Clinical trial NCT03280056: Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
Official title: A Phase 3, Randomized Double-Blind, Placebo-Controlled Multicenter Study to Evaluate Efficacy and Safety of Repeated Administration of NurOwn® (Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors) in Participants With ALS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Keywords: MSC
Autologous
Neurotrophic factors
Lead sponsor: Brainstorm-Cell Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: California Institute for Regenerative Medicine (CIRM)
First posted: 2017-09-12
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled Multicenter Study
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and efficacy of repeated administration of NurOwn® (MSC-NTF cells) therapy, which is based on transplantation of autologous bone marrow derived mesenchymal stromal cells (MSC), which are enriched from the patient's own bone marrow, propagated ex vivo and induced to secrete Neurotrophic factors (NTFs).

The autologous NurOwn® (MSC-NTF cells) are back-transplanted into the patient intrathecally by standard lumbar puncture where neurons and glial cells are expected to take up the neurotrophic factors secreted by the transplanted cells

Detailed description: Neurotrophic factors (NTFs) are potent survival factors for embryonic, neonatal, and adult neurons and are considered potential therapeutic candidates for ALS. Delivery of multiple NTFs to the immediate environment of afflicted neurons in ALS patients is expected to improve their survival and thus slow down disease progression and alleviate symptoms. NTF-secreting mesenchymal stromal cells (MSC-NTF cells) are a novel cell-therapeutic approach aimed at effectively delivering NTFs directly to the site of damage in ALS patients.

Participants meeting the inclusion and exclusion criteria will be randomized and will undergo bone-marrow aspiration. MSC of the participants randomized to the treatment group will be induced into MSC-NTF cells. Participants will undergo a total of three intrathecal (IT) transplantations with NurOwn® (MSC-NTF cells) or matching placebo at three bi-monthly intervals

Eligibility criteria: Inclusion Criteria:

* ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
* Having onset of ALS disease symptoms, including limb weakness within 24 months at the Screening Visit.
* ALSFRS-R ≥ 25 at the screening Visit.
* Upright slow vital capacity (SVC) measure ≥ 65% of predicted for gender, height, and age at the screening Visit.
* Rapid progressors
* Participants taking a stable dose of Riluzole are permitted in the study
* Citizen or permanent resident of the United States or Canadian citizen able to travel to a US site for all follow-up study visits

Exclusion Criteria:

* Prior stem cell therapy of any kind
* History of autoimmune or other serious disease (including malignancy and immune deficiency) that may confound study results
* Current use of immunosuppressant medication or anticoagulants (per Investigator discretion)
* Exposure to any other experimental agent or participation in an ALS clinical trial within 30 days prior to Screening Visit
* Use of RADICAVA (edaravone injection) within 30 days of screening or intent to use edaravone at any time during the course of the study including the follow up period
* Use of non-invasive ventilation (BIPAP), diaphragm pacing system or invasive ventilation (tracheostomy)
* Feeding tube
* Pregnant women or women currently breastfeeding

Primary outcomes:
measure: The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo
timeFrame: 28 weeks following the first intrathecal injection
Secondary outcomes:
measure: Number of Participants Whose Disease Progression is Halted or Improved as Measured by a 100% or Greater Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score of NurOwn® Treatment vs. Placebo
timeFrame: 28 weeks following the first intrathecal injection
measure: Score of NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by Change From Baseline in ALSFRS-R Score at Week 28
timeFrame: 28 weeks following the first intrathecal injection
measure: NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by the Combined Assessment of Function and Survival at 28 Weeks
timeFrame: 28 weeks following the first intrathecal injection
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine Alpha Stem Cell Clinic
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Boston
country: United States
facility: 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
Study officials:
affiliation: Massachusetts General Hospital
name: Merit E. Cudkowicz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMass Medical School
name: Robert H. Brown, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Anthony J. Windebank, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UC Irvine
name: Namita A. Goyal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: California Pacific Medical Center (CPM) Research Institute
name: Robert G. Miller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedars-Sinai Medical Center
name: Robert Baloh, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: