A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics, With Target Occupancy Study of BIIB113 in Healthy Participants

NCT ID: NCT05195008

Last Updated: 2024-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-24
• Study Completion Date: 2023-07-10

Brief Summary

Parts A and B: The primary objective of this study is to evaluate the safety and tolerability of single and multiple ascending oral doses of BIIB113 in healthy participants. The secondary objectives of this study are to evaluate the single and multiple oral dose pharmacokinetic (PK) profile of BIIB113 in healthy participants and to evaluate the effect of food on the single oral dose of BIIB113 in healthy participants of Part A cohort 3.

Part C: The primary objectives of this study are to evaluate the safety and tolerability of single and multiple ascending oral doses of BIIB113 in healthy participants and to determine target occupancy (TO) as measured by O-GlcNAcase-Positron Emission Tomography (OGA-PET) of single and multiple oral doses of BIIB113 in healthy participants.

Detailed Description

BIIB113 is a small molecule inhibitor of OGA being evaluated in Alzheimer's disease.

Conditions

Healthy Volunteer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A [Single Ascending Dose (SAD)]: BIIB113 Cohort 1

Participants aged 18 to 64 years will receive Dose 1 of BIIB113, orally, once daily (QD), on Day 1 of Part A of the study.

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part A (SAD): BIIB113 Cohort 2

Participants aged 18 to 64 years will receive Dose 2 of BIIB113, orally, QD, on Day 1 of Part A of the study

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part A (SAD): BIIB113 Cohort 3

Participants aged 18 to 64 years will receive Dose 3 of BIIB113, orally, QD, on Day 1 of Part A of the study.

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part A (SAD): BIIB113 Cohort 4

Participants aged 18 to 64 years will receive Dose 4 of BIIB113, orally, QD, on Day 1 of Part A of the study.

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part A (SAD): BIIB113 Cohort 5

Participants aged 18 to 64 years will receive Dose 5 of BIIB113, orally, QD, on Day 1 of Part A of the study

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part A (SAD): BIIB113-Matching Placebo (Cohorts 1-5)

Participants aged 18 to 64 years will receive BIIB113-matching placebo, orally, QD, on Day 1 of Part A of the study.

Group Type: PLACEBO_COMPARATOR

BIIB113-Matching Placebo

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part B [Multiple Ascending Dose (MAD)]: BIIB113 Cohort 6

Participants aged 18 to 64 years will receive Dose 3 of BIIB113, orally, QD, up to Day 14 of Part B of the study.

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part B (MAD): BIIB113 Cohort 7

Participants aged 18 to 64 years will receive Dose 4 of BIIB113, orally, QD, on Days 1 to 14 of Part B of the study.

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part B (MAD): BIIB113 Cohort 8

Participants aged 18 to 64 years will receive Dose 6 of BIIB113, orally, QD, on Days 1 to 14 of Part B of the study.

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part B (MAD): BIIB113 Cohort 9

Participants aged 65 to 75 years will receive BIIB113, orally, QD, on Days 1 to 14 of Part B of the study. The calculated dose level will be adaptive by design based on review of the safety, tolerability, and PK data from Cohorts 1 to 7.

Group Type: PLACEBO_COMPARATOR

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part B (MAD): BIIB113-Matching Placebo (Cohorts 6 to 9)

Participants aged 18 to 75 will receive BIIB113-matching placebo, orally, QD, on Days 1 to 14 of Part B of the study.

Group Type: PLACEBO_COMPARATOR

BIIB113-Matching Placebo

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part C (OGA-PET SAD): BIIB113

Participants aged 20 to 64 will receive single dose of BIIB113, orally, QD, on Day 1 of Part C of the study, followed by a radiotracer specific to OGA (\[11\^C\]BIO-1819578), on Days 1 to 4 of Part C of the study.

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

11^C]BIO-1819578

Intervention Type: DRUG

Administered as specified in the treatment arm.

Part C (OGA-PET MAD): BIIB113

Participants aged 20 to 64 years will receive multiple doses of BIIB113, orally, QD, on Days 1 to 14 of Part C of the study, followed by a radiotracer specific to OGA (\[11\^C\]BIO-1819578) on Day 1 and either of Day 15, Day 16 or Day 17 of Part C of the study.

Group Type: EXPERIMENTAL

BIIB113

Intervention Type: DRUG

Administered as specified in the treatment arm.

11^C]BIO-1819578

Intervention Type: DRUG

Administered as specified in the treatment arm.

Interventions

BIIB113

Administered as specified in the treatment arm.

Intervention Type: DRUG

BIIB113-Matching Placebo

Administered as specified in the treatment arm.

Intervention Type: DRUG

11^C]BIO-1819578

Administered as specified in the treatment arm.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Female or infertile/vasectomized males aged 18 to 64 years (Parts A and B), 20 to 64 years (Part C), or 65 to 75 years (Part B Dose 7Cohort 9 only), inclusive, at the time of informed consent
• Have a body mass index between 18 and 32 kilograms per square meter (kg/m^2), inclusive, at screening
• Weight ≥50 kilograms (kg) at screening
• Negative Polymerase Chain Reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 5 days of Day -1 prior to randomization

Exclusion Criteria

• History or positive test result at Screening for Human Immunodeficiency Virus (HIV)
• Chronic, recurrent, or serious infection (e.g., pneumonia, septicemia), as determined by the investigator, within 90 days prior to screening or between screening and Day -1
• History of severe allergic or anaphylactic reactions, or of any allergic reactions that in the opinion of the investigator are likely to be exacerbated by any component of the study treatment
• History of systemic hypersensitivity reaction to BIIB113 or the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study
• Has suicidal ideation with some intent to act within 6 months prior to the start of screening, per the investigator's clinical judgment or based on the C-SSRS, corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or a history of suicidal behaviour within one year prior to the start of screening.
• Any condition affecting study treatment absorption (e.g., gastrectomy)
• Previous exposure to an OGA inhibitor
• Current enrolment in any other drug, biologic, device, or clinical study, or treatment with an investigational drug or approved therapy for investigational use within 90 days (6 months for biologics) prior to Day -1, or 5 half-lives of the agent, whichever is longer
• For Part C only: Previously undergone PET scans for research purposes

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

Karolinska Comprehensive Cancer Center - Studieenheten

Flemingsberg, Stockholm County, Sweden

Hammersmith Medicine Research

London, Brent, United Kingdom

Medicines Evaluation Unit

Wythenshawe, Manchester, United Kingdom

Countries

Sweden; United Kingdom

Other Identifiers

2021-002903-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

276HV101

Identifier Type: -

Identifier Source: org_study_id