Efficacy and Safety of MSC-NTF (NurOwn) in Participants With Early Symptomatic ALS and Moderate Disease Presentation in ALS (ENDURANCE STUDY)

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.

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.