Autologous Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS)

March 7, 2018 updated by: Brainstorm-Cell Therapeutics

A Phase IIa, Open Label, Dose-escalating Clinical Study to Evaluate the Safety, Tolerability and Therapeutic Effects of Transplantation of Autologous Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS).

The study will evaluate the safety, tolerability and therapeutic effects of transplantation of escalating doses of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), in patients with amyotrophic lateral sclerosis (ALS).

Study Overview

Detailed Description

This is a phase IIa prospective, open label, dose-escalating, three patient-group clinical study, to evaluate the safety, tolerability and preliminary efficacy of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), as a potent treatment for patients with Amyotrophic Lateral Sclerosis (ALS) at the early disease stages. This study is a single center trial. It is anticipated that the study will be conducted at the Department of Neurology & Laboratory of Neuroimmunology, at the Hadassah Hebrew University Medical Center, Jerusalem in Israel. In addition, ALS patients could also be referred to the clinical site above by other medical centers.

All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients diagnosed as early stage ALS disease with duration of less than 2 years. ALS patients identified as "predisposed" will be approached and requested to sign an Informed Consent Form (ICF). Overall, 14 patients will be recruited.

Treatment will start with the lowest dose (94x106 cells) and the dose will be increased to the next medium and high dose (141x106 and 188x106 respectively), for the next patients group only following safety analysis.

The expected duration of patient screening period prior to enrollment into this study is in-between two weeks up to 2 days prior to the study enrollment day during visit 2 (verification of compliance with inclusion/exclusion criteria including clinical laboratory results). Eligible patients will be enrolled into the study and will be observed for every month during a "run in period" of 3 months for determination of the progression rate of the disease (allowing a time window of ± 5 days for all visits). During the "run in period" after about 6 weeks following enrollment, patients of both study groups will undergo a Bone Marrow Aspiration (BMA) procedure and MSC-NTF cells will be produced from the bone marrow aspirate based on Brainstorm Cell Therapeutics Ltd proprietary method. On the last "run in period" visit, patients will undergo the treatment and MSC-NTF will be transplanted by IM+IT to the early ALS patients.

After the MSC-NTF transplantation patients will be observed on a monthly basis for a post treatment follow up period of 6 months (allowing a time window of ± 5 days for all visits). Treatment safety, adverse events and exploratory parameters, to establish ALS progression rate assessment of the disease will be recorded throughout the duration of the "run in period" and the post treatment follow up period.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Jerusalem, Israel, 91120
        • Hadassah Medical Organization

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patient must fulfill El Escorial criteria (APPENDIX 2) for definite or probable ALS (sporadic and not familial)
  2. Participants, either men or non pregnant women are between 20 and 75 years of age.
  3. The patient is mentally intact and psychologically stable
  4. Patients will be with an ALS-FRS-R scale (APPENDIX 3) of at least 30 and disease duration of less than 2 years.
  5. Patient has sufficiently bulky muscles.
  6. Participant understands the nature of the procedure and provides written informed consent prior to any study procedure.

Exclusion Criteria:

  1. Patient has a positive test for HBV, HCV or HIV.
  2. Patient has high protein in the CSF (Protein > 70 mg/ml).
  3. Patient has lymphocytosis in the CSF (lymphocytes > 5/ml).
  4. Patient is positive for anti-GM1 antibodies.
  5. Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies.
  6. The patient is a respiratory dependent patient.
  7. Patients with renal failure (Cr > 2 mg/dl).
  8. Patients with impaired hepatic function (ALT, AST or GGT 2-fold higher than normal upper limit).
  9. Patients suffering from significant cardiac disease, malignant disease or any other disease that may risk the patient or interfere with the ability to interpret the results
  10. Patient with active infections.
  11. Participation in another clinical trial within 1 month prior to start of this study.
  12. Patient has not been treated previously with any cellular therapy.
  13. Subject unwilling or unable to comply with the requirements of the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety evaluation and tolerability of a single treatment administration in an escalating-dose of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF)
Time Frame: At baseline and up to 6 month following treatment administration
At baseline and up to 6 month following treatment administration

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale
Time Frame: At baseline and up to 6 month following treatment administration
At baseline and up to 6 month following treatment administration
Changes in muscle strength grading (MVIC) by muscle chart
Time Frame: At baseline and up to 6 month following treatment administration
At baseline and up to 6 month following treatment administration
Changes in muscle bulk estimated by MRI of the upper and lower extremities
Time Frame: At baseline and up to 6 month following treatment administration
At baseline and up to 6 month following treatment administration
Change in upper and lower extremities circumference (cm)
Time Frame: At baseline and up to 6 month following treatment administration
At baseline and up to 6 month following treatment administration
Changes in EMG parameters
Time Frame: At baseline and up to 6 month following treatment administration
At baseline and up to 6 month following treatment administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Dimitrios Karusis, MD, PhD, Hadassah Medical Organization

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 1, 2012

Primary Completion (ACTUAL)

September 1, 2014

Study Completion (ACTUAL)

September 1, 2015

Study Registration Dates

First Submitted

December 12, 2012

First Submitted That Met QC Criteria

January 24, 2013

First Posted (ESTIMATE)

January 29, 2013

Study Record Updates

Last Update Posted (ACTUAL)

March 8, 2018

Last Update Submitted That Met QC Criteria

March 7, 2018

Last Verified

March 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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