Clinical trial NCT03070119: Long-Term Evaluation of BIIB067 (Tofersen)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ALS Caused by Superoxide Dismutase 1 (SOD1) Mutation
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2017-03-03
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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must have completed the End of Study Visit for either Parts A, B, or C of Study 233AS101 (NCT02623699) (i.e., were not withdrawn).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

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 364
Secondary outcomes:
measure: Levels of BIIB067 in Plasma
timeFrame: Up to Week 364
measure: Levels of BIIB067 in Cerebrospinal Fluid (CSF)
timeFrame: Up to Week 360
measure: Change from Baseline in Total SOD1 Protein in CSF
timeFrame: Baseline to Week 360
measure: Change from Baseline in Neurofilament Light Chain (NfL) Concentration in Plasma
timeFrame: Baseline to Week 364
measure: Change from Baseline in Total ALS Functional Rating Scale - Revised (ALSFRS-R) Score
timeFrame: Baseline to Week 364
measure: Change from Baseline in Slow Vital Capacity (SVC)
timeFrame: Baseline to Week 364
measure: Change from Baseline in Handheld Dynamometry (HHD) Megascore and Individual Muscle Strength
timeFrame: Baseline to Week 364
measure: Time to Death or Permanent Ventilation
timeFrame: Up to Week 364
measure: Time to Death
timeFrame: Up to Week 364
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: La Jolla
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Leuven
country: Belgium
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Clermont-Ferrand cedex
country: France
facility: Research Site
state: Puy De Dome
city: Ulm
country: Germany
facility: Research Site
state: Baden Wuerttemberg
city: Torino
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Suita-shi
country: Japan
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
state: South Yorkshire
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.