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

NCT05195008 | Completed Phase 1

• 2 other identifiers: 276HV1012021-002903-36
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 3

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (12)

• Parts A and B: Area Under the Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) of BIIB113

  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

  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

  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

  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

  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

Study Arms (13)

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

EXPERIMENTAL

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

Part A (SAD): BIIB113 Cohort 2

EXPERIMENTAL

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

Part A (SAD): BIIB113 Cohort 3

EXPERIMENTAL

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

Part A (SAD): BIIB113 Cohort 4

EXPERIMENTAL

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

Part A (SAD): BIIB113 Cohort 5

EXPERIMENTAL

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

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

PLACEBO COMPARATOR

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

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

EXPERIMENTAL

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

Part B (MAD): BIIB113 Cohort 7

EXPERIMENTAL

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

Part B (MAD): BIIB113 Cohort 8

EXPERIMENTAL

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

Part B (MAD): BIIB113 Cohort 9

PLACEBO COMPARATOR

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

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

PLACEBO COMPARATOR

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

Part C (OGA-PET SAD): BIIB113

EXPERIMENTAL

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; Drug: 11^C]BIO-1819578

Part C (OGA-PET MAD): BIIB113

EXPERIMENTAL

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; Drug: 11^C]BIO-1819578

Interventions

BIIB113 DRUG

Administered as specified in the treatment arm.

Part A (SAD): BIIB113 Cohort 2; Part A (SAD): BIIB113 Cohort 3; Part A (SAD): BIIB113 Cohort 4; Part A (SAD): BIIB113 Cohort 5; Part A [Single Ascending Dose (SAD)]: BIIB113 Cohort 1; Part B (MAD): BIIB113 Cohort 7; Part B (MAD): BIIB113 Cohort 8; Part B (MAD): BIIB113 Cohort 9; Part B [Multiple Ascending Dose (MAD)]: BIIB113 Cohort 6; Part C (OGA-PET MAD): BIIB113; Part C (OGA-PET SAD): BIIB113

BIIB113-Matching Placebo DRUG

Administered as specified in the treatment arm.

Part A (SAD): BIIB113-Matching Placebo (Cohorts 1-5); Part B (MAD): BIIB113-Matching Placebo (Cohorts 6 to 9)

11^C]BIO-1819578 DRUG

Administered as specified in the treatment arm.

Part C (OGA-PET MAD): BIIB113; Part C (OGA-PET SAD): BIIB113

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: lead

Study Sites (3)

Karolinska Comprehensive Cancer Center - Studieenheten

Flemingsberg, Stockholm County, 14186, Sweden

Location

Hammersmith Medicine Research

London, Brent, NW10 7EW, United Kingdom

Location

Medicines Evaluation Unit

Wythenshawe, Manchester, M23 9QZ, United Kingdom

Location

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: January 18, 2022
• Study Start: January 24, 2022
• Primary Completion: July 10, 2023
• Study Completion: July 10, 2023
• Last Updated: February 5, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

SE (1); GB (2)