Long-Term Evaluation of BIIB067 (Tofersen)

Phase 3

Completed

• Conditions: ALS Caused by Superoxide Dismutase 1 (SOD1) Mutation
• Interventions: Drug: Tofersen

• Registration Number: NCT03070119
• Lead Sponsor: Biogen

Brief Summary

The primary objective of the study is to evaluate the long-term safety and tolerability of BIIB067 (tofersen) in participants with amyotrophic lateral sclerosis (ALS) and confirmed superoxide dismutase 1 (SOD1) mutation. The secondary objectives are to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), biomarker effects, and efficacy of BIIB067 administered to participants with ALS and a confirmed SOD1 mutation.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-02-28
• Study First Submitted QC: 2017-02-28
• Study First Posted: 2017-03-03
• Study Start: 2017-03-08
• Status Verified: 2024-08
• Primary Completion: 2024-08-12
• Study Completion: 2024-08-12
• Last Update Submitted: 2024-08-16
• Last Update Posted: 2024-08-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 139

Inclusion Criteria

• Must have diagnosis of superoxide dismutase 1-amyotrophic lateral sclerosis (SOD1-ALS), and must have completed the End of Study Visit for either Parts A, B, or C of Study 233AS101 (NCT02623699) (i.e., were not withdrawn).
• If taking riluzole, participant must be receiving a stable dose for ≥30 days prior to Day 1.
• If taking edaravone, participant must have initiated edaravone ≥60 days (2 treatment cycles) prior to Day 1. Edaravone may not be administered on dosing days during this study.
• Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
• For female participants of childbearing potential must agree to practice effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment.
• Participants from Study 233AS101 Parts A and B must have a washout ≥16 weeks between the last dose of study treatment received in Study 233AS101 and the first dose of BIIB067 received in the current Study 233AS102.

Key

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Exclusion Criteria

• History of allergies to a broad range of anesthetics.
• Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant at an increased risk for bleeding during or after a Lumbar Puncture (LP) procedure. These risks could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand's disease, liver disease).
• Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter.
• Prior or current treatment with small interfering ribonucleic acid (RNA), stem cell therapy, or gene therapy.
• Treatment with another investigational drug, biological agent (excluding BIIB067), or device within 1 month or 5 half-lives of study agent, whichever is longer.
• Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system (DPS) during the study period.
• Current or recent (within 1 month) use, or anticipated need, in the opinion of the Investigator, of copper (II) (diacetyl-bis(N4-methylthiosemicarbazone)) or pyrimethamine.
• Female participants who are pregnant or currently breastfeeding.
• Current enrollment in any other interventional study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BIIB067	Tofersen	Participants who have completed Parts A, B, or C of study 233AS101 will be placed in this arm.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to Week 364	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, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in Slow Vital Capacity (SVC)	Baseline to Week 364	Vital capacity will be measured by means of an SVC test, administered in the upright position. Upright SVC will be determined by performing 3 to 5 measures, in accordance with criteria established by the American Thoracic Society and the European Respiratory Society.
Levels of BIIB067 in Plasma	Up to Week 364
Change from Baseline in Neurofilament Light Chain (NfL) Concentration in Plasma	Baseline to Week 364
Change from Baseline in Handheld Dynamometry (HHD) Megascore and Individual Muscle Strength	Baseline to Week 364	Quantitative muscle strength will be evaluated using HHD, which tests isometric strength of multiple muscles using standard participant positioning. Approximately 8 muscle groups will be examined (per each side) in both upper and lower extremities.
Time to Death or Permanent Ventilation	Up to Week 364	Time to death or permanent ventilation is defined as the time to the earliest occurrence of one of the following events: Death; Permanent ventilation \[≥22 hours of mechanical ventilation (invasive or noninvasive) per day for ≥21 consecutive days\].
Time to Death	Up to Week 364
Levels of BIIB067 in Cerebrospinal Fluid (CSF)	Up to Week 360
Change from Baseline in Total SOD1 Protein in CSF	Baseline to Week 360
Change from Baseline in Total ALS Functional Rating Scale - Revised (ALSFRS-R) Score	Baseline to Week 364	The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 to 4, for a total possible score of 48, with higher scores representing better function.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sheffield, South Yorkshire, United Kingdom