Design of A Phase 3B Trial of Debamestrocel in ALS

Topic:

Clinical Trials

Poster Number: M201

Author(s):

Merit Cudkowicz, MD, MSC, Massachusetts General Hospital, Bob Dagher, MD, Brainstorm Cell Therapeutics, Nathan Staff, MD, Mayo Clinic College of Medicine, Jeremy Shefner, MD, Barrow Neurological Institute, Jinsy Andrews, MD, Columbia University, Jonathan Katz, MD, California Pacific Medical Center, James Berry, MD, Massachusetts General Hospital, Margaret Owegi, MD, University of Massachusetts Medical School, Catherine Douthwright, MD, University of Massachusetts Medical School, Jenny Li, PhD, Massachusetts General Hospital, Melanie Quintana, PhD, Berry Consultants, Yossef Levy, PhD, Massachusetts General Hospital, Chaim Lebovits, Massachusetts General Hospital, Robert Brown, MD, University of Massachusetts Medical School, Tony Windebank, MD, Mayo Clinic College of Medicine, Stacy Lindborg, PhD, Brainstorm Cell Therapeutics

Background: Neurotrophic factor (NTF)-secreting mesenchymal stem cells (MSC-NTF) are a novel cell-therapeutic approach aimed at effectively delivering NTFs directly to the site of damage in ALS patients. MSC-NTF (debamestrocel or NurOwn©) is an autologous, bone marrow-derived, cell therapy currently in phase 3 targeting ALS.

Objective: Present an outline of the phase 3b clinical trial of NurOwn in mild-to-moderate ALS.

Target Enrollment: Approximately 200 patients in the United States

Study Design: This is a two-part, multicenter, Phase 3b study to assess the efficacy and safety of NurOwn in participants with mild-to-moderate ALS. Following screening, eligible patients will undergo bone marrow aspiration and enter a 24-week randomized, double-blind, placebo-controlled period (Part A), followed by a 24-week open-label extension period (Part B). Participants will be randomized 1:1 to the NurOwn and placebo groups. All participants can receive standard-of-care treatment. NurOwn or placebo will be administered by intrathecal injection every eight weeks.

An independent Data Monitoring Committee (DMC) will monitor the safety of the participants.

The key inclusion criteria include participants 18-75 years old, with a diagnosis of ALS per the revised El Escorial criteria, and onset of ALS disease symptoms within 24 months. Participants have evidence of early disease with ≥2 points on each item of the ALSFRS-R, and upright SVC measure ≥65% of predicted for gender, height, and age at Screening. Participants who are receiving standard of care (e.g., riluzole, edaravone, sodium phenylbutyrate/taurursodiol) must be on a stable dose for at least 60 days before Screening.

Outcome Measures: Participants will undergo several safety assessments and efficacy measures including the ALSFRS-R, CAFS, rate of survival, respiratory function (SVC), muscle strength (HHD), patient-reported outcomes such as ALSAQ-40, caregiver burden interview, as well as biomarkers and genetic testing.