Clinical trial NCT04322149: Multiple Doses of AT-1501-A201 in Adults With ALS
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Lou Gehrig's Disease
motor neuron disease
motor neuron degeneration
AT-1501
humanized blocking antibody to CD40LG
CD40L inhibitor
monoclonal antibody
Lead sponsor: Eledon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-03-26
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Safety and Tolerability
timeFrame: Up to 18 Weeks
measure: Safety and Tolerability
timeFrame: Up to 18 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrows Neurological Institute
state: Arizona
city: Orange
country: United States
facility: University of California Irvine
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Indianapolis
country: United States
facility: University of Indiana
state: Indiana
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Hospital for Special Surgery (HSS)
state: New York
city: Portland
country: United States
facility: Providence Brain & Spine Institute
state: Oregon
city: Dallas
country: United States
facility: Texas Neurology, P.A.
state: Texas
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
Study officials:
affiliation: Eledon Pharmaceuticals
name: Jeff Bornstein, MD
role: STUDY_CHAIR
References: