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

• ClinicalTrials.gov Identifier: NCT04322149
• Recruitment Status: Completed
• First Posted: March 26, 2020
• Results First Posted: June 28, 2023
• Last Update Posted: June 28, 2023
• Sponsor: Anelixis Therapeutics, LLC
• Information provided by (Responsible Party): Eledon Pharmaceuticals ( Anelixis Therapeutics, LLC )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: AT-1501	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Open-Label, Multi-Center Study to Evaluate the Safety and Tolerability of Multiple Doses of AT-1501 in Adults With ALS
• Actual Study Start Date: October 16, 2020
• Actual Primary Completion Date: March 24, 2022
• Actual Study Completion Date: March 24, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety and Tolerability [ Time Frame: Up to 18 Weeks ]
   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).
2. Safety and Tolerability [ Time Frame: Up to 18 Weeks ]
   Incidence of adverse events (AEs) reported as number of TEAEs (Treatment Emergent Adverse Events) having occurred.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Barrows Neurological Institute

Phoenix, Arizona, United States, 85013

United States, California

University of California Irvine

Orange, California, United States, 92868

California Pacific Medical Center

San Francisco, California, United States, 94109

United States, Georgia

Augusta University

Augusta, Georgia, United States, 30912

United States, Indiana

University of Indiana

Indianapolis, Indiana, United States, 46202

United States, Kansas

The University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Maryland

Johns Hopkins University Medical Center

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, New York

Hospital for Special Surgery (HSS)

New York, New York, United States, 10021

United States, Oregon

Providence Brain & Spine Institute

Portland, Oregon, United States, 97213

United States, Texas

Texas Neurology, P.A.

Dallas, Texas, United States, 75206

Houston Methodist Neurological Institute

Houston, Texas, United States, 77030

Canada

Montreal Neurological Institute and Hospital

Montreal, Canada, H3A 2B4

Sponsors and Collaborators

Anelixis Therapeutics, LLC

Investigators

• Study Chair: Jeff Bornstein, MD; Eledon Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Eledon Pharmaceuticals ( Anelixis Therapeutics, LLC ):

Study Protocol  [PDF] March 8, 2021

Statistical Analysis Plan  [PDF] September 30, 2021

More Information

• Responsible Party: Anelixis Therapeutics, LLC
• ClinicalTrials.gov Identifier: NCT04322149
• Other Study ID Numbers: AT-1501-A201
• First Posted: March 26, 2020
• Results First Posted: June 28, 2023
• Last Update Posted: June 28, 2023
• Last Verified: June 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eledon Pharmaceuticals ( Anelixis Therapeutics, LLC ):

ALS; Lou Gehrig's Disease; motor neuron disease; motor neuron degeneration; AT-1501; humanized blocking antibody to CD40LG; CD40L inhibitor; monoclonal antibody

Additional relevant MeSH terms:

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