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

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ClinicalTrials.gov Identifier: NCT03626012
Recruitment Status : Recruiting
First Posted : August 10, 2018
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE August 7, 2018
First Posted Date  ICMJE August 10, 2018
Last Update Posted Date March 19, 2019
Actual Study Start Date  ICMJE September 10, 2018
Estimated Primary Completion Date July 11, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2018)
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline through End of Study (Approximately Day 239) ]
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, places participant at immediate risk of death, requires initial or prolonged inpatient hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly, is a medically important event.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03626012 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2018)
  • Serum BIIB078 Concentration [ Time Frame: Baseline and at multiple time points up to Day 176 ]
  • Area Under the Concentration-Time Curve (AUC) from Time 0 to Infinity (AUCinf) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
  • AUC from Time 0 to Time of the Last Measurable Concentration (AUClast) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
  • Maximum Observed Concentration (Cmax) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
  • Time to Reach Cmax (Tmax) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
  • Terminal Elimination Half-Life (t 1/2) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB078 in Adults With C9ORF72-Associated Amyotrophic Lateral Sclerosis
Official Title  ICMJE 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
Brief Summary The primary objective of this study is to evaluate the safety and tolerability of BIIB078 in adults with C9ORF72-ALS. The secondary objective of this study is to evaluate the pharmacokinetic profile of BIIB078.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Drug: BIIB078
    Administered as specified in the treatment arm.
  • Drug: Placebo
    Administered as specified in the treatment arm.
Study Arms  ICMJE
  • Experimental: Cohort 1: BIIB078 First Dosage
    BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.
    Intervention: Drug: BIIB078
  • Experimental: Cohort 2: BIIB078 Second Dosage
    BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.
    Intervention: Drug: BIIB078
  • Experimental: Cohort 3: BIIB078 Third Dosage
    BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.
    Intervention: Drug: BIIB078
  • Experimental: Cohort 4: BIIB078 Fourth Dosage
    BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.
    Intervention: Drug: BIIB078
  • Experimental: Cohort 5: BIIB078 Fifth Dosage
    BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.
    Intervention: Drug: BIIB078
  • Experimental: Cohort 6: BIIB078 Sixth Dosage
    BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.
    Intervention: Drug: BIIB078
  • Placebo Comparator: Cohorts 1-6: Placebo
    Matching placebo will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 15, 2018)
80
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2018)
59
Estimated Study Completion Date  ICMJE July 11, 2022
Estimated Primary Completion Date July 11, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Ability of the subject 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 subject privacy regulations; or, in the event of the subject'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 subjects 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).
  • Subjects 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).
  • Subjects 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 subject as to be able to provide accurate information about the subject's cognitive and functional abilities at Screening.

Key Exclusion Criteria:

  • History of drug abuse or alcoholism ≤ 6 months of Screening that would limit participation in the study, as determined by the Investigator.
  • Tracheostomy.
  • 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 anti-platelet or anticoagulant therapy ≤ 14 days before Screening (with the exception of aspirin ≤ 325 mg/day) or anticipated use during the study.
  • Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
  • Female subjects who are pregnant or currently breastfeeding.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03626012
Other Study ID Numbers  ICMJE 245AS101
2017-000294-36 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP