- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02017912
Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study of Autologous MSC-NTF Cells in Patients With ALS (NurOwn)
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Massachusetts General Hospital
-
Worcester, Massachusetts, United States, 01655
- UMass Medical School
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
- 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.
Exclusion Criteria:
- 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 Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Autologous MSC-NTF cells
Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration
|
Single autologous MSC-NTF cells treatment by combined intramuscular and intrathecal administration
Other Names:
|
PLACEBO_COMPARATOR: Excipient
Combined intramuscular and intrathecal placebo administration
|
Excipient administration by combined intramuscular and intrathecal administration
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of patients with adverse events
Time Frame: At all study visits: Visit 1 through visit 10
|
At all study visits: Visit 1 through visit 10
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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
|
Visits 1,2,3,5,6,7,8,9,10
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Robert H Brown, D.Phil, M.D., UMass Medical School
- Principal Investigator: Anthony J. Windebank, M.D., Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BCT-001-US
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.
Clinical Trials on Amyotrophic Lateral Sclerosis (ALS)
-
Northwestern UniversityCompletedAmyotrophic Lateral Sclerosis (ALS) | Lou Gehrig's Disease | Primary Lateral Sclerosis (PLS) | Familial Amyotrophic Lateral Sclerosis | ALS With Frontotemporal Dementia (ALS/FTD) | Motor Neuron Disease (MND) | Sporadic ALS (SALS)United States
-
Dallas VA Medical CenterRecruitingAmyotrophic Lateral Sclerosis (ALS)United States
-
St. Joseph's Hospital and Medical Center, PhoenixEmory University; Mitsubishi Tanabe Pharma America Inc.Active, not recruitingALS (Amyotrophic Lateral Sclerosis)United States
-
Taipei Veterans General Hospital, TaiwanUnknownDevelopment and Needs Assessment and Efficiency of Smart Communication System for Patients With ALS.ALS (Amyotrophic Lateral Sclerosis)Taiwan
-
Phoenix Neurological Associates, LTDInstitute for EthnomedicineUnknown
-
Skulpt, Inc.National Institute of Neurological Disorders and Stroke (NINDS); National Institutes...CompletedAmyotrophic Lateral Sclerosis (ALS)United States
-
Neuromed IRCCSRecruitingAmyotrophic Lateral Sclerosis (ALS)Italy
-
Humanitas Mirasole SpAKU Leuven; UMC Utrecht; University of Sheffield; Istituto Superiore di Sanità; University... and other collaboratorsActive, not recruitingAmyotrophic Lateral Sclerosis (ALS)United Kingdom, Germany, France, Netherlands, Belgium, Ireland, Italy
-
The Methodist Hospital Research InstituteMassachusetts General Hospital; The Center for Clinical and Translational Sciences... and other collaboratorsActive, not recruiting
-
CytokineticsCompletedAmyotrophic Lateral Sclerosis (ALS)United States, Netherlands, Canada, Belgium, United Kingdom, France, Germany, Ireland, Italy, Portugal, Spain
Clinical Trials on Autologous MSC-NTF cells
-
Brainstorm-Cell TherapeuticsCompletedMultiple Sclerosis, Chronic ProgressiveUnited States
-
Brainstorm-Cell TherapeuticsNo longer availableAmyotrophic Lateral SclerosisUnited States
-
Brainstorm-Cell TherapeuticsHadassah Medical OrganizationCompletedAmyotrophic Lateral SclerosisIsrael
-
Brainstorm-Cell TherapeuticsCalifornia Institute for Regenerative Medicine (CIRM)CompletedAmyotrophic Lateral Sclerosis (ALS)United States
-
Dimitrios KarussisCompletedMultiple Sclerosis (MS)Israel
-
University Hospital, ToulouseThoratec CorporationWithdrawnChronic Myocardial IschemiaFrance
-
Mayo ClinicRegenerative Medicine MinnesotaTerminatedDiabetes Mellitus, Type 2 | Diabetes Mellitus, Type 1 | Diabetic Kidney Disease | Diabetic Nephropathies | Chronic Kidney Disease | Kidney Failure | Diabetic Nephropathy Type 2 | Kidney InsufficiencyUnited States
-
Mayo ClinicRecruiting
-
Mayo ClinicCompletedAtherosclerotic Renal Artery Stenosis | Ischemic Nephropathy | Renovascular HypertensionUnited States
-
University of BergenHaukeland University Hospital; University of Ulm; Université de NantesCompleted