Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of OSE-127 in Healthy Subjects
Study Details
Study Description
Brief Summary
This study is a first-in-human phase I randomised, double-blind, placebo-controlled, evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single (IV and SC) and Multiple (IV only) Ascending Doses of OSE-127 in Healthy Subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: OSE-127: Part 1 (SAD), Cohort A & Cohort B
|
Drug: OSE-127
mAb antagonist to CD127 receptor (or IL-7Rα)
Group 1-7
6 escalating dose level groups IV
SC
|
| Placebo Comparator: Placebo: Part 1 (SAD), Cohort A & Cohort B
|
Drug: Placebo
Vehicle study drug
|
| Experimental: OSE-127: Part 2 (MAD)
|
Drug: OSE-127
mAb antagonist to CD127 receptor (or IL-7Rα)
Group 8-9
2 escalating dose level groups IV
|
| Placebo Comparator: Placebo: Part 2 (MAD)
|
Drug: Placebo
Vehicle study drug
|
Outcome Measures
Primary Outcome Measures
- Part 1 (SAD) & Part 2 (MAD) : Number of Participants With Treatment Emergent Adverse Events (TEAEs) [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Number of Participants With Clinically Significant Findings in Physical Examinations Reported as Adverse Event [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as Adverse Event [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) :Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Adverse Event [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) :Number of Participants With Clinically Significant Change in vital signs Reported as Adverse Event [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) :Number of Participants With Clinically Significant Findings in Telemetry Reported as Adverse Event [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Incidence of anti-drug antibody (ADA) formation [12 weeks (for Part 1); 19 weeks (for Part 2)]
Secondary Outcome Measures
- Part 1 (SAD) & Part 2 (MAD) : Maximum Plasma Concentration [Cmax] [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Average serum Concentration over the dosing interval [Cavg] [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Trough serum Concentration observed at the end of the dosing interval [Ctrough] [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Elimination half-life associated with the terminal rate constant (λz) [T1/2] [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Time corresponding to the Cmax [Tmax] [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Area Under the serum concentration-time Curve from time zero till X days postdose [AUCτ] [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : AUC calculated between time of administration and last quantifiable concentration [AUClast] [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : AUC extrapolated to infinity [AUCinf] [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : AUC over the dosing interval [AUC0-τ]. [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Accumulation Ratio [Rac]. [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : CD-127 Receptor Occupancy [RO] [12 weeks (for Part 1); 19 weeks (for Part 2)]
- Part 1 (SAD) & Part 2 (MAD) : Effect on total lymphocyte count [12 weeks (for Part 1); 19 weeks (for Part 2)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female, aged 18 to 65 years (extremes included). Maximum two subjects aged between 60 and 65 (extremes included) are allowed per dose group.
-
Healthy volunteers (medically stable), as determined on the basis of medical history, vital signs, clinical laboratory testing, and general physical examination performed at screening and deemed appropriate by the Investigator.
-
Electrocardiogram (ECG) within normal range, or showing no clinically relevant deviations, as judged by the Investigator.
-
Weighs at least 50 kg and no more than 100 kg and has a Body Mass Index (BMI) within normal range: 19.0 ≤ BMI ≤ 30.0 kg/m².
-
Negative urine test for selected drugs of abuse at screening.
-
Negative alcohol breath test at screening.
-
Female subjects is postmenopausal, surgically sterile (having had a hysterectomy or bilateral oophorectomy) and/or is using a highly effective method of contraception (from 2 weeks before first study drug administration until 28 days after the last follow-up visit, when it is confirmed that the RO of the subject <20% or 5 t1/2 whichever is longer).
-
Female subject has a negative pregnancy test at screening.
-
Non-vasectomized male subjects having a female partner of childbearing potential must agree to the use of a highly effective method of contraception (from the first study drug administration until 28 days after the last follow-up visit, when it is confirmed that the RO of the subject <20% or 5 t1/2 whichever is longer).
-
Willing to adhere to the prohibitions and restrictions specified in the protocol.
-
Informed Consent Form (ICF) signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study.
-
Non-smoker or light smoker, i.e. smokes maximal 5 cigarettes (or 3 cigars or 3 pipe-full) per day, and ability and willingness to refrain from smoking during confinement and ambulant visits in the CPU.
Exclusion Criteria:
-
A history of any clinically significant (as determined by the Investigator) cardiac, endocrinology, hematology, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy excluding non-melanoma skin cancer.
-
A known allergy, hypersensitivity, or intolerance to any of the excipients in the formulation of the study drug.
-
The subject has a history of severe allergic or anaphylactic reactions.
-
The suject has a history of consuming more than 14 units of alcoholic beverages per week for male subjects, and more than 10 units for females. Or a history of alcoholism, or drug/chemical/substance abuse within the past 2 years prior to screening.
-
Evidence or history of any clinically significant infections within the past 3 months.
-
Subject with known clinically relevant immunological disorders, or auto-immune disorders (e.g. rheumatoid arthritis, lupus erythematosus, scleroderma, etc...).
-
A positive hepatitis panel (including hepatitis B surface antigen [HBsAg] and anti-hepatitis C virus [HCV] antibodies [Abs]) or positive human immunodeficiency virus (HIV) antibody screens.
-
The subject has a supine systolic blood pressure (SBP) <90 or >149 mmHg and/or a diastolic blood pressure (DBP) <45 or >90 mmHg, and/or a pulse rate higher than 100 beats per minute (bpm) at screening (blood pressure measurements taken after subject has been resting in a supine position for a minimum of 5 minutes).
-
Pregnant or breastfeeding women.
-
The subject has received a live vaccine (excluding flu vaccination), within 30 days prior to study drug administration, or plan to receive this type of vaccine during the study.
-
The subject has received any systemic immunosuppressant agent, within 6 months prior to study drug administration.
-
The subject has received any antibody or biologic medicinal product, within 6 months prior to study drug administration.
-
The subject has received any systemic steroid, within 2 months prior to study drug administration.
-
Use of a prohibited therapy during the study.
-
Receipt of any investigational drug, within 30 days or 5 half-lives (whichever is longer) prior to the initial study drug administration.
-
The subject is participating in another clinical trial or has participated in another dose group of the current trial. Participation in non-interventional registries or epidemiological studies is allowed.
-
Having had a significant blood loss (including blood donation [>500 mL]) or a having had a transfusion of any blood product (within the past 60 days) or donated plasma (within 7 days prior to the initial study drug administration).
-
A condition that, in the opinion of the Investigator, could compromise their well-being or the course of the study, or prevent them from meeting or performing any study requirement.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | SGS Life Sciences (SGS LS), Clinical Pharmacology Unit (CPU) | Antwerp | Belgium | 2060 |
Sponsors and Collaborators
- OSE Immunotherapeutics
- Servier
Investigators
- Study Director: Frédérique Corallo, MD, OSE Immunotherapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OSE-127-C101
- 2018-001832-22