Clinical trial NCT06973629: Efficacy and Safety of MSC-NTF (NurOwn) in Participants With Early Symptomatic ALS and Moderate Disease Presentation in ALS (ENDURANCE STUDY)
Official title: A Two-Part Phase 3b Randomized, Double-Blind, Placebo-Controlled, Followed by Open-Label Extension, Multicenter Study of the Efficacy and Safety of MSC-NTF (NurOwn) in Participants With With Early Symptomatic and Moderate Disease Presentation in Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis
Keywords: NurOwn
ENDURANCE
Debamestrocel
Lead sponsor: Brainstorm-Cell Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-05-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this two-part clinical trial is:

1) to evaluate the safety and efficacy of Debamestrocel - MSC-NTF (NurOwn) compared to placebo in participants with early symptomatic ALS and moderate disease presentation in ALS; followed by 2) further evaluation by providing NurOwn to all participants in an open label extension period.

Researchers will compare NurOwn to a placebo (a look-alike substance that contains no drug) to evaluate the efficacy of NurOwn compared to placebo in the treatment of participants with ALS.

Participants will:

Receive NurOwn or a placebo every 8 weeks for 24 weeks. After that, every participant will receive NurOwn every 8 weeks for an additional 24 weeks.

They will visit the clinic approximately every 8 weeks for checkups and tests.

Detailed description: This is a multicenter, Phase 3b study to assess the efficacy and safety of NurOwn in participants with early symptomatic ALS and moderate disease presentation in ALS. The study comprises two parts: a 24-week randomized, double blind placebo controlled period (Part A) followed by a 24-week open label expansion period (Part B).

Up to approximately 200 participants are planned to be enrolled and randomized 1:1 to the NurOwn and placebo groups in Part A. All eligible participants who complete Part A will have the option of entering Part B.

The trial includes a 9-week screening period. After the first screening visit (Screening Visit 1), there will be a Screening Visit 2, during which randomization 1:1 to the NurOwn and placebo groups will occur after confirming that all entry criteria are met. Following randomization, bone marrow aspiration will be scheduled. Stem cells from the bone marrow of all participants will be isolated, and then cryopreserved. Prior to each intrathecal (IT) dose administration, cells will be thawed, propagated, and induced into MSC-NTF cells (NurOwn).

In Part A, participants will receive NurOwn or placebo via IT injection every eight weeks at Weeks 0, 8, and 16.

In Part B, participants will receive NurOwn via IT injection every eight weeks at Weeks 24, 32, and 40.

All participants will be offered the option to participate in the collection and storage of blood/serum, CSF, and buccal samples for future analysis of biomarkers and genetic testing.

Eligibility criteria: Inclusion Criteria:

1. Male and female participants 18 to 75 years old (inclusive) at Screening Visit 1.
2. ALS diagnosed as laboratory-supported probable, clinically probable, or definite as defined by the revised El Escorial criteria.
3. Having onset of ALS symptoms, including muscle weakness, within 24 months from Screening Visit 1.
4. ≥2 points on each item of the ALSFRS-R at the Screening Visit 1.
5. ≤45 points on ALSFRS-R total score at Screening Visit 1.
6. Upright slow vital capacity (SVC) measure ≥65% of predicted for gender, height, and age at Screening Visit 1.
7. Participants must adhere to highly effective methods of contraception as specified in the study protocol.

Exclusion Criteria:

1. Prior stem cell therapy of any kind.
2. Active participation in any other ALS interventional study.
3. Inability to lie flat for the duration of IT cell treatment and/or bone marrow biopsy, or inability to tolerate study procedures for any other reason.
4. Any unstable clinically significant medical condition other than ALS
5. Any history of malignancy, within the previous 5 years, with the exception of localized skin cancers, cervical cancer in-situ or prostate cancer in-situ (with no evidence of metastasis, significant invasion, or reoccurrence within 3 years of baseline).
6. Primary brain cancer or cancer with CNS involvement is exclusionary.
7. Other types of motor neuron disease such as primary lateral sclerosis, progressive muscular atrophy, and progressive bulbar palsy.
8. Usage of a feeding tube at Screening Visit 1 or Screening Visit 2.
9. Pregnant women or women currently breastfeeding.

Primary outcomes:
measure: Change in the ALSFRS-R total score from baseline to Week 24
timeFrame: From baseline to Week 24
measure: Frequency and severity of adverse events including treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), death, abnormalities in laboratory evaluations, physical examinations, vital signs and electrocardiogram (ECG) assessments
timeFrame: From baseline to Week 48
Secondary outcomes:
measure: Change in SVC (%predicted) from baseline to Week 24
timeFrame: From baseline to Week 24
measure: Change in HHD from baseline to Week 24
timeFrame: From baseline to Week 24
Other outcomes:
measure: Change in NfL from baseline to Week 24
timeFrame: From baseline to Week 24
measure: Change in ALSAQ-40 scores from baseline to Week 24
timeFrame: From baseline to Week 24
measure: Change in Zarit Caregiver Burden Interview scores from baseline to Week 24
timeFrame: From baseline to Week 24
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus School of Medicine
state: Colorado
city: Davie
country: United States
facility: Nova Southeastern University
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: Boston
country: United States
facility: Sean M. Healey & AMG Center For ALS At Massachusetts General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Portland
country: United States
facility: Providence ALS Center
state: Oregon
city: Philadelphia
country: United States
facility: Temple University Of The Commonwealth System of Higher Education
state: Pennsylvania
Study officials:
References: