A Study in Healthy Japanese Participants to Evaluate the Safety and Pharmacokinetics of Otilimab
Primary Purpose
Arthritis, Rheumatoid
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Otilimab
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Japanese participants, Otilimab, Pharmacokinetics, Rheumatoid arthritis, Safety, Tolerability
Eligibility Criteria
Inclusion criteria:
- Participant must be 20 to 50 years of age inclusive, at the time of signing the informed consent.
- Japanese participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- A Coronavirus Disease-2019 (COVID-19) screening with negative test: Two consecutive approved molecular tests (Polymerase chain reaction [PCR] or antigen test) separated by greater than (>)24 hours. The second test should be within 72 hours of admission to the unit on Day -1.
- Body mass index (BMI) within the range 18.5 to 24.9 kilograms per meter square (kg/m^2) (inclusive).
Exclusion Criteria:
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- Active infections (including localized infections), or history of recurrent infections (excluding recurrent fungal infections of the nail bed), or has required management of acute or chronic infections
- History of any respiratory disease which (in the opinion of the investigator) would compromise participant safety or the ability of the participant to complete the study.
- Clinically-significant or unstable (in the opinion of the investigator) persistent cough or dyspnea that is unexplained.
- Current or previous active Tuberculosis (TB), history of untreated or incompletely treated active or latent TB, suspected or known extra pulmonary TB.
- Previous close contact with a person with active TB and did not receive satisfactory anti-tuberculosis treatment as per World Health Organization (WHO) or national guidelines.
- Hemoglobin less than or equal to (<=)9 grams per deciliter (g/dL); white blood cell (WBC) count <=3.0 times 10^9/ Liter (L); platelet count <=100 times 10^9/L; absolute neutrophil count (ANC) <=1.0 times 10^9/L; lymphocyte count <=0.75 times 10^9/L at screening.
- A vaccination (live or attenuated) within 30 days prior to Day 1 or Bacillus Calmette-Guerin (BCG) vaccination within 365 days prior to Day 1, or a live vaccination planned during the course of the study. Any COVID-19 vaccination within 14 days prior to enrolment.
- Any surgical procedure, including bone or joint surgery/synovectomy within 8 weeks prior to Day 1 or any planned surgery within the duration of the study.
- Significant allergies to humanized Monoclonal antibody (mAb).
- Participants with known COVID-19 positive contacts within 14 days prior to screening.
- History of lymphoma, leukemia, or any malignancy.
- History of infected joint prosthesis at any time, with the prosthesis still in situ. History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections.
- Use of prescription or non-prescription drugs within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study intervention until completion of the evaluation visit, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.
- Treatment with biologic agents (such as mAb including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
- Blood donation/sampling within 60 days prior to screening.
- The participant with positive Serological test for syphilis, Human immunodeficiency virus (HIV) antigen/antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody.
- The participant with positive test for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis B surface antibody (HBsAb), or Hepatitis C virus (HCV) antibody.
- Positive pre-study drug/alcohol screen.
- Participants with signs and symptoms suggestive of COVID-19 (fever, cough) within 14 days prior inpatient admission on Day -1.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Healthy Japanese participants receiving otilimab
Arm Description
Outcomes
Primary Outcome Measures
Maximum drug concentration (Cmax) following administration of otilimab
Area under the concentration-time curve from pre-dose to infinity (AUC[0-infinity]) following administration of otilimab
Secondary Outcome Measures
Area under the plasma concentration-time curve from pre-dose to t (AUC[0-t]) following administration of otilimab
Time to maximum plasma concentration (Tmax) following administration of otilimab
Elimination half-life (t1/2) following administration of otilimab
Time to reach the last quantifiable plasma concentration (Tlast) following administration of otilimab
Number of participants with Adverse events (AEs), Serious adverse events (SAEs) and Adverse events of special interests (AESIs)
Change from Baseline in hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count (Giga cells per liter)
Change from Baseline in hematology parameter: Red blood cell (RBC) count (Trillion cells per liter)
Change from Baseline in hematology parameter: Hemoglobin (Grams per Liter)
Change from Baseline in hematology parameter: Hematocrit (Proportion of red blood cells in blood)
Change from Baseline in hematology parameter: Mean Corpuscular Volume (MCV) (Femtoliters)
Change from Baseline in hematology parameter: Mean corpuscular hemoglobin (MCH) (Picograms)
Change from Baseline in hematology parameter: Percentage of reticulocytes (Percentage of reticulocytes)
