biogen/studies/attachments/NCT05195008-LLS_English.pdf

NCT05195008-LLS English

biogen/studies/attachments/NCT05195008-LLS_Swedish_Sweden.pdf

NCT05195008-LLS Swedish (Sweden)

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.

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

Healthy Volunteers

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

BIIB113

BIIB113-Matching Placebo

11^C]BIO-1819578

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

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.

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.

The parameter will be assessed under fed conditions for Part A Cohort 3.

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.

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.

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.

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.

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

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

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

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

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

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

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.

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.

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.

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

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.

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.

Healthy Volunteer

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.

Karolinska Comprehensive Cancer Center - Studieenheten

Hammersmith Medicine Research

Medicines Evaluation Unit

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.

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.

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.

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.

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.

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.

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

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

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

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

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

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

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.

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.

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.

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

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.

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.