Back to results

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

Primary Purpose

Amyotrophic Lateral Sclerosis (ALS)

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

NurOwn® (MSC-NTF cells)

Placebo

Bone Marrow aspiration

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis (ALS) focused on measuring MSC, Autologous, Neurotrophic factors

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of California Irvine Alpha Stem Cell Clinic
Cedars-Sinai Medical Center
California Pacific Medical Center
Massachusetts General Hospital
University of Massachusetts Medical School
Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

NurOwn® (MSC-NTF cells)

Placebo

Arm Description

Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals

Three Intrathecal administrations of Placebo at bi-monthly intervals

Outcomes

Primary Outcome Measures

To evaluate the efficacy and safety of NurOwn® (autologous MSC-NTF cells) as compared to placebo as measured by the amyotrophic lateral sclerosis functional rating scale (ALSFRS-R)

To determine efficacy and safety of repeat intrathecal injections of NurOwn® as compared to Placebo given three times two months apart to participants with Amyotrophic Lateral Sclerosis

Secondary Outcome Measures

Biomarkers

To evaluate biomarkers (such as cell-secreted neurothrophic factors, inflammatory factors, and cytokines in pg/ml) in the cerebrospinal fluid (CSF) as well as in serum samples throughout the study to evaluate their relationship to treatment with NurOwn® (MSC-NTF cells)

Full Information

NCT ID

NCT03280056

First Posted

August 29, 2017

Last Updated

October 5, 2021

Sponsor

Brainstorm-Cell Therapeutics

Collaborators

California Institute for Regenerative Medicine (CIRM)

1. Study Identification

Unique Protocol Identification Number

NCT03280056

Brief Title

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

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

August 28, 2017 (Actual)

Primary Completion Date

October 30, 2020 (Actual)

Study Completion Date

October 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Brainstorm-Cell Therapeutics

Collaborators

California Institute for Regenerative Medicine (CIRM)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis (ALS)

Keywords

MSC, Autologous, Neurotrophic factors

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Randomized, Double-Blind, Placebo-Controlled Multicenter Study

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

This is a double-blind study where the investigators, participants and all sponsor and CRO personnel involved in the conduct, data management or analysis of the study will remain blinded to the treatment assignments

Allocation

Randomized

Enrollment

263 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NurOwn® (MSC-NTF cells)

Arm Type

Active Comparator

Arm Description

Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Three Intrathecal administrations of Placebo at bi-monthly intervals

Intervention Type

Biological

Intervention Name(s)

NurOwn® (MSC-NTF cells)

Intervention Description

Autologous transplantation of bone marrow derived mesenchymal stem cells propagated ex vivo and induced to secrete neurotrophic factors

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo

Intervention Type

Other

Intervention Name(s)

Bone Marrow aspiration

Intervention Description

Bone Marrow aspiration

Primary Outcome Measure Information:

Title

To evaluate the efficacy and safety of NurOwn® (autologous MSC-NTF cells) as compared to placebo as measured by the amyotrophic lateral sclerosis functional rating scale (ALSFRS-R)

Description

To determine efficacy and safety of repeat intrathecal injections of NurOwn® as compared to Placebo given three times two months apart to participants with Amyotrophic Lateral Sclerosis

Time Frame

28 weeks following the first treatment

Secondary Outcome Measure Information:

Title

Biomarkers

Description

Time Frame

Through selected post-treatment time points up to 20 weeks post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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

Overall Study Officials: