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

A Phase 1 Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics, With an Open-Label Target Occupancy Study of BIIB113 in Healthy Participants

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: BIIB113; Drug: BIIB113-Matching Placebo; Drug: 11^C]BIO-1819578

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm
    • Flemingsberg, Stockholm, Sweden, 14186
      • Karolinska Comprehensive Cancer Center - Studieenheten
• United Kingdom
  • Brent
    • London, Brent, United Kingdom, NW10 7EW
      • Hammersmith Medicine Research
  • Manchester
    • Wythenshawe, Manchester, United Kingdom, M23 9QZ
      • Medicines Evaluation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: BIIB113; Administered as specified in the treatment arm.
Experimental: 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	Drug: BIIB113; Administered as specified in the treatment arm.
Experimental: 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.	Drug: BIIB113; Administered as specified in the treatment arm.
Experimental: 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.	Drug: BIIB113; Administered as specified in the treatment arm.
Experimental: 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	Drug: BIIB113; Administered as specified in the treatment arm.
Placebo Comparator: 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.	Drug: BIIB113-Matching Placebo; Administered as specified in the treatment arm.
Experimental: 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.	Drug: BIIB113; Administered as specified in the treatment arm.
Experimental: 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.	Drug: BIIB113; Administered as specified in the treatment arm.
Experimental: 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.	Drug: BIIB113; Administered as specified in the treatment arm.
Placebo Comparator: 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.	Drug: BIIB113; Administered as specified in the treatment arm.
Placebo Comparator: 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.	Drug: BIIB113-Matching Placebo; Administered as specified in the treatment arm.
Experimental: 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.	Drug: BIIB113; Administered as specified in the treatment arm.; Drug: 11^C]BIO-1819578; Administered as specified in the treatment arm.
Experimental: 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.	Drug: BIIB113; Administered as specified in the treatment arm.; Drug: 11^C]BIO-1819578; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant 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; in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); 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.	Part A: Up to 54 days; Part B: Up to 53 days; Part C: Up to 71 days (SAD); Up to 85 days (MAD)
Parts A, B and C: Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters, Vital Signs, and 12-Lead Electrocardiogram (ECG)		Part A: Baseline up to 54 days; Part B: Baseline up to 53 days; Part C: Baseline up to 71 days (SAD), Baseline up to 85 days (MAD)
Parts A, B and C: Number of Participants With Change in Columbia Suicide Severity Rating Scale (C-SSRS) Score	C-SSRS is used to assess the suicidality of participants during the study. The assessment includes "yes" or "no" responses for 5 questions each, related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings are provided for severity of ideation, from 1 to 5, with 5 being the most severe.	Part A: Up to 54 days; Part B: Up to 53 days; Part C: Up to 71 days (SAD); Up to 85 days (MAD)
Part C: Percent O-GlcNAcase-Positron Emission Tomography (OGA PET) Target Engagement/Occupancy (TO) as a Function of Dose and Time		Up to Day 4 (SAD); Up to Day 17 (MAD)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A and B: Area Under the Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) of BIIB113	The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC∞) of BIIB113	The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Area Under the Plasma Concentration-Time Curve Within a Dosing Interval (AUCtau) of BIIB113	The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Maximum Observed Concentration (Cmax) for BIIB113	The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Trough Concentration (Ctrough) of BIIB113	The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Time to Maximum Observed Concentration (Tmax) of BIIB113	The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Terminal Elimination Half-Life (t½) of BIIB113	t1/2 is the time measured for the plasma concentration to decrease by one half. The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Apparent Total Body Clearance (CL/F) of BIIB113	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. If the bioavailability (F) of a dose is assumed to be 100% or equivalently, that clearance is the apparent clearance (CL/F) when the ratio of clearance to bioavailability is assumed to be constant. The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of BIIB113	Volume of distribution is defined as the apparent volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Accumulation Ratio (AR) of BIIB113	The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Amount of BIIB113 Excreted in Urine (Aeu)	The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15
Parts A and B: Percentage of BIIB113 Excreted in Urine (%fe)	The parameter will be assessed under fed conditions for Part A Cohort 3.	Part A: Pre-dose and at multiple timepoints post-dose on Days 1 to 4; Part B: Pre-dose and at multiple timepoints post-dose on Days 1 to 15

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Actual): July 10, 2023
• Study Completion (Actual): July 10, 2023

Study Registration Dates

• First Submitted: January 4, 2022
• First Submitted That Met QC Criteria: January 4, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 276HV101; 2021-002903-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No