Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients

Amyotrophic Lateral Sclerosis (ALS) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03280056
• Other study ID #: BCT-002-US
• Status: Completed
• Phase: Phase 3
• Start date: August 28, 2017
• Est. completion date: September 29, 2020

Study information

• Verified date: February 2024
• Source: Brainstorm-Cell Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: September 29, 2020
• Est. primary completion date: September 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Amyotrophic Lateral Sclerosis (ALS)
• Motor Neuron Disease

Intervention

Biological:
• NurOwn® (MSC-NTF cells)
NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10^6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors

Other:
• Placebo
One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection
• Bone Marrow aspiration
Bone Marrow aspiration

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of California Irvine Alpha Stem Cell Clinic	Irvine	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Mayo Clinic	Rochester	Minnesota
United States	California Pacific Medical Center	San Francisco	California
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brainstorm-Cell Therapeutics	California Institute for Regenerative Medicine (CIRM)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.	28 weeks following the first intrathecal injection
Secondary	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	The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.	28 weeks following the first intrathecal injection
Secondary	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	The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.	28 weeks following the first intrathecal injection
Secondary	NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by the Combined Assessment of Function and Survival at 28 Weeks	The combined Assessment of Function and Survival (CAFS) is a composite endpoint based on (1) the change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) score and (2) time to death.; On the ALSFRS-R, 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a total score range (minimum and maximum score) of 0-48 (sum of all 12 items). The higher the score the better functioning. For the survival endpoint, the longer time the better outcome.; A patient's CAFS score represents a patient's rank in the study based on comparing the patient's outcome for both the change in ALSFRS-R and the time to death to all other patients in the study in a pairwise fashion. The ranked scores range from 001 to 189 (the number of subjects in the mITT population) with larger rank score numbers associated with a better outcome. The reported values are the mean rank scores in each group for the composite endpoint.	28 weeks following the first intrathecal injection