Clinical trial NCT05195008: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics, With Target Occupancy Study of BIIB113 in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2022-01-18
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Part A: Up to 54 days; Part B: Up to 53 days; Part C: Up to 71 days (SAD); Up to 85 days (MAD)
measure: 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)
timeFrame: 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)
measure: Parts A, B and C: Number of Participants With Change in Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Part A: Up to 54 days; Part B: Up to 53 days; Part C: Up to 71 days (SAD); Up to 85 days (MAD)
measure: Part C: Percent O-GlcNAcase-Positron Emission Tomography (OGA PET) Target Engagement/Occupancy (TO) as a Function of Dose and Time
timeFrame: Up to Day 4 (SAD); Up to Day 17 (MAD)
Secondary outcomes:
measure: Parts A and B: Area Under the Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) of BIIB113
timeFrame: 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
measure: Parts A and B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC∞) of BIIB113
timeFrame: 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
measure: Parts A and B: Area Under the Plasma Concentration-Time Curve Within a Dosing Interval (AUCtau) of BIIB113
timeFrame: 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
measure: Parts A and B: Maximum Observed Concentration (Cmax) for BIIB113
timeFrame: 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
measure: Parts A and B: Trough Concentration (Ctrough) of BIIB113
timeFrame: 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
measure: Parts A and B: Time to Maximum Observed Concentration (Tmax) of BIIB113
timeFrame: 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
measure: Parts A and B: Terminal Elimination Half-Life (t½) of BIIB113
timeFrame: 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
measure: Parts A and B: Apparent Total Body Clearance (CL/F) of BIIB113
timeFrame: 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
measure: Parts A and B: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of BIIB113
timeFrame: 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
measure: Parts A and B: Accumulation Ratio (AR) of BIIB113
timeFrame: 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
measure: Parts A and B: Amount of BIIB113 Excreted in Urine (Aeu)
timeFrame: 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
measure: Parts A and B: Percentage of BIIB113 Excreted in Urine (%fe)
timeFrame: 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
Other outcomes:
Locations:
city: Flemingsberg
country: Sweden
facility: Karolinska Comprehensive Cancer Center - Studieenheten
state: Stockholm
city: London
country: United Kingdom
facility: Hammersmith Medicine Research
state: Brent
city: Wythenshawe
country: United Kingdom
facility: Medicines Evaluation Unit
state: Manchester
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: