Multiple Doses of AT-1501-A201 in Adults With ALS

A Phase 2a Open-Label, Multi-Center Study to Evaluate the Safety and Tolerability of Multiple Doses of AT-1501 in Adults With ALS

This is a Phase 2a, multi-center, open label, multiple dose study of AT-1501, a humanized monoclonal antibody antagonist to CD40 ligand (CD40L). Approximately 54 adults with Amyotrophic Lateral Sclerosis (ALS) will be enrolled into the study in the United States and Canada at approximately 13 ALS treatment sites.

Participants will be enrolled into one of four ascending doses.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: AT-1501

Detailed Description

This is a Phase 2a, multi-center, open label, multiple dose study of AT-1501, a humanized monoclonal antibody antagonist to CD40L. Approximately 54 adults with ALS will be enrolled into the study in the United States and Canada at approximately 13 ALS treatment sites.

Four ascending doses of AT-1501 will be administered as an IV infusion to sequentially enrolling cohorts. Each participant will receive 6 bi-weekly (every other week) infusions of AT-1501 over an 11-week period.

The study is estimated to take 19 weeks for participants.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Montreal, Canada, H3A 2B4
    • Montreal Neurological Institute and Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrows Neurological Institute
  • California
    • Orange, California, United States, 92868
      • University of California Irvine
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • University of Indiana
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery (HSS)
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Brain & Spine Institute
  • Texas
    • Dallas, Texas, United States, 75206
      • Texas Neurology, P.A.
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ALS diagnosed as possible, laboratory supported probable, probable, or definite as defined by revised El Escorial criteria
2. ALS Functional Rating Scale - Revised (ALSFRS-R) Aggregate score of 37 or greater
3. No more than 24 months from diagnosis

Exclusion Criteria:

1. Any other central or peripheral nervous system disease that may interfere with the evaluation of ALS or its progression
2. Presence of a tracheostomy, or use of permanent assistive ventilation (ventilatory support for 23 hours per day or more)
3. History of malignancy within the previous 5 years, except for localized non-melanoma skin cancers

4. Abnormal function of the immune system resulting from:

   • Clinical conditions affecting the immune system (e.g. HIV infection, agammaglobulinemia),
   • Systemic administration of corticosteroids (PO/IV/IM) at a dose equivalent to 20 mg/day of prednisone for more than 14 consecutive days within 90 days prior to screening,
   • Administration of anti-neoplastic and/or immunomodulating agents (e.g. Tumor necrosis factor alpha (TNF α) antagonists or anti-B cell antibodies) or radiotherapy within 1 year prior to screening.
5. Recipient of Stem Cell or Gene Therapy
6. Positive test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV.
7. History of deep venous thrombosis or pulmonary embolism
8. History of active substance abuse within the past 2 years
9. History of stroke, poorly controlled or significant cardiovascular disease, diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AT-1501; 4 sequential dose cohorts	Drug: AT-1501; AT-1501 monoclonal antibody targeting CD40L given as an IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Incidence of adverse events (AEs) reported as number of participants with at least one TEAE (Treatment Emergent Adverse Event) and at least one SAE (Serious Adverse Event).	Up to 18 Weeks
Safety and Tolerability	Incidence of adverse events (AEs) reported as number of TEAEs (Treatment Emergent Adverse Events) having occurred.	Up to 18 Weeks

Collaborators and Investigators

• Sponsor: Anelixis Therapeutics, LLC
• Investigators: Study Chair: Jeff Bornstein, MD, Eledon Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2020
• Primary Completion (Actual): March 24, 2022
• Study Completion (Actual): March 24, 2022

Study Registration Dates

• First Submitted: March 20, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: ALS; monoclonal antibody; motor neuron disease; Lou Gehrig's Disease; AT-1501; CD40L inhibitor; motor neuron degeneration; humanized blocking antibody to CD40LG
• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: AT-1501-A201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No