Study Purpose:
The primary objective of this study is to evaluate the efficacy of tofersen in presymptomatic adult carriers of a superoxide dismutase 1 (SOD1) mutation with elevated neurofilament (NF). The secondary objectives of this study are to evaluate the safety and tolerability tofersen and to evaluate the effect of tofersen on pharmacodynamics (PD)/treatment response biomarkers when initiated prior to versus at the time of emergence of clinically manifest amyotrophic lateral sclerosis (ALS).Study Status:
Recruiting
Disease:
Amyotrophic Lateral Sclerosis Associated With a SOD1 Gene Mutation
Study Type:
Interventional
Type of Intervention:
Drug
Intervention Name:
Tofersen, 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
US Biogen Clinical Trial Center / email hidden; JavaScript is required / 866-633-4636
United States
Study Sponsor:
Biogen
Estimated Enrollment:
150
Estimated Study Start Date:
05 / 17 / 2021
Estimated Study Completion Date:
08 / 07 / 2027
Posting Last Modified Date:
05 / 01 / 2023
Date Study Added to neals.org:
04 / 23 / 2021
Study website/pre-prescreening questionnaire: alsATLASstudy.com
An investigational treatment associated with this study has been approved for sale to the public. More information (https://clinicaltrials.gov/ct2/show/NCT04972487).
Minimum Age:
18 Years
Maximum Age:
N/A
Can participants use Riluzole?
Yes
Key Part A Inclusion Criteria:- Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is approved for inclusion by an external mutation adjudication committee.
- Participants with plasma NfL level less than the protocol-defined threshold.
- Participants who are clinically presymptomatic for ALS (i.e., must not have clinically manifest ALS).
Key Part A Exclusion Criteria:
- History or positive test result at screening for human immunodeficiency virus (HIV). The requirement for testing at Screening may be omitted if it is not permitted by local regulations.
- Current hepatitis C infection (defined as positive Hepatitis C Virus (HCV) antibody and detectable HCV RNA). Participants with positive HCV antibody and undetectable HCV Ribonucleic Acid (RNA) are eligible to participate in the study (United States Centers for Disease Control and Prevention).
- Current hepatitis B infection (defined as positive for hepatitis B surface antigen (HBsAg) and/or anti-Hepatitis B Core antibody (HBc)). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-hepatitis B surface antibody (HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti- HBs) are eligible to participate in the study.
- History of systemic hypersensitivity reaction to tofersen, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study.
- History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in NF, in the opinion of the Investigator.
- Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that if not managed optimally could place a participant at an increased risk for intraoperative or postoperative bleeding.
- Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression
≤ 90 days of screening, which in the opinion of the Investigator would interfere with the study procedures.
- Treatment with riluzole, edaravone, and/or sodium phenylbutyrate/taurursodiol (also known as ursodoxicoltaurine). If the participant has been on riluzole, edaravone, and/or sodium phenylbutyrate/taurursodiol, the medication(s) must be discontinued for at least 5 half-lives prior to Screening.
- Use of off-label treatments for ALS.
- 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.
- Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication (e.g., clopidogrel) that cannot be safely continued or held for an LP procedure, if necessary, according to local or institutional guidelines and/or Investigator determination.
- Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment, biological agent, device, or approved therapy for investigational use. Participation in a noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator.
NOTE: Other protocol defined Inclusion/Exclusion criteria will apply.
