therapy (other than entecavir or tenofovir) within 3 months of screening or treatment with interferon in the last 3 years (Group B and C only).
- Use within the last 6 months of anticoagulants or systemically administered corticosteroids, immunomodulators, or immunosuppressants (Group B and C only).
Sites / Locations
- Monash Health
- St Vincent's Hospital Melbourne
- Queen Mary Hospital (The University of Hong Kong)
- Seoul National University Hospital
- Seoul Metropolitan Government - Seoul National University Boramae Medical Center
- Clinical Site
- Middlemore Hospital
- King Culalongkorn Memorial Hospital
- Srinagarind Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Arm 16
Arm 17
Arm 18
Arm 19
Arm 20
Arm 21
Arm 22
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort A1 DCR-HBVS
Cohort A1 Placebo
Cohort A2 DCR-HBVS
Cohort A2 Placebo
Cohort A3 DCR-HBVS
Cohort A3 Placebo
Cohort A4 DCR-HBVS
Cohort A4 Placebo
Cohort A5 DCR-HBVS
Cohort A5 Placebo
Cohort B DCR-HBVS
Cohort B Placebo
Cohort C1 DCR-HBVS
Cohort C1 Placebo
Cohort C2 DCR-HBVS
Cohort C2 Placebo
Cohort C3 DCR-HBVS
Cohort C3 Placebo
Cohort 4C DCR-HBVS
Cohort 5C1 DCR-HBVS
Cohort 5C2 DCR-HBVS
Cohort 5C3 DCR-HBVS
Arm Description
Single dose, Subcutaneous injection of 0.1mg/kg of DCR-HBVS (HV)
Single dose, Subcutaneous injection of 0.1mg/kg of Placebo for DCR-HBVS (HV)
Single dose, Subcutaneous injection of 1.5mg/kg of DCR-HBVS (HV)
Single dose, Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS (HV)
Single dose, Subcutaneous injection of 3mg/kg of DCR-HBVS (HV)
Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (HV)
Single dose, Subcutaneous injection of 6mg/kg of DCR-HBVS (HV)
Single dose, Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS (HV)
Single dose, Subcutaneous injection of 12mg/kg of DCR-HBVS (HV)
Single dose, Subcutaneous injection of 12mg/kg of Placebo for DCR-HBVS (HV)
Single dose, Subcutaneous injection of 3mg/kg of for DCR-HBVS (NUC naïve, CHB)
Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (NUC naïve, CHB)
4 doses- Subcutaneous injection of 1.5mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
4 doses- Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
4 doses- Subcutaneous injection of 3mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
4 doses- Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
4 doses- Subcutaneous injection of 6mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
4 doses- Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
1 dose- Subcutaneous injection of 100mg (NUC experienced, CHB) 1 dose- Subcutaneous injection of 200mg (NUC experienced, CHB) 1 dose- Subcutaneous injection of 400mg (NUC experienced, CHB)
4 doses- Subcutaneous injection of 200mg administered every 4 weeks (NUC experienced, CHB)
2 doses- Subcutaneous injection of 200mg administered every 8 weeks (NUC experienced, CHB)
2 doses- Subcutaneous injection of 400mg administered every 12 weeks (NUC experienced, CHB)
Outcomes
Primary Outcome Measures
Number of healthy volunteers with Adverse Events as assessed by CTCAE v5.0
Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings
Number participants with non-cirrhotic chronic Hepatitis B with Adverse Events as assessed by CTCAE v5.0
Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings
Secondary Outcome Measures
To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring plasma pharmacokinetics profiles of DCR-S219
Measure the amount of DCR-HBVS excreted in urine
To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring through concentrations of DCR-S219
Measure the amount of DCR-HBVS renal clearance (CLR).
To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring plasma pharmacokinetics profiles of DCR-HBVS.
Measure the amount of DCR-HBVS excreted in urine
To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring through concentrations of DCR-HBVS.
Measure DCR-HBVS renal clearance (CLR).
