A Phase 1, Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending-Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB107 in Healthy Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- BIIB107
- Conditions
- Healthy Volunteers
- Sponsor
- Biogen
- Enrollment
- 84
- Locations
- 3
- Primary Endpoint
- Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs): Single Ascending Dose (SAD)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The primary objective is to determine the safety and tolerability of single and multiple ascending subcutaneous (SC) doses and a single intravenous (IV) dose of BIIB107 in healthy adult participants. The secondary objectives are to characterize the single-dose pharmacokinetic (PK) of SC and IV BIIB107 in healthy adult participants and to characterize the multiple-dose PK of SC BIIB107 in healthy adult participants.
Detailed Description
BIIB107 is a monoclonal antibody (mAb) that targets alpha-4 integrins and is currently in development for people with multiple sclerosis.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must have a body mass index (BMI) between 18 and 30 kilogram per meter square (kg/m\^2), inclusive, and must weigh at least 55 kilogram (kg)
- •All women of childbearing potential must practice highly effective contraception during the study and for a period of 90 days, which is expected to be more than 5 half-lives of BIIB
- •Men must practice effective contraception during the study and for a period of 5 half-lives of BIIB107 or 90 days after their last dose of study treatment. In addition, participants should not donate sperm or eggs during the study and for at least 5 half-lives of BIIB107 or 90 days after their last dose of study treatment
- •Negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction test at Screening and Check-in/admission.
Exclusion Criteria
- •History of or positive test result at Screening for human immunodeficiency virus (HIV-1/HIV-2) antibodies
- •Positive test result at Screening for hepatitis C virus (HCV) antibody (Ab).
- •Current hepatitis B infection (defined as per protocol) and participants with immunity to hepatitis B from previous natural infection (defined as negative hepatitis B surface antigen \[HBsAg\], positive hepatitis B surface antibody \[HBsAb\], and positive total hepatitis B core antibody \[HBcAb\]).
- •Signs of active herpes simplex type 1 and 2 or varicella within 4 weeks prior to randomization
- •Evidence of current SARS-CoV-2 infection within 4 weeks prior to Screening, at Screening, between Screening and inpatient admission (Day -1), or at admission (Day -1), including but not limited to a fever (temperature \>37.5°C), new and persistent cough, breathlessness, or loss of taste or smell, per the judgement of the Investigator.
- •Close contact with an individual with coronavirus disease 2019 (COVID-19) infection within 14 days prior to admission (Day -1). Close contact is defined as being within 6 feet of an infected person as confirmed via laboratory assessment for at least 15 minutes within 2 days of symptom onset (or within 2 days of specimen collection for COVID-19 testing for close contact with asymptomatic person).
- •History of tuberculosis (TB) or positive QuantiFERON® TB Gold test or, if the QuantiFERON TB Gold test is not available, a positive purified protein derivative (PPD/Mantoux test; positive PPD/Mantoux test is defined as ≥5 millimeter (mm) of induration \[size of raised lump, not redness\])
- •John Cunningham virus (JCV) seropositivity at Screening (for potential participants enrolling in Part B)
- •Ongoing or past malignancy, carcinoma in situ, or high-grade dysplasia (with the exception of no more than 1 basal cell carcinoma or squamous cell carcinoma that was completely excised and cured at least 12 months prior to randomization)
- •History of severe allergic or anaphylactic reactions or history of allergic reactions that, in the opinion of the Investigator, is likely to be exacerbated by any component of the study treatment.
Arms & Interventions
Cohort 1A
Participants will receive Dose 1 of BIIB107 or placebo subcutaneous (SC) on Day 1.
Intervention: BIIB107
Cohort 1A
Participants will receive Dose 1 of BIIB107 or placebo subcutaneous (SC) on Day 1.
Intervention: Placebo
Cohort 2A
Participants will receive Dose 2 of BIIB107 or placebo SC on Day 1.
Intervention: BIIB107
Cohort 2A
Participants will receive Dose 2 of BIIB107 or placebo SC on Day 1.
Intervention: Placebo
Cohort 3A
Participants will receive Dose 3 of BIIB107 or placebo SC on Day 1.
Intervention: BIIB107
Cohort 3A
Participants will receive Dose 3 of BIIB107 or placebo SC on Day 1.
Intervention: Placebo
Cohort 4A
Participants will receive Dose 4 of BIIB107 or placebo SC on Day 1.
Intervention: BIIB107
Cohort 4A
Participants will receive Dose 4 of BIIB107 or placebo SC on Day 1.
Intervention: Placebo
Cohort 7A
Participants will receive Dose 5 of BIIB107 or placebo SC on Day 1.
Intervention: BIIB107
Cohort 7A
Participants will receive Dose 5 of BIIB107 or placebo SC on Day 1.
Intervention: Placebo
Cohort 5A
Participants will receive Dose 5 of BIIB107 or placebo intravenous (IV) on Day 1.
Intervention: BIIB107
Cohort 5A
Participants will receive Dose 5 of BIIB107 or placebo intravenous (IV) on Day 1.
Intervention: Placebo
Cohort 8A
Participants will receive Dose 6 of BIIB107 or placebo SC on Day 1.
Intervention: BIIB107
Cohort 8A
Participants will receive Dose 6 of BIIB107 or placebo SC on Day 1.
Intervention: Placebo
Cohort 1B
Participants will receive multiple doses of BIIB107 or placebo SC on approximately 4 dosing days.
Intervention: BIIB107
Cohort 1B
Participants will receive multiple doses of BIIB107 or placebo SC on approximately 4 dosing days.
Intervention: Placebo
Cohort 2B
Participants will receive multiple doses of BIIB107 or placebo SC on approximately 4 dosing days.
Intervention: BIIB107
Cohort 2B
Participants will receive multiple doses of BIIB107 or placebo SC on approximately 4 dosing days.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs): Single Ascending Dose (SAD)
Time Frame: Day -1 up to Day 84
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event.
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs): Multiple Ascending Dose (MAD)
Time Frame: Day -1 up to Day 169
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event.
Secondary Outcomes
- Area Under the Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUCinf): SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Maximum Observed Concentration (Cmax): SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Time to Reach Maximum Observed Concentration (Tmax): SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Terminal Half-Life (t1/2): SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Clearance (CL) for IV Doses: SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Apparent Clearance (CL/F) of SC Doses: SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Volume of Distribution at Steady State (Vss) for IV Doses: SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) for SC Doses: SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Bioavailability (F) of SC Doses: SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Absorption Rate Profile of SC Doses: SAD(Day 1 pre-dose and multiple time-points up to Day 84)
- Maximum Observed Concentration (Cmax): MAD(Day 1 pre-dose and multiple time-points up to Day 169)
- Time to Reach Maximum Observed Concentration (Tmax): MAD(Day 1 pre-dose and multiple time-points up to Day 169)
- Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau): MAD(Day 1 pre-dose and multiple time-points up to Day 169)
- Trough Concentration (Ctrough): MAD(Day 1 pre-dose and multiple time-points up to Day 169)
- Terminal Half-Life (t1/2): MAD(Day 1 pre-dose and multiple time-points up to Day 169)
- Accumulation Ratio (R): MAD(Day 1 pre-dose and multiple time-points up to Day 169)
- Apparent Clearance (CL/F) of SC Doses: MAD(Day 1 pre-dose and multiple time-points up to Day 169)
- Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) for SC Doses: MAD(Day 1 pre-dose and multiple time-points up to Day 169)