An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
(VALOR (Part C) Trial)

Recruiting in Palo Alto (17 mi)

+39 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Biogen

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The primary objectives of Parts A and B of this study are to evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending doses of tofersen in adults with ALS and a documented superoxide dismutase 1 (SOD1) mutation. The primary objective of Part C of this study is to evaluate the clinical efficacy of tofersen administered to adults with ALS and a confirmed SOD1 mutation. The secondary objective of Parts A and B of this study is to evaluate the effects of tofersen on levels of total SOD1 protein in the cerebrospinal fluid (CSF). The secondary objectives of Part C are to evaluate the safety, tolerability, pharmacodynamic (PD), and biomarker effects of tofersen.

Eligibility Criteria

Inclusion Criteria

Key Inclusion Criteria: Part A and B

Weakness attributable to ALS and documented SOD1 mutation at Screening Visit 2.

A forced vital capacity (FVC) ≥50% of predicted value as adjusted for sex, age, and height (from the sitting position). Participants with stable FVC <50% but ≥45%, whose FVC has not declined by more than 5% in the last 6 months may be considered for inclusion, at the discretion of the Investigator.

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Treatment Details

Interventions

BIIB067 (Antisense Oligonucleotide)
Placebo (Other)

Participant Groups

12Treatment groups

Experimental Treatment

Placebo Group

Group I: Part C-Pivotal: Tofersen 100 mgExperimental Treatment1 Intervention

Participants will be administered tofersen 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.

Group II: Part B-MAD: Cohort 8: Tofersen 100 mgExperimental Treatment1 Intervention

Participants will be administered tofersen 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.

Group III: Part B-MAD: Cohort 7: Tofersen 60 mgExperimental Treatment1 Intervention

Participants will be administered tofersen 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.

Group IV: Part B-MAD: Cohort 6: Tofersen 40 mgExperimental Treatment1 Intervention

Participants will be administered tofersen 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.

Group V: Part B-MAD: Cohort 5: Tofersen 20 mgExperimental Treatment1 Intervention

Participants will be administered tofersen 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.

Group VI: Part A-SAD: Cohort 4: Tofersen 60 mgExperimental Treatment1 Intervention

Participants will be administered tofersen 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.

Group VII: Part A-SAD: Cohort 3: Tofersen 40 mgExperimental Treatment1 Intervention

Participants will be administered tofersen 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.

Group VIII: Part A-SAD: Cohort 2: Tofersen 20 mgExperimental Treatment1 Intervention

Participants will be administered tofersen 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.

Group IX: Part A-SAD: Cohort 1: Tofersen 10 mgExperimental Treatment1 Intervention

Participants will be administered tofersen 10 mg once by intrathecal bolus injection on Day 1.

Group X: Part C-Pivotal: PlaceboPlacebo Group1 Intervention

Participants will be administered tofersen-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.

Group XI: Part A-SAD: Combined PlaceboPlacebo Group1 Intervention

Participants will be administered tofersen-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.

Group XII: Part B-MAD: Combined PlaceboPlacebo Group1 Intervention

Participants will be administered tofersen-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.