A Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB078 in Adults With C9ORF72-Associated Amyotrophic Lateral Sclerosis

Trial ID or NCT#



not recruiting iconNOT RECRUITING


The primary objective of this study is to evaluate the safety and tolerability of BIIB078 in adults with C9ORF72-Amyotrophic Lateral Sclerosis (ALS). The secondary objectives of this study are to evaluate the pharmacokinetic profile of BIIB078 and to evaluate the effects of BIIB078 on clinical function. As the first-in-human study, the study enrolls a small number of participants in each cohort. Every participant in a cohort is treated with the same dose or placebo. The study is designed to evaluate and confirm the safety of each dose before enrolling and exposing new participants to a higher dose in the next cohort.

Official Title

A Phase 1 Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB078 Administered Intrathecally to Adults With C9ORF72-Associated Amyotrophic Lateral Sclerosis

Eligibility Criteria

Ages Eligible for Study: Older than 18 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Inclusion Criteria:
  1. - Ability of the participant to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information in accordance with national and local participant privacy regulations; or, in the event of the participant's physical incapacity to sign, to confirm that understanding and consent orally to a legally authorized representative (LAR) for the express purpose of having said informed consent and authorization signed on his/her behalf. - All participants of childbearing potential must agree to practice highly effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment. - Must meet the possible, laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria and have documentation of a clinical genetic test demonstrating the presence of a pathogenic mutation in C9ORF72. - Slow vital capacity (SVC) ≥ 50% of predicted value as adjusted for sex, age, and height (from the sitting position). - Participants taking concomitant riluzole at study entry must be on a stable dose for ≥ 30 days prior to the first dose of study treatment (Day 1). - Participants taking concomitant edaravone at study entry must be on a stable dose for ≥ 60 days prior to the first dose of study treatment (Day 1). - ALS Cognitive Behavioral Screen (ALS-CBS) score ≥ 11 for the cognitive portion; ≥ 33 for the behavioral portion. - 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. - Screening values of coagulation parameters including platelet count, international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (APTT) should be within normal ranges. - Has an informant/caregiver who, in the Investigator's judgment, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities at Screening. Key
Exclusion Criteria:
  1. - History of drug abuse or alcoholism ≤ 6 months of Screening that would limit participation in the study, as determined by the Investigator. - Tracheostomy. - Prescreening ALSFRS-R slope less than 0.4 points/month, where prescreening ALSFRS-R slope is defined as follows: (48 - ALSFRS-R score at Screening) / (months from date of symptom onset to date of Screening). - History of or positive test result at Screening for human immunodeficiency virus. . - History of, or positive test result at Screening for, hepatitis C virus antibody. - Treatment with another investigational drug or biological agent within 1 month of Screening or 5 half-lives of study agent, whichever is longer. - Treatment with an antiplatelet or anticoagulant therapy that cannot safely be interrupted for lumbar puncture (LP) according to local standard of care and/or institutional guidelines, in the opinion of the Investigator or Prescriber. - Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period. - Female participants who are pregnant or currently breastfeeding. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


John W. Day, MD, PhD
John W. Day, MD, PhD
Neuromuscular neurologist, Neurophysiologist
Professor of Neurology (Adult Neurology), of Pediatrics (Genetics) and, by courtesy, of Pathology