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

NCT ID: NCT03626012

Last Updated: 2022-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-10
• Study Completion Date: 2021-11-17

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

BIIB078

Intervention Type: DRUG

Administered as specified in the treatment arm.

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.

Group Type: EXPERIMENTAL

BIIB078

Intervention Type: DRUG

Administered as specified in the treatment arm.

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.

Group Type: EXPERIMENTAL

BIIB078

Intervention Type: DRUG

Administered as specified in the treatment arm.

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 five maintenance doses on five later days.

Group Type: EXPERIMENTAL

BIIB078

Intervention Type: DRUG

Administered as specified in the treatment arm.

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 five maintenance doses on five later days.

Group Type: EXPERIMENTAL

BIIB078

Intervention Type: DRUG

Administered as specified in the treatment arm.

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 five maintenance doses on five later days.

Group Type: EXPERIMENTAL

BIIB078

Intervention Type: DRUG

Administered as specified in the treatment arm.

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 (Cohorts 1 through 3) and five maintenance doses on five later days (Cohorts 4 through 6).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Administered as specified in the treatment arm.

Interventions

BIIB078

Administered as specified in the treatment arm.

Intervention Type: DRUG

Placebo

Administered as specified in the treatment arm.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

Research Site

La Jolla, California, United States

Research Site

Los Angeles, California, United States

Research Site

Palo Alto, California, United States

Research Site

Jacksonville, Florida, United States

Research Site

Miami, Florida, United States

Research Site

Atlanta, Georgia, United States

Research Site

Baltimore, Maryland, United States

Research Site

Boston, Massachusetts, United States

Research Site

St Louis, Missouri, United States

Research Site

Lincoln, Nebraska, United States

Research Site

New York, New York, United States

Research Site

Knoxville, Tennessee, United States

Research Site

Calgary, Alberta, Canada

Research Site

Toronto, Ontario, Canada

Research Site

Montreal, Quebec, Canada

Research Site

Dublin, , Ireland

Research Site

Utrecht, , Netherlands

Research Site

Sankt Gallen, , Switzerland

Research Site

London, Greater London, United Kingdom

Research Site

Sheffield, South Yorkshire, United Kingdom

Research Site

London, , United Kingdom

Countries

United States; Canada; Ireland; Netherlands; Switzerland; United Kingdom

References

van den Berg LH, Rothstein JD, Shaw PJ, Babu S, Benatar M, Bucelli RC, Genge A, Glass JD, Hardiman O, Libri V, Mobach T, Oskarsson B, Pattee GL, Ravits J, Shaw CE, Weber M, Zinman L, Jafar-Nejad P, Rigo F, Lin L, Ferguson TA, Gotter AL, Graham D, Monine M, Inra J, Sinks S, Eraly S, Garafalo S, Fradette S. Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study. Lancet Neurol. 2024 Sep;23(9):901-912. doi: 10.1016/S1474-4422(24)00216-3. Epub 2024 Jul 23.

Reference Type: DERIVED

PMID: 39059407 (View on PubMed)

Other Identifiers

2017-000294-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

245AS101

Identifier Type: -

Identifier Source: org_study_id