A Study of BIIB067 When Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation

JRCT ID: jRCT2071210032

Registered date:09/06/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Amyotrophic Lateral Sclerosis Associated With a SOD1 Gene Mutation
• Date of first enrollment: 24/12/2021
• Target sample size: 150
• Countries of recruitment: United States,Japan,Canada,Japan,United Kingdom,Japan,Sweden,Japan,Spain,Japan
• Study type: Interventional

Intervention(s)

No Intervention: Part A: Natural History Run-in
Participants enrolled in Part A will undergo blood draws approximately once every 28 days to assess neurofilament light chain (NfL) levels.

Part B: Randomized, Double-Blind, Placebo-Controlled
Participants from Part A who meet the protocol-defined NfL threshold and remain presymptomatic may be eligible to participate in Part B. During Part B, participants will receive BIIB067 100 milligram (mg) or placebo via intrathecal (IT) injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.

Part C: Open-Label Extension
Participants from Part B who develop clinically manifested ALS may be eligible to participate in Part C. During Part C, participants who received placebo in Part B will receive BIIB067 100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years. Participants who received BIIB067 during Part B will receive BIIB067 100 mg on Days 1, 29, and every 28 days thereafter for up to 2 years, with a dose of placebo on Day 15 to maintain the study blind.

Part D: Randomized, Double-Blind, Placebo-Controlled
Participants from Part A who develop clinically manifested ALS prior to randomization in Part B may be eligible to participate in Part D. During Part D, participants will be randomized to receive BIIB067 100 mg or placebo via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.

Outcome(s)

Primary Outcome

Parts B and C:
Percentage of Participants with Emergence of Clinically Manifested ALS Within 1 Year of Part B Baseline

Secondary Outcome

Parts B and C:
- Percentage of Participants with Emergence of Clinically Manifested ALS Within 2 Years of Part B Baseline
- Time to Emergence of Clinically Manifested ALS
- Change in Revised ALS Functional Rating Scale (ALSFRS-R) Total Score
- Change from Baseline in Percent Predicted Slow Vital Capacity (SVC)
- Percentage of Participants with Ventilation Assistance-free Survival (VAFS)
VAFS is defined as time to the earliest occurrence of 1 of the following events:
* Death
* Permanent ventilation. (Permanent ventilation is defined as >= 22 hours of mechanical ventilation [invasive or noninvasive] per day for >= 21 consecutive days.)
- Percentage of Participants with Overall Survival

Parts B, C and D:
- Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the Treatment Period
- Change from Baseline in Plasma NfL Concentrations
- Change in Total Cerebrospinal Fluid (CSF) SOD1 Concentrations

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Key Part A Inclusion Criteria:

- Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is adjudicated for inclusion by an external mutation adjudication committee.

- Participants with plasma NfL level less than the protocol-defined threshold.

- Participants who are clinically presymptomatic for ALS (i.e., must not have clinically manifested ALS).

NOTE: Other protocol defined Inclusion criteria will apply.

Exclude criteria

Key Part A Exclusion Criteria:

- History or positive test result at screening for human immunodeficiency virus (HIV). The requirement for testing at Screening may be omitted if it is not permitted by local regulations.

- Current hepatitis C infection (defined as positive Hepatitis C Virus (HCV) antibody and detectable HCV RNA). Participants with positive HCV antibody and undetectable HCV Ribonucleic Acid (RNA) are eligible to participate in the study (United States Centers for Disease Control and Prevention).

- Current hepatitis B infection (defined as positive for hepatitis B surface antigen (HBsAg) and/or anti-Hepatitis B Core antibody (HBc)). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-hepatitis B surface antibody (HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.

- History of systemic hypersensitivity reaction to BIIB067, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study.

- History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in NF, in the opinion of the Investigator.

- Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that if not managed optimally could place a participant at an increased risk for intraoperative or postoperative bleeding.

- Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression <= 90 days of Screening, which in the opinion of the Investigator would interfere with the study procedures.

- Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication (e.g., clopidogrel) that cannot be safely continued or held for an LP procedure, if necessary, according to local or institutional guidelines and/or Investigator determination.

- Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed.

- Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment, biological agent, device, or approved therapy for investigational use. Participation in a noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator.

NOTE: Other protocol defined Exclusion criteria will apply.

Related Information

• Primary Sponsor: Wong Janice
• Secondary ID(s): NCT04856982