Full Information
NCT ID
NCT03772249
First Posted
December 3, 2018
Last Updated
September 28, 2022
Sponsor
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
1. Study Identification
Unique Protocol Identification Number
NCT03772249
Brief Title
Study of Safety and Tolerability of DCR HBVS
Official Title
A Three-Part, Phase 1, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of DCR-HBVS in Healthy Volunteers and Patients With Chronic Hepatitis B
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
December 28, 2018 (Actual)
Primary Completion Date
July 12, 2022 (Actual)
Study Completion Date
July 12, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
DCR-HBVS will be evaluated for safety and efficacy in healthy volunteers and chronic hepatitis B patients.
Detailed Description
DCR HBVS is being developed for the treatment of chronic hepatitis B (CHB) in adults. The study will be conducted in 3 parts, a single ascending-dose (SAD) phase in normal healthy volunteers (Group A), a single-dose (SD) phase in patients with CHB (Group B), and a multiple ascending-dose (MAD) phase in patients with CHB (Group 1c-3c). Cohort 4c is a single ascending dose with a possible duration of up to 48 weeks. Cohort 5c is a multiple dose cohort with a possible duration of up to 72 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic
Keywords
Chronic Hepatitis B, DNA Virus Infections, CHB, HBsAg, Liver Disease, RNAi
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Progression from the SAD phase to the first cohort in the MAD phase is contingent upon the Safety Review Committee (SRC) review of a minimum of 14 days post-dose safety and tolerability data from all NHV in at least the first 2 SAD cohorts. The SRC will select one (or more) well-tolerated dose(s) from the SAD phase for administration in the SD and MAD phases. Group B at 3 mg/kg will start in parallel with Group C at the 3 mg/kg dose level. In all study phases, dosing will be staggered with the use of sentinel participants to allow time for the assessment of safety before additional subjects are exposed to study drug. The fixed dosing regimen for Cohorts 4c and 5c was determined following SRC review and assessment of all data up to Cohort 3c. No sentinel dosing will occur in Cohorts 4c and 5c.
Masking
ParticipantCare ProviderInvestigator
Masking Description
This is a double-blind study in which the study site team, the Sponsor, and the participants will be blinded to treatment assignment. The unblinded pharmacist will cover each syringe, prior to transport to the bedside, to ensure blinding. The drug will be injected by an unblinded nurse or physician who is not part of the study team. Participants will be centrally assigned to randomized study intervention using an Interactive Voice/Web Response System (IVRS/IWRS). Cohorts 4c and 5c will be open label.
Allocation
Randomized
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A1 DCR-HBVS
Arm Type
Experimental
Arm Description
Single dose, Subcutaneous injection of 0.1mg/kg of DCR-HBVS (HV)
Arm Title
Cohort A1 Placebo
Arm Type
Placebo Comparator
Arm Description
Single dose, Subcutaneous injection of 0.1mg/kg of Placebo for DCR-HBVS (HV)
Arm Title
Cohort A2 DCR-HBVS
Arm Type
Experimental
Arm Description
Single dose, Subcutaneous injection of 1.5mg/kg of DCR-HBVS (HV)
Arm Title
Cohort A2 Placebo
Arm Type
Placebo Comparator
Arm Description
Single dose, Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS (HV)
Arm Title
Cohort A3 DCR-HBVS
Arm Type
Experimental
Arm Description
Single dose, Subcutaneous injection of 3mg/kg of DCR-HBVS (HV)
Arm Title
Cohort A3 Placebo
Arm Type
Placebo Comparator
Arm Description
Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (HV)
Arm Title
Cohort A4 DCR-HBVS
Arm Type
Experimental
Arm Description
Single dose, Subcutaneous injection of 6mg/kg of DCR-HBVS (HV)
Arm Title
Cohort A4 Placebo
Arm Type
Placebo Comparator
Arm Description
Single dose, Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS (HV)
Arm Title
Cohort A5 DCR-HBVS
Arm Type
