A Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB067 Administered to Adult Subjects With ALS and Confirmed Superoxide Dismutase 1 Mutation (VALOR)

Study Purpose:

The primary objective of Parts A and B of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of BIIB067 (Tofersen) in adult with ALS. The primary objective of Part C of this study is to evaluate the clinical efficacy of BIIB067 administered to adult participants with ALS and confirmed superoxide dismutase 1 (SOD1) mutation.

The secondary objective of Parts A and B of this study is to evaluate the effects of BIIB067 on levels of SOD1 protein in the cerebrospinal fluid (CSF). The secondary objectives of Part C are to evaluate the safety, tolerability, and pharmacodynamic (PD) effects of BIIB067 administered to adult participants with ALS and confirmed SOD1 mutation.

Disease:

Amyotrophic Lateral Sclerosis (ALS)

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase III

Study Chair(s)/Principal Investigator(s):

Clinicaltrials.gov ID (11 digit #):

NCT02623699

Neals Affiliated?

Yes

Coordinating Center Contact Information

US Biogen Clinical Trial Center / .(JavaScript must be enabled to view this email address) / 866-633-4636
.(JavaScript must be enabled to view this email address) United States

Full Study Summary:

This is a 3-part study to examine the efficacy, safety, tolerability, PK and PD of BIIB067. Part A is the single ascending dose (SAD) component of the study, Part B is the multiple ascending dose (MAD) component of the study and Part C is the fixed dose component of the study. Hence, the overall phase of development of the study is 1/2/3.

Parts A and B were completed on 15-Jan-2019. In total, the study is estimated to enroll 183 participants, with 99 in Part C.

Study Sponsor:

Biogen

Participant Duration:

Estimated Enrollment:

183

Estimated Study Start Date:

01/20/2016

Estimated Study Completion Date:

07/06/2021

Posting Last Modified Date:

02/25/2020

Date Study Added to alsconsortium.org:

05/08/2019

Eligibility Criteria

Gender:
Female, Male
Minimum Age:
18
Maximum Age:
N/A

Time since Symptom Onset:

Time since Diagnosis:

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.
Site Contact Information

Barrow Neurological Institute
Aide Raya / .(JavaScript must be enabled to view this email address) / 602-406-8144
Phoenix, Arizona 85013
United States

University of California San Diego Medical Center
Rose Previte / .(JavaScript must be enabled to view this email address) / 858-246-1319
La Jolla, California 92093
United States

California Pacific Medical Center
Jennifer Milan / .(JavaScript must be enabled to view this email address) / 415-600-5764
San Francisco, California 94115
United States

Bioclinica Research
Matthew Bubalo / .(JavaScript must be enabled to view this email address) / 407-734-7841
Orlando, Florida 32806
United States

University of Miami School of Medicine
Anne-Laure Grignon / .(JavaScript must be enabled to view this email address) / 305-243-8928
Miami, Florida 33136
United States

Mayo Clinic in Florida
Jacksonville , Florida 32224
United States

Emory University Hospital
Atlanta, Georgia 30322
United States

Johns Hopkins University
Kristen Riley / .(JavaScript must be enabled to view this email address) / Baltimore, Maryland 21287
United States

Massachusetts General Hospital
Jenna Doherty / .(JavaScript must be enabled to view this email address) / 617-643-0312
Boston, Massachusetts 02114
United States

Henry Ford Hospital
Anne Vallis / .(JavaScript must be enabled to view this email address) / 313-916-1364
Detroit, Michigan 48202
United States

Mayo Clinic - Rochester
Jane Sultze / .(JavaScript must be enabled to view this email address) / 507-538-5523
Rochester, Minnesota 55905
United States

Washington University School of Medicine
Jesse Markway / .(JavaScript must be enabled to view this email address) / 844-257-2273 or 314-362-6159
Saint Louis, Missouri 63110
United States

Neurology Associates, P.C.
Ashley Calhoun / .(JavaScript must be enabled to view this email address) / 402-770-7403
Lincoln, Nebraska 68506
United States

Columbia University Medical Center
New York, New York 10032
United States

The Cleveland Clinic Foundation
Debbie Hastings / .(JavaScript must be enabled to view this email address) / 216-445-3353
Cleveland, Ohio 44106
United States

Providence ALS Center
Arlena Cummings, CCRP / .(JavaScript must be enabled to view this email address) / 503-962-1171
Portland, Oregon 97213
United States

New Orleans Center for Clinical Research
Knoxville, Tennessee 37920
United States

Methodist Neurological Institute
Sharon Halton / .(JavaScript must be enabled to view this email address) / 713-441-3420
Houston, Texas 77030
United States

Westmead Hospital
Steve Vucic / .(JavaScript must be enabled to view this email address) / +61 2 8890 8738
Westmead, New South Wales
Australia

UZ Leuven
.(JavaScript must be enabled to view this email address) / +32 16344280
Leuven,
Belgium

Sunnybrook Health Sciences Centre
Jahan Mookshah / .(JavaScript must be enabled to view this email address) / 416-480-6100 ext x87561
Toronto , Ontario M4N 3M5
Canada

Montreal Neurological Institute
Yousra Khalfallah / .(JavaScript must be enabled to view this email address) / 514-398-6188
Montreal, Quebec H3A 2B4
Canada

Hospitalier Pitie Salpetriere
Maryvonne Retail / .(JavaScript must be enabled to view this email address) / 01 42 16 19 70
Paris,
France

Universitaetsklinikum Ulm
Sebastian Michels / .(JavaScript must be enabled to view this email address) / +49 (0)731-177 5219
Ulm, Baden Wuerttemberg 89081
Germany

University of Turin
Giuseppe Fuda / .(JavaScript must be enabled to view this email address) / +39 011 6335439
ALS Center - Dept. of Neuroscience "Rita Levi Montalcini"
Torino,
Italy

Research Site
Suita-Shi, Osaka-Fu
Japan

Research Site
Bunkyo-Ku, Tokyo-To
Japan

Research Site
Shinjuku-ku, Tokyo-To
Japan

Research Site
Kagoshima City, Kagoshima-Ken 890-8520
Japan

Sheffield Institute for Translational Neuroscience
Sheffield, South Yorkshire S10 2HQ
United Kingdom