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NurOwn® (debamestrocel) in amyotrophic lateral sclerosis

A two-part, multicenter Phase 3b study assesses the efficacy and safety of autologous MSC-NTF cells in participants earlier in the course of their disease. The protocol and statistical analysis plan have been granted a Special Protocol Assessment by the FDA - meaning they are adequate to support a future Biologics License Application.

Study BCT-006-US · ENDURANCE

Phase 3b trial in ALS

A two-part, multicenter study assessing the efficacy and safety of NurOwn in participants earlier in the course of their disease. The protocol and statistical analysis plan have been granted a Special Protocol Assessment by the FDA - meaning they are adequate to support a future Biologics License Application.

This study is not yet registered on ClinicalTrials.gov, so no registry identifier is shown.

Design
Two-part, multicenter, randomized
Target enrollment
~200 participants in the United States
Randomization
1:1 NurOwn vs placebo
Entry criteria
Symptom onset within 24 months; SVC ≥ 65% predicted
Administration
Three intrathecal injections, every 8 weeks
Regulatory
FDA Special Protocol Assessment agreement

Trial design

  • Screening

    6–9 weeks

    A single bone-marrow aspiration procures the MSCs used to manufacture each participant’s treatment for the whole trial.

  • Part A

    24 weeks · double-blind

    Placebo-controlled. Up to ~200 patients randomized 1:1 to NurOwn or placebo, three intrathecal injections every eight weeks.

  • Part B

    24 weeks · open-label extension

    All eligible completers may receive three repeated intrathecal injections of NurOwn, once every eight weeks.

  • Primary endpoint

    Change in ALSFRS-R total score from baseline to week 24.

  • Primary inference

    p-value from the combined assessment of function and survival (CAFS).

  • Biomarkers

    CSF and blood sampling for neuroinflammation, neurodegeneration and neuroprotection.

Completed trials in ALS

Four completed trials in ALS

Two open-label trials in Israel and two multicenter, double-blind, placebo-controlled trials in the United States. Across these studies, MSC-NTF cell administration was generally well tolerated; the safety profile reported in each is summarized below.

  • Phase 1/2 · Israel

    Single-arm, single dose, open label

    NCT01051882N = 12

    Administration of autologous MSC-NTF cells was found to be safe and well tolerated during these six-month trials.

  • Phase 2a · Israel

    Single-arm, single ascending dose

    NCT01777646N = 14

    Clinically meaningful improvements in the rate of disease progression were observed for the six months following treatment on both the ALSFRS-R and FVC. Published in JAMA Neurology.

  • Phase 2 · United States

    Randomized, placebo-controlled, double-blind, single dose

    NCT02017912N = 48

    Safe and well tolerated, with the majority of adverse events mild or moderate. A reduction in the rate of progression was observed in the treatment group but not placebo, and was statistically significant in a subpopulation with more rapid progression. CSF biomarkers confirmed NTF secretion and reduced inflammatory activity.

  • Phase 3 · United States

    Randomized, placebo-controlled, double-blind, multi-dose

    NCT03280056N = 189

    Well tolerated with no safety concerns. Participants were screened during an 18-week run-in period and only rapid progressors were randomized. The primary endpoint was not met; however a pre-specified analysis of participants with baseline ALSFRS-R ≥ 35 showed a clinical response at 28 weeks. Significant improvements in CSF biomarkers of neuroinflammation, neurodegeneration and neurotrophic support were observed, with placebo unchanged.

Measuring progression

The ALSFRS-R

The ALS Functional Rating Scale-Revised (ALSFRS-R) is a widely accepted, validated measure of disease progression used in clinical trials. It measures physical function in performing activities of daily living across 12 items and four domains.

The rate of decline in ALSFRS-R score is an important predictor of survival and prognosis. Without treatment, the average rate of decline is about one point per month.

Domain 01

Bulbar function

Speech, Salivation, Swallowing

Domain 02

Fine motor function

Writing, Cutting Food/Using Utensils, Dressing and Hygiene

Domain 03

Gross motor function

Turning in Bed and Adjusting Bedclothes, Walking, Climbing Stairs

Domain 04

Respiratory function

Dyspnea, Orthopnea, Respiratory Support

Source: Cedarbaum JM, et al. J Neurol Sci. 1999;169:13-21.

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BrainStorm's autologous MSC-NTF cell therapy (NurOwn®, debamestrocel) is investigational and has not been approved by the FDA or any other regulatory authority.