Experimental
Arm Description
Single dose, Subcutaneous injection of 12mg/kg of DCR-HBVS (HV)
Arm Title
Cohort A5 Placebo
Arm Type
Placebo Comparator
Arm Description
Single dose, Subcutaneous injection of 12mg/kg of Placebo for DCR-HBVS (HV)
Arm Title
Cohort B DCR-HBVS
Arm Type
Experimental
Arm Description
Single dose, Subcutaneous injection of 3mg/kg of for DCR-HBVS (NUC naïve, CHB)
Arm Title
Cohort B Placebo
Arm Type
Placebo Comparator
Arm Description
Single dose, Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS (NUC naïve, CHB)
Arm Title
Cohort C1 DCR-HBVS
Arm Type
Experimental
Arm Description
4 doses- Subcutaneous injection of 1.5mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
Arm Title
Cohort C1 Placebo
Arm Type
Placebo Comparator
Arm Description
4 doses- Subcutaneous injection of 1.5mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
Arm Title
Cohort C2 DCR-HBVS
Arm Type
Experimental
Arm Description
4 doses- Subcutaneous injection of 3mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
Arm Title
Cohort C2 Placebo
Arm Type
Placebo Comparator
Arm Description
4 doses- Subcutaneous injection of 3mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
Arm Title
Cohort C3 DCR-HBVS
Arm Type
Experimental
Arm Description
4 doses- Subcutaneous injection of 6mg/kg of DCR-HBVS administered every 28 days (NUC experienced, CHB)
Arm Title
Cohort C3 Placebo
Arm Type
Placebo Comparator
Arm Description
4 doses- Subcutaneous injection of 6mg/kg of Placebo for DCR-HBVS administered every 28 days (NUC experienced, CHB)
Arm Title
Cohort 4C DCR-HBVS
Arm Type
Experimental
Arm Description
1 dose- Subcutaneous injection of 100mg (NUC experienced, CHB)
1 dose- Subcutaneous injection of 200mg (NUC experienced, CHB)
1 dose- Subcutaneous injection of 400mg (NUC experienced, CHB)
Arm Title
Cohort 5C1 DCR-HBVS
Arm Type
Experimental
Arm Description
4 doses- Subcutaneous injection of 200mg administered every 4 weeks (NUC experienced, CHB)
Arm Title
Cohort 5C2 DCR-HBVS
Arm Type
Experimental
Arm Description
2 doses- Subcutaneous injection of 200mg administered every 8 weeks (NUC experienced, CHB)
Arm Title
Cohort 5C3 DCR-HBVS
Arm Type
Experimental
Arm Description
2 doses- Subcutaneous injection of 400mg administered every 12 weeks (NUC experienced, CHB)
Intervention Type
Drug
Intervention Name(s)
DCR-HBVS
Other Intervention Name(s)
DCR-S219
Intervention Description
DCR-HBVS is a synthetic ribonucleic acid interference (RNAi) drug that consists of a double-stranded oligonucleotide conjugated to N-acetyl-D-galactosamine (GalNAc) ligands. DCR-HBVS is a sterile solution of the siRNA (DCR-S219) at a concentration of 195 mg/mL in water for injection (WFI).
Intervention Type
Drug
Intervention Name(s)
Placebo for DCR-HBVS
Other Intervention Name(s)
Placebo
Intervention Description
Sterile 9% saline for injection.
Primary Outcome Measure Information:
Title
Number of healthy volunteers with Adverse Events as assessed by CTCAE v5.0
Description
Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings
Time Frame
4 weeks
Title
Number participants with non-cirrhotic chronic Hepatitis B with Adverse Events as assessed by CTCAE v5.0
Description
Number of participants with abnormalities in vital signs, electrocardiogram (ECG), and clinically significant laboratory findings
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring plasma pharmacokinetics profiles of DCR-S219
Description
Measure the amount of DCR-HBVS excreted in urine
Time Frame
4 weeks
Title
To characterize the pharmacokinetics of DCR-HBVS in healthy volunteers by monitoring through concentrations of DCR-S219
Description
Measure the amount of DCR-HBVS renal clearance (CLR).
Time Frame
4 weeks
Title
To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring plasma pharmacokinetics profiles of DCR-HBVS.
Description
Measure the amount of DCR-HBVS excreted in urine
Time Frame
12 weeks
Title
To characterize the pharmacokinetics of DCR-HBVS in participants with non-cirrhotic CHB by monitoring through concentrations of DCR-HBVS.
