Study Purpose:
The primary objectives of Parts A and B of this study are to evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending doses of BIIB067 (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 BIIB067 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 BIIB067 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 BIIB067.
Study Status:
Not recruiting
Disease:
Amyotrophic Lateral Sclerosis
Study Type:
Interventional
Type of Intervention:
Drug, N/A
Intervention Name:
BIIB067, Placebo
Placebo:
Yes
Phase:
Phase 3
Study Chair(s)/Principal Investigator(s):
Medical Director, Biogen
Clinicaltrials.gov ID:
Neals Affiliated?
Yes
Coordinating Center Contact Information
Biogen
United States
Full Study Summary:
The study completed on 15 Jul 2021. In total, the study enrolled 178 participants, of which 108 enrolled in Part C.
Study Sponsor:
Biogen
Estimated Enrollment:
178
Estimated Study Start Date:
01 / 20 / 2016
Estimated Study Completion Date:
07 / 16 / 2021
Posting Last Modified Date:
07 / 19 / 2022
Date Study Added to neals.org:
12 / 08 / 2015
Additional information can be found here: www.alsvalorstudy.com
Minimum Age:
18 Years
Maximum Age:
N/A
Can participants use Riluzole?
Yes
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.
- If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit.
- 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.
Key Exclusion Criteria: Part A and B
- History of or positive test result for human immunodeficiency virus.
- History of, or positive test result at Screening, for hepatitis C virus antibody.
- Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive hepatitis B surface antibody immunoglobulin G, and positive HBcAb) or vaccination (defined as positive anti-HBs) are eligible to participate in the study.
- Treatment with another investigational drug, biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering ribonucleic acid, stem cell therapy, or gene therapy is allowed.
- Current enrollment in any other interventional study.
- 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.
- Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system (DPS) during the study period.
Key Inclusion Criteria: Part C
- Weakness attributable to ALS and confirmed SOD1 mutation at Screening Visit.
- If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit.
- If taking edaravone, participant must have initiated edaravone ≥60 days (2 treatment cycles) prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study. Edaravone may not be administered on dosing days of 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.
Key Exclusion Criteria: Part C
- History of or positive test result for human immunodeficiency virus.
- Current hepatitis C infection (defined as positive hepatitis C virus [HCV] antibody and detectable HCV ribonucleic acid [RNA]). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study (United States Centers for Disease Control and Prevention).
- Current hepatitis B infection (defined as positive for HBsAg and/or anti-HBc). participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.
- Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed.
- Current enrollment in any other interventional study.
- 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.
- Current or anticipated need, in the opinion of the Investigator, of a DPS during the study period.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Barrow Neurological Institute
Phoenix, Arizona
85013
United States
University of California San Diego Medical Center
La Jolla, California
92093-0949
United States
California Pacific Medical Center
San Francisco, California
94115
United States
Mayo Clinic in Florida
Jacksonville, Florida
32224
United States
University of Miami School of Medicine
Miami, Florida
33136
United States
Bioclinica Research
Orlando, Florida
32806
United States
Emory University Hospital
Atlanta, Georgia
30322
United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois
60611
United States
Johns Hopkins University
Baltimore, Maryland
21287
United States
Massachusetts General Hospital
Boston, Massachusetts
02114
United States
Henry Ford Hospital
Detroit, Michigan
48202
United States
Mayo Clinic - Rochester
Rochester, Minnesota
55905
United States
Washington University School of Medicine
Saint Louis, Missouri
63110
United States
Neurology Associates, P.C.
Lincoln, Nebraska
68506
United States
Columbia University Medical Center
New York, New York
10032
United States
The Cleveland Clinic Foundation
Cleveland, Ohio
44106
United States
Providence ALS Center
Portland, Oregon
97213
United States
University of Pennsylvania
Philadelphia, Pennsylvania
19104
United States
New Orleans Center for Clinical Research/Volunteer Research Group, an AMR Company
Knoxville, Tennessee
37920
United States
Methodist Neurological Institute
Houston, Texas
77030
United States
Westmead Hospital
Westmead, New South Wales
2145
Australia
UZ Leuven
Leuven 3000
Belgium
University of Calgary - Health Sciences Centre
Calgary, Alberta
T2N 1N4
Canada
Research Site
Edmonton, Alberta
T6G 2G3
Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario
M4N 3M5
Canada
Montreal Neurological Institute
Montreal, Quebec
H3A 2B4
Canada
Bispebjerg Hospital
Copenhagen 2400
Denmark
Hopital Pitie Salpetriere
Paris 75651
France
University of Ulm
Ulm, Baden Wuerttemberg
89081
Germany
ALS Center - Dept. of Neuroscience "Rita Levi Montalcini", University of Turin
Torino 10126
Italy
The University of Tokyo Hospital
Bunkyo-Ku
Japan
Research Site
Fukuoka-shi
Japan
Research Site
Kagoshima City
Japan
Research Site
Shinjuku-ku
Japan
Research Site
Suita-Shi
Japan
Research Site
Yangsan-si, Gyeongsangnam-do
50612
Korea, Republic of
Research Site
Seoul 04763
Korea, Republic of
Research Site
Warszawa 01684
Poland
Research Site
London, Greater London
SE5 9RS
United Kingdom
Research Site
Sheffield, South Yorkshire
S10 2HQ
United Kingdom