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

Biogen

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer

Treatments: Drug: BIIB113-Matching Placebo; Drug: 11^C]BIO-1819578; Drug: BIIB113

Study type: Interventional

Funder types: Industry

Identifiers

NCT05195008

2021-002903-36 (EudraCT Number)

276HV101

Details and patient eligibility

About

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.

Full description

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

Enrollment: 72 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Key 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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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72 participants in 13 patient groups, including a placebo group

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

Experimental group

Description:

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.

Treatment:

Drug: BIIB113

Part A (SAD): BIIB113 Cohort 2

Experimental group

Description:

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

Treatment:

Drug: BIIB113

Part A (SAD): BIIB113 Cohort 3

Experimental group

Description:

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

Treatment:

Drug: BIIB113

Part A (SAD): BIIB113 Cohort 4

Experimental group

Description:

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

Treatment:

Drug: BIIB113

Part A (SAD): BIIB113 Cohort 5

Experimental group

Description:

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

Treatment:

Drug: BIIB113

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

Placebo Comparator group

Description:

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

Treatment:

Drug: BIIB113-Matching Placebo

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

Experimental group

Description:

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

Treatment:

Drug: BIIB113

Part B (MAD): BIIB113 Cohort 7

Experimental group

Description:

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.

Treatment:

Drug: BIIB113

Part B (MAD): BIIB113 Cohort 8

Experimental group

Description:

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.

Treatment:

Drug: BIIB113

Part B (MAD): BIIB113 Cohort 9

Placebo Comparator group

Description:

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.

Treatment:

Drug: BIIB113

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

Placebo Comparator group

Description:

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

Treatment:

Drug: BIIB113-Matching Placebo

Part C (OGA-PET SAD): BIIB113

Experimental group

Description:

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.

Treatment:

Drug: BIIB113

Drug: 11^C]BIO-1819578

Part C (OGA-PET MAD): BIIB113

Experimental group

Description:

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.

Treatment:

Drug: BIIB113

Drug: 11^C]BIO-1819578