Description
Measure DCR-HBVS renal clearance (CLR).
Time Frame
12 weeks
Other Pre-specified Outcome Measures:
Title
To evaluate the preliminary antiviral efficacy of DCR-HBVS in participants with CHB by monitoring changes in serum HBsAg levels (all Group B and C participants)during and after single dose and 12 weeks of treatment with DCR HBVS.
Description
Proportion of participants achieving at least a 1-log reduction in HBsAg AND achieving a HBsAg level < 100 IU/mL at last scheduled visit Time to HBsAg loss (Kaplan-Mayer) Time to anti-HBs seroconversion
Time Frame
12 weeks
Title
To evaluate the preliminary antiviral efficacy of DCR-HBVS in participants with CHB by monitoring HBeAg levels (HBeAg+ participants only) during and after single dose and 12 weeks of treatment with DCR HBVS.
Description
% of participants with HBeAg loss and anti HBe at last scheduled visit (if HBeAg positive at study entry)
Time Frame
12 weeks
Title
To evaluate the preliminary antiviral efficacy of DCR-HBVS in participants with CHB by monitoring HBV DNA levels (all Group B and C participants) during and after single dose and 12 weeks of treatment with DCR HBVS.
Description
Proportion of participants achieving HBV DNA < 2000 IU/mL (if > 2,000 IU/mL at Baseline); and proportion of participants achieving PCR-nondetectable HBV DNA (if HBV DNA was detectable at Baseline).
Time Frame
12 weeks
Title
To characterize the pharmacodynamics (PD) of DCR-HBVS on plasma levels of HBsAg and HBV in blood.
Description
Track post-treatment duration of any observed efficacy effects.
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy at the time of screening as determined by medical evaluation.
Capable of giving informed consent.
12-lead ECG within normal limits or with no clinically significant abnormalities.
Negative screen for alcohol or drugs of abuse.
Non-smokers for at least 3 months with a negative urinary cotinine concentration at screening.
BMI within range 18.0 - 32.0 kg/m2 (inclusive).
Female participants not pregnant, not breastfeeding, and not of childbearing potential or willing to follow contraceptive guidance.
Chronic hepatitis B infection (Group B and C only).
Clinical history compatible with compensated liver disease with no evidence of cirrhosis (Group B and C only).
Continuously on nucleotides (NUC) therapy for at least 12 weeks prior to screening (Group C only).
Exclusion Criteria:
History of any medical condition that may interfere with the absorption, distribution, or elimination of study drug.
Poorly controlled or unstable hypertension.
History of diabetes mellitus treated with insulin or hypoglycemic agents.
History of asthma requiring hospital admission within the preceding 12 months.
Evidence of G-6-PD deficiency.
Currently poorly controlled endocrine conditions, excluding thyroid conditions.
History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
Clinically relevant surgical history.
Use of prescription medications (excluding contraception for women) within 4 weeks prior to the administration of study intervention.
Use of clinically relevant over-the-counter medication or supplements (excluding routine vitamins) within 7 days of first dosing.
Has received an investigational agent within the 3 months prior to dosing or is in follow-up of another study.
Antiviral therapy (other than entecavir or tenofovir) within 3 months of screening or treatment with interferon in the last 3 years (Group B and C only).
Use within the last 6 months of anticoagulants or systemically administered corticosteroids, immunomodulators, or immunosuppressants (Group B and C only).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Bowman, MD
Organizational Affiliation
Dicerna Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Monash Health
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
St Vincent's Hospital Melbourne
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Queen Mary Hospital (The University of Hong Kong)
City
Hong Kong
Country
Hong Kong
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul Metropolitan Government - Seoul National University Boramae Medical Center
City
Soeul
Country
Korea, Republic of
Facility Name
Clinical Site
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
Middlemore Hospital
City
Auckland
Country
New Zealand
Facility Name
King Culalongkorn Memorial Hospital
City
Bangkok
Country
Thailand
Facility Name
Srinagarind Hospital
City
Khon Kaen
Country
Thailand
12. IPD Sharing Statement
Learn more about this trial
Study of Safety and Tolerability of DCR HBVS
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