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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: AT-1501


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ALS diagnosed as possible, laboratory supported probable, probable, or definite as defined by revised El Escorial criteria ALS Functional Rating Scale - Revised (ALSFRS-R) Aggregate score of 37 or greater No more than 24 months from diagnosis Exclusion Criteria: Any other central or peripheral nervous system disease that may interfere with the evaluation of ALS or its progression Presence of a tracheostomy, or use of permanent assistive ventilation (ventilatory support for 23 hours per day or more) History of malignancy within the previous 5 years, except for localized non-melanoma skin cancers 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. Recipient of Stem Cell or Gene Therapy Positive test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV. History of deep venous thrombosis or pulmonary embolism History of active substance abuse within the past 2 years History of stroke, poorly controlled or significant cardiovascular disease, diabetes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, Lou Gehrig's Disease, motor neuron disease, motor neuron degeneration, AT-1501, humanized blocking antibody to CD40LG, CD40L inhibitor, monoclonal antibody