Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BIIB107 in Healthy Adult Participants

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04593121
• Other study ID #: 271HV101
• Status: Completed
• Phase: Phase 1
• Start date: October 30, 2020
• Est. completion date: March 5, 2024

Study information

• Verified date: April 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

BIIB107 is a monoclonal antibody (mAb) that targets alpha-4 integrins and is currently in development for people with multiple sclerosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: March 5, 2024
• Est. primary completion date: March 5, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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-a4 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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• BIIB107
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
United States	CenExel Anaheim Clinical Trials	Anaheim	California
United States	QPS MRA (Miami Research Associates)	Miami	Florida
United States	Altasciences Clinical Research	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs): Single Ascending Dose (SAD)	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.	Day -1 up to Day 84
Primary	Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs): Multiple Ascending Dose (MAD)	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.	Day -1 up to Day 169
Secondary	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
Secondary	Maximum Observed Concentration (Cmax): SAD		Day 1 pre-dose and multiple time-points up to Day 84
Secondary	Time to Reach Maximum Observed Concentration (Tmax): SAD		Day 1 pre-dose and multiple time-points up to Day 84
Secondary	Terminal Half-Life (t1/2): SAD		Day 1 pre-dose and multiple time-points up to Day 84
Secondary	Clearance (CL) for IV Doses: SAD		Day 1 pre-dose and multiple time-points up to Day 84
Secondary	Apparent Clearance (CL/F) of SC Doses: SAD		Day 1 pre-dose and multiple time-points up to Day 84
Secondary	Volume of Distribution at Steady State (Vss) for IV Doses: SAD		Day 1 pre-dose and multiple time-points up to Day 84
Secondary	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
Secondary	Bioavailability (F) of SC Doses: SAD		Day 1 pre-dose and multiple time-points up to Day 84
Secondary	Absorption Rate Profile of SC Doses: SAD		Day 1 pre-dose and multiple time-points up to Day 84
Secondary	Maximum Observed Concentration (Cmax): MAD		Day 1 pre-dose and multiple time-points up to Day 169
Secondary	Time to Reach Maximum Observed Concentration (Tmax): MAD		Day 1 pre-dose and multiple time-points up to Day 169
Secondary	Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau): MAD		Day 1 pre-dose and multiple time-points up to Day 169
Secondary	Trough Concentration (Ctrough): MAD		Day 1 pre-dose and multiple time-points up to Day 169
Secondary	Terminal Half-Life (t1/2): MAD		Day 1 pre-dose and multiple time-points up to Day 169
Secondary	Accumulation Ratio (R): MAD		Day 1 pre-dose and multiple time-points up to Day 169
Secondary	Apparent Clearance (CL/F) of SC Doses: MAD		Day 1 pre-dose and multiple time-points up to Day 169
Secondary	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