Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study of Autologous MSC-NTF Cells in Patients With ALS (NurOwn)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02017912
Recruitment Status : Completed
First Posted : December 23, 2013
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
Brainstorm-Cell Therapeutics

Tracking Information
First Submitted Date  ICMJE December 17, 2013
First Posted Date  ICMJE December 23, 2013
Last Update Posted Date July 18, 2018
Study Start Date  ICMJE May 2014
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2013)
Number of patients with adverse events [ Time Frame: At all study visits: Visit 1 through visit 10 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02017912 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2013)
  • Change in Amyotrophic Lateral Sclerosis (ALS) Functional Rating Scale (ALS-FRS) slopes from the pre-transplantation period to the post-transplantation period between the treatment and placebo groups through 24 weeks post-transplantation. [ Time Frame: At all study visits: Visit 1 through visit 10 ]
  • Change in SVC slopes from the pre-transplantation period to the post-transplantation period between the treatment and placebo groups through 24 weeks post-transplantation [ Time Frame: Visits 1,2,3,5,6,7,8,9,10 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2013)
  • Change in Amyotrophic Lateral Sclerosis (ALS) Functional Rating Scale (ALS-FRS) slopes from the pre-transplantation period to the post-transplantation period between the treatment and placebo groups through 24 weeks post-transplantation. [ Time Frame: At all study visits: Visit 1 through visit 10 ]
  • Change in SVC slopes from the pre-transplantation period to the post-transplantation period between the treatment and placebo groups through 24 weeks post-transplantation [ Time Frame: All visits (1 through 10) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study of Autologous MSC-NTF Cells in Patients With ALS
Official Title  ICMJE A Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study to Evaluate Safety and Efficacy of Transplantation of Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors (MSC-NTF) in Patients With ALS
Brief Summary

This is a multi-center, randomized, double blind, placebo controlled study to evaluate the safety and efficacy of autologous (self) transplantation of Neurotrophic factors-secreting Mesenchymal Stromal Cells (MSC-NTF, NurOwn™) in patients with ALS .

MSC-NTF cells are a novel cell-therapeutic approach which is expected to effectively deliver Neurotrophic factors, which are potent survival factors for neurons, directly to the site of damage.

Detailed Description

The MSC-NTF cell therapy (NurOwn™) is based on transplantation of autologous bone marrow derived mesenchymal stromal cells (MSC), which are enriched from the patients' own bone marrow, propagated ex vivo and induced to secrete NTFs. The autologous MSC-NTF cells are back-transplanted into the ALS patient into the sites of damage, the spinal cord and the muscles.

NTFs are potent survival factors for embryonic, neonatal, and adult neurons and are considered potential therapeutic candidates for ALS. Delivery of appropriate 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.

Previous open-label clinical trials have shown that MSC-NTF cells treatment was well tolerated and appears to be generally safe. Some initials indications of clinical benefit were also observed in some patients.

This multi-center, randomized, double blind, placebo controlled study will evaluate the safety and efficacy of a single combined intramuscular and intrathecal administration of MSC-NTF cells in early-stage ALS patients. Patients will be followed for approximately three months before transplantation with their autologous MSC-NTF cells or placebo. During this period of time, patient bone-marrow will be harvested and mesenchymal stromal cells will be isolated and expanded. Following treatment patients will be followed for a total of six months at monthly visits.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis (ALS)
Intervention  ICMJE
  • Biological: Autologous MSC-NTF cells
    Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration
    Other Name: NurOwn
  • Biological: Placebo
    Excipient administration by combined intramuscular and intrathecal administration
Study Arms  ICMJE
  • Active Comparator: Autologous MSC-NTF cells
    Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration
    Intervention: Biological: Autologous MSC-NTF cells
  • Placebo Comparator: Excipient
    Combined intramuscular and intrathecal placebo administration
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 17, 2013)
48
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2016
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Males and females ages 18 to 75 years old, inclusive.
  2. ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
  3. Disease onset, as defined by first reported occurrence of symptomatic weakness, spasticity, or bulbar symptoms, of more than 12 months and less than or equal to 24 months.
  4. Current disease symptoms must include limb weakness.
  5. ALSFRS-R ≥30 at the Screening Visit.
  6. Upright slow vital capacity (SVC) measure ≥65% of predicted for gender, height, and age at the Screening Visit.
  7. Subjects must be taking a stable dose of riluzole for at least 30 days prior to enrolment or not be on riluzole, and not have been on it for at least 30 days prior to enrolment (riluzole-naïve subjects are permitted in the study).
  8. Capable of providing informed consent and willing and able to follow study procedures, including willingness to undergo lumbar puncture.
  9. Geographic accessibility to the study site and willingness and ability to comply with follow-up.
  10. Women of child-bearing potential must agree not to become pregnant for the duration of the study. Women must be willing to consistently use two forms of contraceptive therapy throughout the course of the trial, and undergo a pregnancy test one week before bone marrow aspiration. Men must be willing to consistently use two forms of contraceptive if their partners are of child-bearing age.
  11. Citizen or permanent resident of the United States.

Exclusion Criteria:

  1. Prior stem cell therapy of any kind.
  2. Inability to lie flat for the duration of intrathecal cell transplantation and/or bone marrow biopsy, or inability to tolerate study procedures for any other reason.
  3. History of autoimmune disease (excluding thyroid disease) myelodysplastic or myeloproliferative disorder, leukemia or lymphoma, whole body irradiation, hip fracture, or severe scoliosis.
  4. Any unstable clinically significant medical condition other than ALS (e.g., within six months of baseline, had myocardial infarction, angina pectoris, and/or congestive heart failure), treatment with anticoagulants that, in the opinion of the investigator, would compromise the safety of patients.
  5. Any history of malignancy including any malignancy affecting the central nervous system and melanoma, within the previous 5 years, with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline).
  6. Serum AST or ALT value >3.0 times the upper normal limit.
  7. Serum creatinine value >2.0 times the upper normal limit.
  8. Positive test for Hepatitis B, Hepatitis C, HIV.
  9. Current use of immunosuppressant medication or use of such medication within 4 weeks of Screening visit (Visit 1).
  10. Any history of acquired or inherited immune deficiency syndrome.
  11. Exposure to any other experimental agent (off-label use or investigational) or participation in a clinical trial within 30 days prior to Screening Visit (Visit 1).
  12. Use of non-invasive ventilation (NIV), diaphragm pacing system or invasive ventilation (tracheostomy).
  13. Any history of either substance abuse within the past year, or unstable psychiatric disease according to PI judgment.
  14. Placement or usage of feeding tube.
  15. Pregnant women or women currently breastfeeding.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02017912
Other Study ID Numbers  ICMJE BCT-001-US
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Brainstorm-Cell Therapeutics
Study Sponsor  ICMJE Brainstorm-Cell Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Merit Cudkowicz, MD Massachusetts General Hospital
Principal Investigator: Robert H Brown, D.Phil, M.D. UMass Medical School
Principal Investigator: Anthony J. Windebank, M.D. Mayo Clinic
PRS Account Brainstorm-Cell Therapeutics
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP