Clinical trial NCT04593121: Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BIIB107 in Healthy Adult Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2020-10-19
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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 BIIB107. 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.

Key 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.
* Any prior exposure to mAbs, Fc-fusion proteins, or the following immunomodulator therapies per investigator judgement: natalizumab or any other anti-α4 integrin antibodies, anti-CD20, sphingosine-1-phosphate receptor modulators, or fumarate therapies.
* Any previous exposure to immunosuppressants (in particular mitoxantrone, methotrexate, azathioprine, cyclophosphamide, and mycophenolate mofetil). Any corticosteroid use should be discussed with the Sponsor prior to enrollment
* Part B only: Women of childbearing potential.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs): Single Ascending Dose (SAD)
timeFrame: Day -1 up to Day 84
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs): Multiple Ascending Dose (MAD)
timeFrame: Day -1 up to Day 169
Secondary outcomes:
measure: Area Under the Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUCinf): SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Maximum Observed Concentration (Cmax): SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Time to Reach Maximum Observed Concentration (Tmax): SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Terminal Half-Life (t1/2): SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Clearance (CL) for IV Doses: SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Apparent Clearance (CL/F) of SC Doses: SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Volume of Distribution at Steady State (Vss) for IV Doses: SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) for SC Doses: SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Bioavailability (F) of SC Doses: SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Absorption Rate Profile of SC Doses: SAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 84
measure: Maximum Observed Concentration (Cmax): MAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 169
measure: Time to Reach Maximum Observed Concentration (Tmax): MAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 169
measure: Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau): MAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 169
measure: Trough Concentration (Ctrough): MAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 169
measure: Terminal Half-Life (t1/2): MAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 169
measure: Accumulation Ratio (R): MAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 169
measure: Apparent Clearance (CL/F) of SC Doses: MAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 169
measure: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) for SC Doses: MAD
timeFrame: Day 1 pre-dose and multiple time-points up to Day 169
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: CenExel Anaheim Clinical Trials
state: California
city: Miami
country: United States
facility: QPS MRA (Miami Research Associates)
state: Florida
city: Overland Park
country: United States
facility: Altasciences Clinical Research
state: Kansas
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: