Long-Term Evaluation of BIIB067 (Tofersen)

NCT03070119 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 233AS1022016-003225-41
• Study Type: interventional
• Target: 139
• Locations: 9 countries
• Sites: 30

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.

Conditions

ALS Caused by Superoxide Dismutase 1 (SOD1) Mutation

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)

  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. TEAEs were defined as any AEs or SAE with an onset date and time that was on or after the first dose of study drug, or any pre-existing condition that worsened in severity after the first dose of study drug.

  From first dose of the study drug in the current study up to end of follow-up period (up to Week 364)

Secondary Outcomes (10)

• Plasma Concentration of BIIB067

  Week 4

• Concentration of BIIB067 in Cerebrospinal Fluid (CSF)

  Week 4

• 233AS101 and 233AS102 Integrated Summary of Efficacy (ISE): Total CSF Superoxide Dismutase 1 (SOD1) Protein Ratio to Baseline

  Baseline, Weeks 52, 104 and 148

• 233AS101 and 233AS102 ISE: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline

  Baseline, Weeks 52, 104 and 148

• 233AS101 and 233AS102 ISE: Change From Baseline in Total Amyotropic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score

  Baseline, Weeks 52, 104 and 148

Study Arms (1)

BIIB067

EXPERIMENTAL

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

Drug: Tofersen

Interventions

Tofersen DRUG

Participants will receive a loading dose regimen followed by maintenance dosing.

Also known as: BIIB067, QALSODY

BIIB067

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead
• Ionis Pharmaceuticals, Inc.: collaborator

Study Sites (30)

Research Site

Phoenix, Arizona, 85013, United States

Location

Research Site

La Jolla, California, 92093-0949, United States

Location

Research Site

San Francisco, California, 94118, United States

Location

Research Site

Jacksonville, Florida, 32224, United States

Location

Research Site

Miami, Florida, 33136, United States

Location

Research Site

Orlando, Florida, 32806, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Chicago, Illinois, 60611, United States

Location

Research Site

Baltimore, Maryland, 21287, United States

Location

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

Rochester, Minnesota, 55905, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Lincoln, Nebraska, 68510, United States

Location

Research Site

Cleveland, Ohio, 44106, United States

Location

Research Site

Portland, Oregon, 97213, United States

Location

Research Site

Knoxville, Tennessee, 37920, United States

Location

Research Site

Leuven, 3000, Belgium

Location

Research Site

Calgary, Alberta, T2N 4Z6, Canada

Location

Research Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Research Site

Toronto, Ontario, M4N 3M5, Canada

Location

Research Site

Montreal, Quebec, H3A2B4, Canada

Location

Bispebjerg Hospital

Copenhagen, 2400, Denmark

Location

Research Site

Clermont-Ferrand, Puy De Dome, 63003, France

Location

Research Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Research Site

Torino, 10126, Italy

Location

Research Site

Bunkyō City, Japan

Location

Research Site

Kagoshima, Japan

Location

Research Site

Shinjuku-ku, Japan

Location

Research Site

Suita-shi, Japan

Location

Research Site

Sheffield, South Yorkshire, S102HQ, United Kingdom

Location

Related Publications (1)

• Miller TM, Cudkowicz ME, Genge A, Shaw PJ, Sobue G, Bucelli RC, Chio A, Van Damme P, Ludolph AC, Glass JD, Andrews JA, Babu S, Benatar M, McDermott CJ, Cochrane T, Chary S, Chew S, Zhu H, Wu F, Nestorov I, Graham D, Sun P, McNeill M, Fanning L, Ferguson TA, Fradette S; VALOR and OLE Working Group. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2022 Sep 22;387(12):1099-1110. doi: 10.1056/NEJMoa2204705.

  PMID: 36129998 DERIVED

MeSH Terms

Interventions

tofersen

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2017
• First Posted: March 3, 2017
• Study Start: March 8, 2017
• Primary Completion: August 12, 2024
• Study Completion: August 12, 2024
• Last Updated: August 29, 2025
• Results First Posted: August 29, 2025

Record last verified: 2025-08

Locations

US (16); DK (1); IT (1); CA (4); BE (1); DE (1); FR (1); JP (4); GB (1)