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)

Overview

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.

Interventions

• Biological Debamestrocel - MSC-NTF (NurOwn)
  MSC-NTF cells suspended in excipient Dulbecco Modified Eagle Medium (DMEM).
• Biological Placebo
  Dulbecco Modified Eagle Medium (DMEM).

Primary outcome measures

• Change in the ALSFRS-R total score from baseline to Week 24 [Time frame: From baseline to Week 24]
• 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 [Time frame: From baseline to Week 48]

Secondary outcome measures (2)

• Change in SVC (%predicted) from baseline to Week 24 [Time frame: From baseline to Week 24]
• Change in HHD from baseline to Week 24 [Time frame: From baseline to Week 24]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Prior stem cell therapy of any kind.
• Active participation in any other ALS interventional study.
• 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.
• Any unstable clinically significant medical condition other than ALS
• 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).
• Primary brain cancer or cancer with CNS involvement is exclusionary.
• Other types of motor neuron disease such as primary lateral sclerosis, progressive muscular atrophy, and progressive bulbar palsy.
• Usage of a feeding tube at Screening Visit 1 or Screening Visit 2.
• Pregnant women or women currently breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 15 centers

• Barrow Neurological Institute — Phoenix
• University of California San Diego Medical Center — La Jolla
• University of Southern California — Los Angeles
• California Pacific Medical Center — San Francisco
• University of California, San Francisco — San Francisco
• University of Colorado Anschutz Medical Campus School of Medicine — Aurora
• Nova Southeastern University — Davie
• Mayo Clinic — Jacksonville
• … and 7 more centers

Identifiers

NCT: NCT06973629 · BCT-006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