Research Site | Recruiting
Rebecca Otutoa / 480-587-6603 / email hidden; JavaScript is required
Scottsdale, Arizona
85251
United States
UC San Diego | Recruiting
Rose Previte / email hidden; JavaScript is required
Principal Investigator : John Ravits
La Jolla, California
92037
United States
California Pacific Medical Center | Recruiting
Ryan Razavi / 415-600-0486 / email hidden; JavaScript is required
Principal Investigator : Jonathan Katz
San Francisco, California
94109
United States
Holy Cross Hospital Phil Smith Neuroscience Institute | Recruiting
Ashley Stepler / 954-542-3442
Principal Investigator : Alameda
Fort Lauderdale, Florida
33308
United States
University of Miami | Recruiting
Anne-Laure Grignon / email hidden; JavaScript is required
Principal Investigator : Michael Benatar
Miami, Florida
33136
United States
Emory University | Recruiting
Meraida Polak / 404-778-3807 / email hidden; JavaScript is required
Principal Investigator : Jonathan Glass
Atlanta, Georgia
30322
United States
Northwestern University | Recruiting
Emma Schmidt / email hidden; JavaScript is required
Chicago, Illinois
60611
United States
Johns Hopkins Hospital | Recruiting
Kristen Riley
Baltimore, Maryland
21287
United States
Massachusetts General Hospital | Recruiting
Kathleen Diana / 617-724-6346 / email hidden; JavaScript is required
Kathleen Diana / 6177246346 / email hidden; JavaScript is required
Principal Investigator : Berry
Boston, Massachusetts
02114
United States
Washington University School of Medicine | Recruiting
Dr Robert Bucelli / 844-257-2273 / email hidden; JavaScript is required
Principal Investigator : Dr Robert Bucelli
Saint Louis, Missouri
63110
United States
Columbia University Medical Center | Recruiting
/ email hidden; JavaScript is required
Principal Investigator : Andrews
New York, New York
10032
United States
Austin Neuromuscular Center | Recruiting
Yessar Hussain / email hidden; JavaScript is required
Stephanie Gonsoulin / email hidden; JavaScript is required
Principal Investigator : Dr. Yessar Hussain
Austin, Texas
78756
United States
Macquarie University | Recruiting
Richard Gan / +61298123739 / email hidden; JavaScript is required
Principal Investigator : Dominic Rowe
Sydney, New South Wales
2109
Australia
UZ Leuven | Recruiting
Prof. Van Damme / email hidden; JavaScript is required
Ann D'Hondt / 0032 16347577 / email hidden; JavaScript is required
Leuven 3000
Belgium
Research Site | Recruiting
São Paulo 04037-002
Brazil
University of Calgary | Recruiting
Berchman Wong / 403-210-7009 / email hidden; JavaScript is required
Principal Investigator : Theodore Mobach, Dr
Calgary, Alberta
T2N 4Z6
Canada
Research Site | Recruiting
Jahan Mookshah / (416) 480-6100 x 87561
Toronto, Ontario
M4N 3M5
Canada
Genge Partners Inc. | Recruiting
Dr. Angela Genge / +1 514 906-3876 Ext. 6026 / email hidden; JavaScript is required
Montréal, Quebec
H3A 2B4
Canada
Hôpital Pitié-Salpêtrière | Recruiting
Gaelle Bruneteau / email hidden; JavaScript is required
Paris 75013
France
Research Site | Recruiting
Ulm 89081
Germany
Hannover Medical School | Recruiting
Prof. Susanne Petri / 00495115323740 / email hidden; JavaScript is required
Hannover 30625
Germany
Cresla "Rita Levi Montalcini" Department of Neuroscience | Recruiting
Christina Moglia / +390116335439 / email hidden; JavaScript is required
Principal Investigator : Adriano Chio
Torino 10126
Italy
Kagoshima University Hospital | Recruiting
Kagoshima-shi, Kagoshima-Ken
890-8520
Japan
University of Tokyo Hospital | Recruiting
Bunkyo-ku, Tokyo-To
113-8655
Japan
Hanyang University Seoul Hospital | Recruiting
Seung Hyun Kim / email hidden; JavaScript is required
Bugyeong Son / 82 2 22909367 / email hidden; JavaScript is required
Seoul 4763
Korea, Republic of
Centrum Medyczne Neuro Protect | Recruiting
Maciej Czarnecki / +48 501762789 / email hidden; JavaScript is required
Warszawa 01-684
Poland
Research Site | Recruiting
Valencia 46026
Spain
University Hospital of Umea | Recruiting
Peter Andersen / email hidden; JavaScript is required
Umeå 90185
Sweden
Sheffield | Recruiting
/ email hidden; JavaScript is required
Principal Investigator : CJ McDermott
Sheffield, Staffordshire
S10 2HQ
United Kingdom