Biogen ATLAS Trial (A Study of BIIB067 When Initiated in Clinically Pre-symptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation)

Nov 19, 2021

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Study Title

Biogen ATLAS Trial (A Study of BIIB067 When Initiated in Clinically Pre-symptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation)

Enrollment Status

Recruiting

Principal Investigators

Global Academic Lead: Michael Benatar, MD, PhD.Site-PIs: Michael Benatar, MD, PhD and Volkan Granit, MD

Study Type

Drug Trial

Goals

  • Evaluate whether pre-symptomatic initiation of tofersen can delay the emergence of clinically manifest ALS and/or slow decline in function after emergence of clinically manifest ALS.

Enrolling

Pre-symptomatic SOD1 mutation carriers

Eligibility

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Part A (Natural History Run-In)

  • Age 18+
  • Carrier of a protocol-defined SOD1 mutation
  • Clinically pre-symptomatic for ALS
  • Plasma neurofilament light (NfL) level below protocol-defined threshold at time of screening

Study Involvement

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Part A (Natural History Run-In):

  • Screening 1 (remote): Genetic counseling (pre-test and post-test). Blood draw for DNA, plasma neurofilament light (NfL), and hematology/coagulation testing to determine eligibility.
  • Screening 2 & baseline (in-person): CSF collection.
  • Follow-ups (remote): Monthly blood draw to monitor plasma NfL level, digital assessments, and documention of reported symptoms (if any).

Part B (Randomized Placebo-Controlled):

  • In-person visits to study center
  • Vitals, ECG, blood work, questionnaires
  • Neurological exam (incl. EMG)
  • Lumbar puncture and drug dosing: First 3 doses, every 2 weeks. Thereafter, monthly, until symptoms of clinically manifest ALS develop.

Part C (Open Label Extension):

  • Same visit structure and schedule as Part B.
  • Total length of Parts B + C: 2 years.

Contact

sod1@med.miami.edu

Links

https://clinicaltrials.gov/ct2/show/NCT04856982 https://www.aan.com/MSA/Public/Events/Details/13649

Primary Funding Source

Biogen

Related Publications

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Benatar M, Turner MR, Wuu J. Pre-symptomatic amyotrophic lateral sclerosis: from characterization to prevention. Curr Opin Neurol, 2023 Jun 1. Online ahead of print.

https://pubmed.ncbi.nlm.nih.gov/37382103

Benatar M, Al-Chalabi A, Crawley A, Wuu J. Reply: A new diagnostic entity must enable earlier treatment in gene carriers. Brain. 2023 May 15:awad165. Online ahead of print

https://pubmed.ncbi.nlm.nih.gov/37186590

Benatar M, Wuu J, Andersen PM, Bucelli RC, Andrews JA, Otto M, Farahany NA, Harrington EA, Chen W, Mitchell AA, Ferguson T, Chew S, Gedney L, Oakley S, Heo J, Chary S, Fanning L, Graham D, Sun P, Liu Y, Wong J, Fradette S. Design of a randomized, placebo-controlled, phase 3 trial of tofersen initiated in clinically presymptomatic SOD1 variant carriers: the ATLAS Study. Neurotherapeutics. 2022 May 18. Online ahead of print.

https://pubmed.ncbi.nlm.nih.gov/35585374

Benatar M, Wuu J, McHutchison C, Postuma RB, Boeve BF, Petersen R, Ross CA, Rosen H, Arias JJ, Fradette S, McDermott MP, Shefner J, Stanislaw C, Abrahams S, Cosentino S, Andersen PM, Finkel RS, Granit V, Grignon AL, Rohrer JD, McMillan CT, Grossman M, Al-Chalabi A, Turner MR; attendees of the First International Pre-Symptomatic ALS Workshop. Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases. Brain. 2021 Oct 22. Online ahead of print.

https://pubmed.ncbi.nlm.nih.gov/34677606

Benatar M, Wuu J, Lombardi V, Jeromin A, Bowser R, Andersen PM, Malaspina A. Neurofilaments in pre-symptomatic ALS and the impact of genotype. Amyotroph Lateral Scler Frontotemporal Degener. 2019 Nov;20(7-8):538-548. Epub 2019 Aug 21.

https://pubmed.ncbi.nlm.nih.gov/31432691

Benatar M, Wuu J, Andersen PM, Lombardi V, Malaspina A. Neurofilament light: A candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion. Ann Neurol. 2018 Jul;84(1):130-139. Epub 2018 Aug 16.

https://pubmed.ncbi.nlm.nih.gov/30014505

Benatar M, Stanislaw C, Reyes E, Hussain S, Cooley A, Fernandez MC, Dauphin DD, Michon SC, Andersen PM, Wuu J. Presymptomatic ALS genetic counseling and testing: Experience and recommendations. Neurology. 2016 Jun 14;86(24):2295-302. Epub 2016 May 18.

