Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study of Autologous MSC-NTF Cells in Patients With ALS
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Interventions
- Biological: PlaceboBiological: Nurown MSC-NTF cells
- Registration Number
- NCT02017912
- Lead Sponsor
- Brainstorm-Cell Therapeutics
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
Not provided
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Excipient Placebo Combined intramuscular and intrathecal placebo administration Nurown MSC-NTF cells Nurown MSC-NTF cells Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration
- Primary Outcome Measures
Name Time Method Number of Patients With at Least One Treatment Emergent Adverse Events Up to 24 weeks following the first intrathecal injection, or End of Study 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
- Secondary Outcome Measures
Name Time Method 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 The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. The total score of ALSFRS-R ranges from 0-48, with higher score being better. The slope of ALSFRS-R for the pre- and post-treatment is obtained from a linear regression model using all available data points in the corresponding period, respectively. The change in slope is obtained from a fixed-effect linear model which is defined as the post-treatment slope minus the pre-treatment slope. The unit of the slope is score on a scale per month. A positive change in slope, means that the patient's decline in the ALSFRS-R score is slower than pre-treatment. A negative change in slope, means that the patient decline in the ALSFRS-R score is faster than pre-treatment.
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 SVC measures the maximum amount of air exhaled in a single breath, this lung function is influenced by gender, height, and age, in a complex, non-linear, way.
The SVC reported is a normalized value obtained from a non-linear prediction model that accounts for the influence of participant's gender, height and age.
SVC was done 3 times at each visit, in order to capture and report the maximal, effort-dependent, lung function that a participant can deliver. The slope of SVC is obtained from a linear regression model using all available data points in the corresponding period, respectively. The change in slope is from a fixed-effect linear model which is defined as the post-treatment slope minus the pre-treatment slope. The unit of the slope is score on a scale per month.
Positive change in slope, means that the patient's decline in the SVC score is slower than pre-treatment.
Negative change in slope, means that the patient decline in the SVC score is faster than pre-treatment.
Trial Locations
- Locations (3)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
UMass Medical School
🇺🇸Worcester, Massachusetts, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
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