Change from Baseline in clinical chemistry parameters: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Creatine kinase, Gamma Glutamyl transferase (GGT), Lactate Dehydrogenase (International units per Liter)
Change from Baseline in clinical chemistry parameters: Calcium, glucose, potassium, sodium, Chloride, Phosphate and Blood urea nitrogen (BUN) (Millimoles per Liter)
Change from Baseline in clinical chemistry parameters: Creatinine, direct bilirubin, total bilirubin and uric acid (Micromoles per liter)
Change from Baseline in clinical chemistry parameters: Albumin and Total protein (Grams per liter)
Change from Baseline in clinical chemistry parameter: C-reactive protein (CRP) (Milligrams per liter
Change from Baseline in clinical chemistry parameter: Amylase (Units per liter)
Change from Baseline in lipid panel parameters: Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides (Millimoles per Liter)
Number of participants with abnormal urinalysis parameters by Dipstick Method
Change from Baseline in vital signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) (Millimeters of mercury)
Change from Baseline in vital sign: Pulse rate (Beats per minute)
Change from Baseline in vital signs: Body temperature (Degrees Celsius)
Change from Baseline in Electrocardiogram (ECG) parameters: PR interval, QRS duration, QT interval and corrected QT (QTc) interval (Milliseconds)
Number of participants with anti-drug antibodies (ADAs) to otilimab
Number of participants with drug-neutralizing antibodies to otilimab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05304130
Brief Title
A Study in Healthy Japanese Participants to Evaluate the Safety and Pharmacokinetics of Otilimab
Official Title
A Single Center, Single Dose, Open-label Study in Healthy Japanese Participants to Evaluate the Safety, Tolerability, and Pharmacokinetics of Otilimab
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Withdrawn
Why Stopped
This study was cancelled because of the limited efficacy demonstrated in the ContRAst phase III programme as a potential treatment for rheumatoid arthritis. GSK has decided not to progress with regulatory submissions
Study Start Date
February 8, 2023 (Anticipated)
Primary Completion Date
May 4, 2023 (Anticipated)
Study Completion Date
May 4, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will assess the safety, tolerability and pharmacokinetics (PK) profiles of otilimab in healthy Japanese participants.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
Japanese participants, Otilimab, Pharmacokinetics, Rheumatoid arthritis, Safety, Tolerability
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Eligible participants will receive treatment with otilimab.
Masking
None (Open Label)
Masking Description
This is an open-label study.
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Healthy Japanese participants receiving otilimab
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Otilimab
Intervention Description
Otilimab will be administered via pre-filled syringe.
Primary Outcome Measure Information:
Title
Maximum drug concentration (Cmax) following administration of otilimab
Time Frame
Up to 8 Weeks
Title
Area under the concentration-time curve from pre-dose to infinity (AUC[0-infinity]) following administration of otilimab
Time Frame
Up to 8 Weeks
Secondary Outcome Measure Information:
Title
Area under the plasma concentration-time curve from pre-dose to t (AUC[0-t]) following administration of otilimab
Time Frame
Up to 8 Weeks
Title
Time to maximum plasma concentration (Tmax) following administration of otilimab
Time Frame
Up to 8 Weeks
Title
Elimination half-life (t1/2) following administration of otilimab
Time Frame
Up to 8 Weeks
Title
Time to reach the last quantifiable plasma concentration (Tlast) following administration of otilimab
Time Frame
Up to 8 Weeks
Title
Number of participants with Adverse events (AEs), Serious adverse events (SAEs) and Adverse events of special interests (AESIs)
Time Frame
Up to 8 weeks
Title
Change from Baseline in hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count (Giga cells per liter)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in hematology parameter: Red blood cell (RBC) count (Trillion cells per liter)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in hematology parameter: Hemoglobin (Grams per Liter)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in hematology parameter: Hematocrit (Proportion of red blood cells in blood)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in hematology parameter: Mean Corpuscular Volume (MCV) (Femtoliters)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in hematology parameter: Mean corpuscular hemoglobin (MCH) (Picograms)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in hematology parameter: Percentage of reticulocytes (Percentage of reticulocytes)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in clinical chemistry parameters: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Creatine kinase, Gamma Glutamyl transferase (GGT), Lactate Dehydrogenase (International units per Liter)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in clinical chemistry parameters: Calcium, glucose, potassium, sodium, Chloride, Phosphate and Blood urea nitrogen (BUN) (Millimoles per Liter)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in clinical chemistry parameters: Creatinine, direct bilirubin, total bilirubin and uric acid (Micromoles per liter)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in clinical chemistry parameters: Albumin and Total protein (Grams per liter)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in clinical chemistry parameter: C-reactive protein (CRP) (Milligrams per liter
