- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03070119
Long-Term Evaluation of BIIB067 (Tofersen)
May 19, 2023 updated by: Biogen
An Extension Study to Assess the Long-Term Safety, Tolerability, Pharmacokinetics, and Effect on Disease Progression of BIIB067 Administered to Previously Treated Adults With Amyotrophic Lateral Sclerosis Caused by Superoxide Dismutase 1 Mutation
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.
Study Overview
Status
Active, not recruiting
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
138
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Leuven, Belgium, 3000
- Research Site
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Alberta
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Calgary, Alberta, Canada, T2N 4Z6
- Research Site
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Edmonton, Alberta, Canada, T6G 2B7
- Research Site
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Ontario
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Toronto, Ontario, Canada, M4N 3M5
- Research Site
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Quebec
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Montreal, Quebec, Canada, H3A2B4
- Research Site
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Puy De Dome
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Clermont-Ferrand cedex, Puy De Dome, France, 63003
- Research Site
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Baden Wuerttemberg
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Ulm, Baden Wuerttemberg, Germany, 89081
- Research Site
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Torino, Italy, 10126
- Research Site
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Bunkyo-ku, Japan
- Research Site
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Kagoshima-shi, Japan
- Research Site
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Shinjuku-ku, Japan
- Research Site
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Suita-shi, Japan
- Research Site
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Christchurch, New Zealand, 8011
- Research Site
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South Yorkshire
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Sheffield, South Yorkshire, United Kingdom, S102HQ
- Research Site
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Arizona
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Phoenix, Arizona, United States, 85013
- Research Site
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California
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La Jolla, California, United States, 92093-0949
- Research Site
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San Francisco, California, United States, 94118
- Research Site
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Florida
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Jacksonville, Florida, United States, 32224
- Research Site
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Miami, Florida, United States, 33136
- Research Site
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Orlando, Florida, United States, 32806
- Research Site
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Georgia
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Atlanta, Georgia, United States, 30322
- Research Site
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Illinois
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Chicago, Illinois, United States, 60611
- Research Site
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Maryland
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Baltimore, Maryland, United States, 21287
- Research Site
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Research Site
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Minnesota
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Rochester, Minnesota, United States, 55905
- Research Site
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Missouri
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Saint Louis, Missouri, United States, 63110
- Research Site
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Nebraska
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Lincoln, Nebraska, United States, 68510
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Ohio
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Cleveland, Ohio, United States, 44106
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Oregon
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Portland, Oregon, United States, 97213
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Tennessee
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Knoxville, Tennessee, United States, 37920
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Key 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 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: BIIB067
Participants who have completed Parts A, B, or C of study 233AS101 will be placed in this arm.
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Participants will receive a loading dose regimen followed by maintenance dosing.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Week 364
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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.
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Up to Week 364
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Levels of BIIB067 in Plasma
Time Frame: Up to Week 364
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Up to Week 364
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Levels of BIIB067 in Cerebrospinal Fluid (CSF)
Time Frame: Up to Week 360
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Up to Week 360
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Change from Baseline in Total SOD1 Protein in CSF
Time Frame: Baseline to Week 360
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Baseline to Week 360
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Change from Baseline in Neurofilament Light Chain (NfL) Concentration in Plasma
Time Frame: Baseline to Week 364
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Baseline to Week 364
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Change from Baseline in Total ALS Functional Rating Scale - Revised (ALSFRS-R) Score
Time Frame: Baseline to Week 364
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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.
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Baseline to Week 364
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Change from Baseline in Slow Vital Capacity (SVC)
Time Frame: Baseline to Week 364
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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.
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Baseline to Week 364
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Change from Baseline in Handheld Dynamometry (HHD) Megascore and Individual Muscle Strength
Time Frame: Baseline to Week 364
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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.
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Baseline to Week 364
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Time to Death or Permanent Ventilation
Time Frame: Up to Week 364
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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].
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Up to Week 364
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Time to Death
Time Frame: Up to Week 364
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Up to Week 364
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Medical Director, Biogen
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 8, 2017
Primary Completion (Anticipated)
June 13, 2024
Study Completion (Anticipated)
June 13, 2024
Study Registration Dates
First Submitted
February 28, 2017
First Submitted That Met QC Criteria
February 28, 2017
First Posted (Actual)
March 3, 2017
Study Record Updates
Last Update Posted (Actual)
May 22, 2023
Last Update Submitted That Met QC Criteria
May 19, 2023
Last Verified
May 1, 2023
More Information
Terms related to this study
Other Study ID Numbers
- 233AS102
- 2016-003225-41 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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