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)

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 will be the fixed dose component of the study. Hence, the overall phase of development of the study is 1/2/3.

• Eligibility Criteria

  Gender:

  Female, Male

  Minimum Age:

  18

  Maximum Age:

  N/A

  Min Vital Capacity (% predicted normal):

  50

  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.
  History of, or positive test result at Screening, for hepatitis C virus antibody.
  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 IgM anti-HBc, and positive anti-HBc) or vaccination (defined as 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.

• Site Contact Information

  Barrow Neurological Institute
  Phoenix, Arizona 85013
  United States

  University of California San Diego Medical Center
  La Jolla, California 92093
  United States

  California Pacific Medical Center
  San Francisco, California 94115
  United States

  Bioclinica Research
  Orlando, Florida 32806
  United States

  University of Miami School of Medicine
  Miami, Florida 33136
  United States

  Emory University Hospital
  Atlanta, Georgia 30322
  United States

  Johns Hopkins University
  Baltimore, Maryland 21287
  United States

  Massachusetts General Hospital
  Boston, Massachusetts 02114
  United States

  Washington University School of Medicine
  Saint Louis, Missouri 63110
  United States

  Neurology Associates, P.C.
  Lincoln, Nebraska 68506
  United States

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

  UZ Leuven
  Leuven, 3000
  Belgium

  Sunnybrook Health Sciences Centre
  Toronto , Ontario M4N 3M5
  Canada

  Montreal Neurological Institute
  Montreal, Quebec H3A 2B4
  Canada

  Hospitalier Pitie-Salpetriere
  Paris, 75651
  France

  Universitaetsklinikum Ulm
  Ulm, Baden Wuerttemberg 89081
  Germany

  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,
  Japan

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