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in clinical chemistry parameter: Amylase (Units per liter)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in lipid panel parameters: Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides (Millimoles per Liter)
Time Frame
Baseline and up to 8 weeks
Title
Number of participants with abnormal urinalysis parameters by Dipstick Method
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in vital signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) (Millimeters of mercury)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in vital sign: Pulse rate (Beats per minute)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in vital signs: Body temperature (Degrees Celsius)
Time Frame
Baseline and up to 8 weeks
Title
Change from Baseline in Electrocardiogram (ECG) parameters: PR interval, QRS duration, QT interval and corrected QT (QTc) interval (Milliseconds)
Time Frame
Baseline and up to 8 weeks
Title
Number of participants with anti-drug antibodies (ADAs) to otilimab
Time Frame
Up to Week 8
Title
Number of participants with drug-neutralizing antibodies to otilimab
Time Frame
Up to Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria:
Participant must be 20 to 50 years of age inclusive, at the time of signing the informed consent.
Japanese participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
A Coronavirus Disease-2019 (COVID-19) screening with negative test: Two consecutive approved molecular tests (Polymerase chain reaction [PCR] or antigen test) separated by greater than (>)24 hours. The second test should be within 72 hours of admission to the unit on Day -1.
Body mass index (BMI) within the range 18.5 to 24.9 kilograms per meter square (kg/m^2) (inclusive).
Exclusion Criteria:
History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
Active infections (including localized infections), or history of recurrent infections (excluding recurrent fungal infections of the nail bed), or has required management of acute or chronic infections
History of any respiratory disease which (in the opinion of the investigator) would compromise participant safety or the ability of the participant to complete the study.
Clinically-significant or unstable (in the opinion of the investigator) persistent cough or dyspnea that is unexplained.
Current or previous active Tuberculosis (TB), history of untreated or incompletely treated active or latent TB, suspected or known extra pulmonary TB.
Previous close contact with a person with active TB and did not receive satisfactory anti-tuberculosis treatment as per World Health Organization (WHO) or national guidelines.
Hemoglobin less than or equal to (<=)9 grams per deciliter (g/dL); white blood cell (WBC) count <=3.0 times 10^9/ Liter (L); platelet count <=100 times 10^9/L; absolute neutrophil count (ANC) <=1.0 times 10^9/L; lymphocyte count <=0.75 times 10^9/L at screening.
A vaccination (live or attenuated) within 30 days prior to Day 1 or Bacillus Calmette-Guerin (BCG) vaccination within 365 days prior to Day 1, or a live vaccination planned during the course of the study. Any COVID-19 vaccination within 14 days prior to enrolment.
Any surgical procedure, including bone or joint surgery/synovectomy within 8 weeks prior to Day 1 or any planned surgery within the duration of the study.
Significant allergies to humanized Monoclonal antibody (mAb).
Participants with known COVID-19 positive contacts within 14 days prior to screening.
History of lymphoma, leukemia, or any malignancy.
History of infected joint prosthesis at any time, with the prosthesis still in situ. History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections.
Use of prescription or non-prescription drugs within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study intervention until completion of the evaluation visit, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.
Treatment with biologic agents (such as mAb including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
Blood donation/sampling within 60 days prior to screening.
The participant with positive Serological test for syphilis, Human immunodeficiency virus (HIV) antigen/antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody.
The participant with positive test for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis B surface antibody (HBsAb), or Hepatitis C virus (HCV) antibody.
Positive pre-study drug/alcohol screen.
Participants with signs and symptoms suggestive of COVID-19 (fever, cough) within 14 days prior inpatient admission on Day -1.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
http://clinicalstudydatarequest.com
Learn more about this trial
A Study in Healthy Japanese Participants to Evaluate the Safety and Pharmacokinetics of Otilimab
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