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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04856982




Registration number
NCT04856982
Ethics application status
Date submitted
20/04/2021
Date registered
23/04/2021

Titles & IDs
Public title
A Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation
Scientific 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
Secondary ID [1] 0 0
2020-004590-51
Secondary ID [2] 0 0
233AS303
Universal Trial Number (UTN)
Trial acronym
ATLAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis Associated With a SOD1 Gene Mutation 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Tofersen
Treatment: Drugs - Placebo

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 tofersen 100 milligram (mg) or placebo via intrathecal (IT) injection on Days 1, 15, 29, and every 28 days thereafter for up to approximately 5.6 years.

Experimental: Part C: Open-Label Extension - Participants from Part B who develop clinically manifest ALS may be eligible to participate in Part C. During Part C, participants who received placebo in Part B will receive tofersen 100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter up to the final maintenance dost visit. Participants who received tofersen during Part B will receive tofersen 100 mg on Days 1, 29, and every 28 days thereafter up to the final maintenance dost visit, with a dose of placebo on Day 15 to maintain the study blind. The combined duration of Part B and Part C is up to approximately 5.6 years.

Experimental: Part D: Open-Label Treatment - Participants from Part A who develop clinically manifest ALS prior to randomization in Part B may be eligible to participate in Part D. During Part D, participants will receive tofersen100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.


Treatment: Drugs: Tofersen
Administered as specified in the treatment arm

Treatment: Drugs: Placebo
Administered as specified in the treatment arm
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parts B and C: Percentage of Participants with Emergence of Clinically Manifest ALS Within 24 Months of Part B Baseline
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Parts B and C: Time to Emergence of Clinically Manifest ALS
Timepoint [1] 0 0
Up to 5.6 years
Secondary outcome [2] 0 0
Parts B and C: Change in ALS Functional Rating Scale (ALSFRS-R) Total Score
Timepoint [2] 0 0
Up to 5.6 years
Secondary outcome [3] 0 0
Parts B and C: Change from Baseline in Percent Predicted Slow Vital Capacity (SVC)
Timepoint [3] 0 0
Up to 5.6 years
Secondary outcome [4] 0 0
Parts B and C: Percentage of Participants with Outcome as Death or Permanent Ventilation Based on Time to Death or Permanent Ventilation Analysis
Timepoint [4] 0 0
Up to 5.6 years
Secondary outcome [5] 0 0
Parts B and C: Percentage of Participants with Outcome as Deaths Based on Time to Death Analysis
Timepoint [5] 0 0
Up to 5.6 years
Secondary outcome [6] 0 0
Parts B, C and D: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the Treatment Period
Timepoint [6] 0 0
Parts B and C: Up to 5.6 years and Part D: Up to 2 years
Secondary outcome [7] 0 0
Parts B, C and D: Change from Baseline in Plasma NfL Concentrations
Timepoint [7] 0 0
Parts B and C: Up to 5.6 years and Part D: Up to 2 years
Secondary outcome [8] 0 0
Parts B, C and D: Change in Total Cerebrospinal Fluid (CSF) SOD1 Concentrations
Timepoint [8] 0 0
Parts B and C: Up to 5.6 years and Part D: Up to 2 years

Eligibility
Key inclusion criteria
Key Part A

* Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is approved 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 manifest ALS).

Key Part A
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.
* Treatment with riluzole, edaravone, and/or sodium phenylbutyrate/taurursodiol (also known as ursodoxicoltaurine). If the participant has been on riluzole, edaravone, and/or sodium phenylbutyrate/taurursodiol, the medication(s) must be discontinued for at least 5 half-lives prior to Screening.
* Use of off-label treatments for ALS.
* 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.
* 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.
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
7/08/2027
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Macquarie University - Sydney
Recruitment postcode(s) [1] 0 0
2109 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Belgium
State/province [11] 0 0
Flemish Brabant
Country [12] 0 0
Brazil
State/province [12] 0 0
Sao Paulo
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
Germany
State/province [17] 0 0
Baden Wuerttemberg
Country [18] 0 0
Germany
State/province [18] 0 0
Niedersachsen
Country [19] 0 0
Italy
State/province [19] 0 0
Torino
Country [20] 0 0
Japan
State/province [20] 0 0
Kagoshima-Ken
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo-To
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Poland
State/province [23] 0 0
Mazowieckie
Country [24] 0 0
Spain
State/province [24] 0 0
Valencia
Country [25] 0 0
Sweden
State/province [25] 0 0
Västerbotten County
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Staffordshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US Biogen Clinical Trial Center
Address 0 0
Country 0 0
Phone 0 0
866-633-4636
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04856982