Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis

Hanyang University Seoul Hospital

Status and phase

Completed

Phase 1

Conditions

Motor Neuron Disease

Central Nervous System Disease

Amyotrophic Lateral Sclerosis

Neurodegenerative Disease

Neuromuscular Disease

Treatments

Genetic: HYNR-CS-Allo

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01758510

HYNR-CS-Allo-01

Details and patient eligibility

About

The purpose of this study is to evaluate the safety of HLA-haplo matched Allogenic Bone Marrow Derived stem cells("HYNR-CS-Allo inj"), through intrathecal delivery for the treatment in patients with amyotrophic lateral sclerosis(ALS).

This study is an open label, dose up and down study using the 3+3 design to assess the safety of HLA-haplo matched Allogenic Bone Marrow Derived stem cells("HYNR-CS-Allo inj")

Full description

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by motor neuron loss. Despite of many trials for disease-modifying, no treatment has so far changed natural course of disease.

The investigators had performed the pre-clinical and clinical studies using autologous bone marrow-derived stem cells in ALS. In the investigators' results of clinical trial, intrathecal injection of autologous bone marrow-derived stem cells is safe and could slow down disease progression and might be used as a disease modifying strategy in patients with ALS.

In the new field, like cell therapy, it is an important issue whether a bone marrow derived mesenchymal stem cells can be used as an allograft. Many investigators had showed that the immunoprivileged and immunosuppressive properties of mesenchymal stem cells result from the absence of major histocompatibility class II antigens and the secretion of T helper type 2 cytokines.

One potential advantage of allogenic bone marrow derived cells could be avoiding the need for procedural delay before treatment. And it is also hypothesized that the function of autologous bone marrow derived cells could be impaired in patients with co-morbidities or advanced age.

This study is to evaluate safety of HYNR-CS-Allo inj(HLA-haplo matched Allogenic bone marrow-derived stem cells) in patients with ALS.

The patients enrolled in the trial will be successively allocated into three cohorts for HYNR-CS-Allo inj., 0.25 X 10^6 cells/kg, 0.5 X 10^6 cells/kg, 1 X 10^6 cells/kg, according to the 3+3, up and down protocol design. The first treatment cohort will be 0.5 X 106 cells/kg dose cohort. Only a maximum of six patients will be given a particular dosage.

The scheduled assessments and visits will be carried out over three periods: run-in period, treatment period, and follow-up period.

The run-in period includes the screening visit where a written informed consent is obtained and the screening period where patients are assessed for eligibility. It will be completed within 30 days prior to enrollment. The patients meeting inclusion criteria will start the treatment period.

During the treatment period, subjects will be administered HYNR-CS-Allo inj. 2 times by intrathecal administration with 28 days interval.

The Follow-up period starts once subjects complete the treatment period and will continue until the final follow-up visit.

Enrollment

6 patients

Sex

All

Ages

25 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients between 25 and 80 years old
Patients who have both signs of lower motor neuron(LMN) and upper motor neuron(UMN) degeneration by clinical, electrophysiological or neuropathologic examination
Patients diagnosed as 'Probable' or 'Definite' ALS according to the World Federation of Neurology El Escorial criteria
Patients whose duration of disease is within 5 years from the first diagnosis
Patients with ALSFRS-R score within 21 to 46 at screening
Patients who can visit to a hospital by walk personally or by protector's help
Patients who provide the written consent by oneself or his/her legal representative
Patients who has HLA-haplo matched Bone marrow donor

Exclusion criteria

Patients who doesn't appropriate to the diagnostic criteria of ALS
Patients who are diagnosed as primary lateral sclerosis(PLS) or progressive muscular atrophy(PMA)
Patients suspected of adverse effect after stem cell injection(patients suspected of malignant tumor, risk group of psychogenic shock, patients with serious hypertension)
Patients with ALSFRS-R score below 21 at screening
Patients performed ventilator or tracheostomy at screening
Patients performed gastrostomy at screening
Patients unable to assess the efficacy of this clinical trial due to unattainable Pulmonary Functional Test(PFT) or patients with suspected 40% or less of Forced vital capacity(FVC) at screening
Patients with finding of myocardial infarction or angina pectoris according to ECG, patients who have been performed Stenting or Bypass operation at screening
Patients who have taken any other drug for clinical trial within the past 3 months at screening entry
Patients with epilepsy
Patients with severe renal dysfunction(serum creatinine≥2.0mg/dl)
Patients with severe liver dysfunction(ALT, AST, bilirubin≥upper limit of normal X 2)
Pregnant woman, lactating woman, female patients who has a pregnancy planning or who doesn't agree with adoption of contraception methods proper medically, male patients who doesn't agree with adoption of contraception methods proper to his partner during participating this study
Patients with hemorrhagic tendency at screening
Patients with virus infection at screening
Patients with a known history of hypersensitivity/allergy to penicillin and streptomycin
Patients with previous stem cell therapy
Patients diagnosed with cancer
Patients who have taken any drug that can effect to bone marrow function
Patients with any other neurological disease except ALS
Patients with psychotic diseases