History of Changes for Study: NCT03280056

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

Latest version (submitted February 5, 2024) on ClinicalTrials.gov

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Study Record Versions

Version	Submitted Date	Changes
1	September 10, 2017	None (earliest Version on record)
2	September 15, 2017	Contacts/Locations and Study Status
3	December 5, 2017	Contacts/Locations, Eligibility and Study Status
4	March 6, 2018	Contacts/Locations and Study Status
5	March 7, 2018	Contacts/Locations and Study Status
6	May 24, 2018	Eligibility and Study Status
7	November 29, 2018	Contacts/Locations and Study Status
8	March 24, 2019	Study Status
9	July 4, 2019	Study Status
10	October 22, 2019	Recruitment Status, Study Status, Contacts/Locations and Study Design
11	January 25, 2021	Recruitment Status and Study Status
12	October 3, 2021	Study Status and Study Design
13	October 5, 2021	Arms and Interventions and Study Status
14	December 1, 2023	Quality Control Review has not concluded Returned: December 20, 2023 Study Status, Outcome Measures, Document Section, Adverse Events, Baseline Characteristics, Participant Flow, Arms and Interventions and Study Design
15	January 4, 2024	Quality Control Review has not concluded Returned: January 4, 2024 Study Status, Outcome Measures, Baseline Characteristics and Participant Flow
16	January 9, 2024	Quality Control Review has not concluded Returned: January 31, 2024 Outcome Measures and Study Status
17	February 5, 2024	Study Status, Outcome Measures and More Information

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Study NCT03280056
Submitted Date: September 10, 2017 (v1)

Study Identification


Unique Protocol ID:	BCT-002-US
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
Secondary IDs:

Study Status


Record Verification:	August 2017
Overall Status:	Recruiting
Study Start:	August 28, 2017
Primary Completion:	April 30, 2019 [Anticipated]
Study Completion:	July 30, 2019 [Anticipated]

First Submitted:	August 29, 2017
First Submitted that Met QC Criteria:	September 10, 2017
First Posted:	September 12, 2017 [Actual]

Last Update Submitted that Met QC Criteria:	September 10, 2017
Last Update Posted:	September 12, 2017 [Actual]

Sponsor/Collaborators


Sponsor:	Brainstorm-Cell Therapeutics
Responsible Party:	Sponsor
Collaborators:	California Institute for Regenerative Medicine (CIRM)

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

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
	Randomized, Double-Blind, Placebo-Controlled Multicenter Study
Number of Arms:	2
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	200 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Active Comparator: NurOwn® (MSC-NTF cells) Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals	Biological: NurOwn® (MSC-NTF cells) Autologous transplantation of bone marrow derived mesenchymal stem cells propagated ex vivo and induced to secrete neurotrophic factors
Placebo Comparator: Placebo Three Intrathecal administrations of Placebo at bi-monthly intervals	Placebo Placebo

Outcome Measures


Primary Outcome Measures:
1.	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) [ Time Frame: 28 weeks following the first treatment ] 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:
1.	Biomarkers [ Time Frame: Through selected post-treatment time points up to 20 weeks post transplant ] 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)

Eligibility


Minimum Age:	18 Years
Maximum Age:	60 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
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. Participants taking a stable dose of Riluzole are permitted in the study Exclusion Criteria: Prior stem cell therapy of any kind History of autoimmune or other serious disease (including malignancy and immune deficiency) 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

Contacts/Locations


Central Contact Person:	Ralph Z Kern, MD Telephone: 917-692-0091 Email: rkern@brainstorm-cell.com
Central Contact Backup:	Yael D Gothelf, Ph.D. Telephone: 646-666-3188 Ext. 102 Email: ygothelf@brainstorm-cell.com
Study Officials:	Merit E Cudkowicz, MD Principal Investigator Massachusetts General Hospital
	Robert H Brown, MD, PhD Principal Investigator UMass Medical School
	Anthony J. Windebank, MD Principal Investigator Mayo Clinic
	Namit A Goyal, MD Principal Investigator UC Irvine
	Robert G Miller, MD Principal Investigator California Pacific Medical Center (CPM) Research Institute
Locations:	United States, Massachusetts
	Massachusetts General Hospital [Recruiting] Boston, Massachusetts, United States, 02115 Contact:Contact: Taylor J Mezoian 617-643-0312 TMEZOIAN@mgh.harvard.edu Contact:Principal Investigator: James D Berry, MD

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