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A Study of BIIB067 When Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation (ATLAS)

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ClinicalTrials.gov Identifier: NCT04856982
Recruitment Status : Recruiting
First Posted : April 23, 2021
Last Update Posted : July 13, 2021
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief Summary:
The primary objective of this study is to evaluate the efficacy of BIIB067 when initiated in presymptomatic adult carriers of a superoxide dismutase 1 (SOD1) mutation with elevated neurofilament (NF). The secondary objectives of this study are to evaluate the safety and tolerability of BIIB067 and to evaluate the effect of BIIB067 on pharmacodynamics (PD)/treatment response biomarkers.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Associated With a SOD1 Gene Mutation Drug: BIIB067 (Tofersen) Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Placebo-Controlled Trial With a Longitudinal Natural History Run-In and Open-Label Extension to Evaluate BIIB067 Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation
Actual Study Start Date : May 17, 2021
Estimated Primary Completion Date : August 7, 2026
Estimated Study Completion Date : August 7, 2027


Arm Intervention/treatment
No Intervention: Part A: Natural History Run-in
Participants enrolled in Part A will undergo blood draws approximately once every 28 days to assess neurofilament light chain (NfL) levels.
Experimental: Part B: Randomized, Double-Blind, Placebo-Controlled
Participants from Part A who meet the protocol-defined NfL threshold and remain presymptomatic may be eligible to participate in Part B. During Part B, participants will receive BIIB067 100 milligram (mg) or placebo via intrathecal (IT) injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.
Drug: BIIB067 (Tofersen)
Administered as specified in the treatment arm
Other Name: Tofersen

Drug: Placebo
Administered as specified in the treatment arm

Experimental: Part C: Open-Label Extension
Participants from Part B who develop clinically manifested ALS may be eligible to participate in Part C. During Part C, participants who received placebo in Part B will receive BIIB067 100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years. Participants who received BIIB067 during Part B will receive BIIB067 100 mg on Days 1, 29, and every 28 days thereafter for up to 2 years, with a dose of placebo on Day 15 to maintain the study blind.
Drug: BIIB067 (Tofersen)
Administered as specified in the treatment arm
Other Name: Tofersen

Drug: Placebo
Administered as specified in the treatment arm

Experimental: Part D: Randomized, Double-Blind, Placebo-Controlled
Participants from Part A who develop clinically manifested ALS prior to randomization in Part B may be eligible to participate in Part D. During Part D, participants will be randomized to receive BIIB067 100 mg or placebo via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.
Drug: BIIB067 (Tofersen)
Administered as specified in the treatment arm
Other Name: Tofersen

Drug: Placebo
Administered as specified in the treatment arm




Primary Outcome Measures :
  1. Parts B and C: Percentage of Participants with Emergence of Clinically Manifested ALS Within 1 Year of Part B Baseline [ Time Frame: Up to 1 year ]

Secondary Outcome Measures :
  1. Parts B and C: Percentage of Participants with Emergence of Clinically Manifested ALS Within 2 Years of Part B Baseline [ Time Frame: Up to 2 years ]
  2. Parts B and C: Time to Emergence of Clinically Manifested ALS [ Time Frame: Up to 2 years ]
  3. Parts B and C: Change in Revised ALS Functional Rating Scale (ALSFRS-R) Total Score [ Time Frame: Up to 2 years ]
    The ALSFRS-R measures 4 functional domains: respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 to 4, for a total possible score of 48, with higher scores representing better function.

  4. Parts B and C: Change from Baseline in Percent Predicted Slow Vital Capacity (SVC) [ Time Frame: Up to 2 years ]
  5. Parts B and C: Percentage of Participants with Ventilation Assistance-free Survival (VAFS) [ Time Frame: Up to 2 years ]
    VAFS is defined as time to the earliest occurrence of 1 of the following events: Death or permanent ventilation. Permanent ventilation is defined as ≥ 22 hours of mechanical ventilation [invasive or noninvasive] per day for ≥ 21 consecutive days.

  6. Parts B and C: Percentage of Participants with Overall Survival [ Time Frame: Up to 2 years ]
  7. Parts B, C and D: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the Treatment Period [ Time Frame: Up to 2 years ]
  8. Parts B, C and D: Change from Baseline in Plasma NfL Concentrations [ Time Frame: Up to 2 years ]
  9. Parts B, C and D: Change in Total Cerebrospinal Fluid (CSF) SOD1 Concentrations [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Part A Inclusion Criteria:

  • Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is adjudicated for inclusion by an external mutation adjudication committee.
  • Participants with plasma NfL level less than the protocol-defined threshold.
  • Participants who are clinically presymptomatic for ALS (i.e., must not have clinically manifested ALS).

Key Part A Exclusion Criteria:

  • History or positive test result at screening for human immunodeficiency virus (HIV). The requirement for testing at Screening may be omitted if it is not permitted by local regulations.
  • Current hepatitis C infection (defined as positive Hepatitis C Virus (HCV) antibody and detectable HCV RNA). Participants with positive HCV antibody and undetectable HCV Ribonucleic Acid (RNA) are eligible to participate in the study (United States Centers for Disease Control and Prevention).
  • Current hepatitis B infection (defined as positive for hepatitis B surface antigen (HBsAg) and/or anti-Hepatitis B Core antibody (HBc)). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-hepatitis B surface antibody (HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti- HBs) are eligible to participate in the study.
  • History of systemic hypersensitivity reaction to tofersen, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study.
  • History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in NF, in the opinion of the Investigator.
  • Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that if not managed optimally could place a participant at an increased risk for intraoperative or postoperative bleeding.
  • Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression

    ≤ 90 days of Screening, which in the opinion of the Investigator would interfere with the study procedures.

  • Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication (e.g., clopidogrel) that cannot be safely continued or held for an LP procedure, if necessary, according to local or institutional guidelines and/or Investigator determination.
  • 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 or a plan to enroll in any interventional clinical study in which an investigational treatment, biological agent, device, or approved therapy for investigational use. Participation in a noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator.

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04856982


Contacts
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Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com

Locations
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United States, Florida
Holy Cross Hospital Phil Smith Neuroscience Institute Recruiting
Fort Lauderdale, Florida, United States, 33308
Contact: Donovan Mott    954-542-3442    donovan.mott@holy-cross.com   
Principal Investigator: Eduardo Locatelli         
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Anne-Laure Grignon       axg1571@med.miami.edu   
Principal Investigator: Michael Benatar         
United States, Massachusetts
Research Site Recruiting
Boston, Massachusetts, United States, 02114
United States, Texas
Austin Neuromuscular Center Recruiting
Austin, Texas, United States, 78756
Contact: Yessar Hussain       yessar@austinneuromuscle.com   
Contact: Stephanie Gonsoulin       stephanie@austinneuromuscle.com   
Japan
Research Site Recruiting
Kagoshima-shi, Kagoshima-Ken, Japan, 890-8520
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT04856982    
Other Study ID Numbers: 233AS303
2020-004590-51 ( EudraCT Number )
First Posted: April 23, 2021    Key Record Dates
Last Update Posted: July 13, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases