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

NCT02017912 | Completed Phase 2 Results DMC

• 1 other identifier: BCT-001-US
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

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.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Mesenchymal Stromal cells; MSC-NTF; Cell therapy; ALS

Outcome Measures

Primary Outcomes (1)

• Number of Patients With at Least One Treatment Emergent Adverse Events

  Safety assessed based on the incidence of treatment-emergent adverse events (TEAEs) (including serious adverse events \[SAEs\]) including clinically relevant changes in vital signs, clinical laboratory assessments, physical and neurological examinations, and electrocardiogram (ECG) tests, during transplantation of expanded autologous MSC-NTF cells administered on a single occasion via combined intrathecal (IT) administration and intramuscular (IM) injections

  Up to 24 weeks following the first intrathecal injection, or End of Study

Secondary Outcomes (2)

• Change in Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) Slopes From the Pre-transplantation Period to the Post-transplantation Period Between the Treatment and Placebo Groups Through 24 Weeks Post-transplantation.

  Up to 24 weeks following the first intrathecal injection

• 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

  Up to 24 weeks following the first intrathecal injection

Study Arms (2)

Nurown MSC-NTF cells

ACTIVE COMPARATOR

Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration

Biological: Nurown MSC-NTF cells

Excipient

PLACEBO COMPARATOR

Combined intramuscular and intrathecal placebo administration

Biological: Placebo

Interventions

Nurown MSC-NTF cells BIOLOGICAL

Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration

Also known as: NurOwn

Nurown MSC-NTF cells

Placebo BIOLOGICAL

Excipient administration by combined intramuscular and intrathecal administration

Excipient

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ages 18 to 75 years old, inclusive.
• ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
• 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.
• Current disease symptoms must include limb weakness.
• ALSFRS-R ≥30 at the Screening Visit.
• Upright slow vital capacity (SVC) measure ≥65% of predicted for gender, height, and age at the Screening Visit.
• 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).
• Capable of providing informed consent and willing and able to follow study procedures, including willingness to undergo lumbar puncture.
• Geographic accessibility to the study site and willingness and ability to comply with follow-up.
• 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.
• Citizen or permanent resident of the United States.

You may not qualify if:

• Prior stem cell therapy of any kind.
• 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.
• History of autoimmune disease (excluding thyroid disease) myelodysplastic or myeloproliferative disorder, leukemia or lymphoma, whole body irradiation, hip fracture, or severe scoliosis.
• 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.
• 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).
• Serum AST or ALT value \>3.0 times the upper normal limit.
• Serum creatinine value \>2.0 times the upper normal limit.
• Positive test for Hepatitis B, Hepatitis C, HIV.
• Current use of immunosuppressant medication or use of such medication within 4 weeks of Screening visit (Visit 1).
• Any history of acquired or inherited immune deficiency syndrome.
• 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).
• Use of non-invasive ventilation (NIV), diaphragm pacing system or invasive ventilation (tracheostomy).
• Any history of either substance abuse within the past year, or unstable psychiatric disease according to PI judgment.
• Placement or usage of feeding tube.
• Pregnant women or women currently breastfeeding.

Sponsors & Collaborators

• Brainstorm-Cell Therapeutics: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

UMass Medical School

Worcester, Massachusetts, 01655, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Brainstorm Cell Therapeutics

ClinicalTrial@brainstorm-cell.com

+1-201-488-0460

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2013
• First Posted: December 23, 2013
• Study Start: May 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: July 1, 2016
• Last Updated: June 6, 2024
• Results First Posted: June 6, 2024

Record last verified: 2024-05

Locations

US (3)