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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:

01/17/2020

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
    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
    .(JavaScript must be enabled to view this email address) / 617-643-2522
    Boston, Massachusetts 02114
    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
    Cleveland, Ohio 44106
    United States

    Providence ALS Center
    Portland, Oregon 97213
    United States

    New Orleans Center for Clinical Research
    Knoxville, Tennessee 37920
    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