https://pubmed.ncbi.nlm.nih.gov/27194384

Benatar M, Wuu J. Presymptomatic studies in ALS: rationale, challenges, and approach. Neurology. 2012 Oct 16;79(16):1732-9.

https://pubmed.ncbi.nlm.nih.gov/23071166

Fanos JH, Gronka S, Wuu J, Stanislaw C, Andersen PM, Benatar M. Impact of presymptomatic genetic testing for familial amyotrophic lateral sclerosis. Genet Med. 2011 Apr;13(4):342-8.

https://pubmed.ncbi.nlm.nih.gov/21285887

Related Presentations & Lectures

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Benatar M (presenter), Wuu J, Lombardi V, Andersen PM, Malaspina A. Blood and CSF neurofilament levels as biomarkers of pre-symptomatic disease. Platform presentation at the 28th International Symposium on ALS/MND, Boston, MA, Dec 8-10, 2017.

Benatar M (presenter), Stanislaw C, Reye E, Hussain S, Andersen PM, Wuu J. Pre-Symptomatic ALS genetic counseling and testing: Experience and recommendations. Platform presentation at the 26th International Symposium on ALS/MND, Orlando, FL, Dec 11-13, 2015.

Benatar M (invited speaker). The challenge of early therapeutic intervention in ALS. Invited presentation at the 25th International ALS/MND Meeting. Brussels, Belgium, December 2014.

Gronka S, Walker M, Wuu J, Stanislaw C, Fanos J, Atassi N, Jaffa M, Andersen P, Cudkowicz M, Benatar M (presenter). Telemedicine to facilitate ALS research. Platform presentation at the 21st International Symposium on ALS/MND, Orlando, FL, Dec 11-13, 2010.

Benatar M (speaker). The ATLAS Study: Rationale and design of a phase 3, randomized, placebo-controlled trial of tofersen initiated in clinically presymptomatic SOD1 mutation carriers. NEALS Annual Meeting, Nov 1-3, 2022.

Benatar M (speaker). The ATLAS Study: Rationale and design of a phase 3, randomized, placebo-controlled trial of tofersen initiated in clinically presymptomatic SOD1 mutation carriers. ALS One 5th Annual ALS Research Symposium. Virtual, Oct 6-7, 2022.

Benatar M (keynote speaker). Rethinking ALS: Prodrome, Biomarkers, Disease Prevention. The 1st Ontario Clinical ALS Day (OCAD). Toronto, Canada, Oct 21, 2022.

Benatar M (keynote speaker). Rethinking ALS: Prodrome, Biomarkers, Disease Prevention. Expert-in-the-Field speaker at the 10th Annual University of California Irvine Health Neuromuscular Colloquium. Irvine, CA, June, 2022.

Benatar M (invited speaker). Rethinking ALS: Prodrome, Biomarkers, Disease Prevention. University College London Queen Square Motor Neuron Disease Center Seminar. London, UK, May 2022.

Benatar M (invited speaker). The ATLAS Study. NEALS Webinar (virtual), Mar 17, 2022.

Benatar M (invited speaker). The ATLAS Study. MDA Industry Update Webinar. Virtual, Feb 24, 2022.

Benatar M (invited speaker). Rethinking ALS: Prodrome, Biomarkers, Disease Prevention. Neuroscience Grand Rounds. University of British Columbia, Vancouver, Canada, Feb 2022.

Benatar M (presenter), Wuu J, Andersen PM, Andrews J, Bucelli RC, Otto M, Ferguson TA, Chen W, Fanning L, Graham D, Sun P, Liu Y, Wong J, Fradette S. Design of a phase 3, randomized, placebo-controlled trial of tofersen initiated in clinically presymptomatic SOD1 mutation carriers: The ATLAS Study. Oral presentation at the American Academy of Neurology Virtual Annual Meeting, Apr 17-22, 2021.

Flinders University Center for Neuroscience Seminar. Adelaide, Australia, September 2015.

Benatar M (invited speaker). Challenges and Opportunities in ALS Therapy Development. Congress on Motor and Cognitive Degenerative Diseases. Yachay, Ecuador, January 2015.

Benatar M (invited speaker). ALS Therapy Development: Challenges and Opportunities. ALS Association Wisconsin Chapter. Milwaukee, WI, May 2014.

Benatar M (invited speaker). Predictive, Preventive and Therapeutic Studies in Familial ALS. ALS Association Annual Leadership Forum. Orange County, CA, January 2008.

Benatar M (invited speaker). Strategies for pre-symptomatic biomarker identification in familial ALS. Cold Spring Harbor Symposium on Drug Discovery, Biomarkers, and Clinical Trials for ALS. Banbury Center, Cold Spring Harbor, NY, September 2007.