Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of OSE-127 in Healthy Subjects

NCT03980080 | Completed Phase 1 DMC

• 2 other identifiers: OSE-127-C1012018-001832-22
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Keywords

CD127/IL-7Rα Antagonist; Auto-Immune Diseases; inflammatory bowel diseases; Ulcerative Colitis

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (12)

• 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)

Study Arms (4)

OSE-127: Part 1 (SAD), Cohort A & Cohort B

EXPERIMENTAL

Drug: OSE-127

Placebo: Part 1 (SAD), Cohort A & Cohort B

PLACEBO COMPARATOR

Drug: Placebo

OSE-127: Part 2 (MAD)

EXPERIMENTAL

Drug: OSE-127

Placebo: Part 2 (MAD)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

OSE-127 DRUG

mAb antagonist to CD127 receptor (or IL-7Rα) Group 1-7 6 escalating dose level groups IV SC

OSE-127: Part 1 (SAD), Cohort A & Cohort B

Placebo DRUG

Vehicle study drug

Placebo: Part 1 (SAD), Cohort A & Cohort B; Placebo: Part 2 (MAD)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• OSE Immunotherapeutics: lead
• Servier: collaborator

Study Sites (1)

SGS Life Sciences (SGS LS), Clinical Pharmacology Unit (CPU)

Antwerp, 2060, Belgium

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Study Officials

• Frédérique Corallo, MD

  OSE Immunotherapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 (SAD) primary objective : safety and tolerability profile of single ascending IV (Cohort A) and SC (Cohort B) doses given to healthy subjects, compared to placebo. Part 2 (MAD) primary objective : safety and tolerability profile of two IV doses given on two separate occasions to healthy subjects, compared to placebo.

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: June 10, 2019
• Study Start: December 19, 2018
• Primary Completion: November 4, 2019
• Study Completion: November 4, 2019
• Last Updated: December 12, 2019

Record last verified: 2019-12

Locations

BE (1)