Clinical trial NCT03214146: Safety/Efficacy Study of 2nd Cycle Treatment After 6 Months of 1st Cycle HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in ALS
Official title: An Open-label, Phase 1 Trial for Safety and Efficacy Study of 2nd Cycle Treatment After 6 Months of 1st Cycle HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell("HYNR-CS-Allo Inj") Treatment in Amyotrophic Lateral Sclerosis(ALS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Motor Neuron Disease
Neuromuscular Disease
Neurodegenerative Disease
Central Nervous System Disease
HLA-haplo matched allogenic bone marrow derived stem cells
Lead sponsor: Hanyang University Seoul Hospital
Sponsor class: OTHER
Collaborators: name: Corestemchemon, Inc.
First posted: 2017-07-11
Enrollment: 6
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of HLA-haplo matched Allogenic Bone Marrow Derived stem cells("HYNRCS-Allo-ALS-02 inj"), through intrathecal delivery for the repeated treatment after 6 months of first treatment in patients with amyotrophic lateral sclerosis(ALS).

This study is an open label, single-dose study to assess the safety and efficacy of HLA-haplo matched Allogenic Bone Marrow Derived stem cells("HYNRCS-Allo-ALS-02 inj")

Detailed 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 and efficacy of repeated treatment after 6 months of first HYNRCS-Allo-ALS-02 inj(HLA-haplo matched Allogenic bone marrow-derived stem cells) treatment in patients with ALS.

The patients enrolled in the trial will be successively allocated into single cohort for HYNRCS-Allo-ALS-02 inj., 1.0 X 10\^6 cells/kg, according to the protocol design. 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 56 days prior to enrollment. The patients meeting inclusion criteria will start the treatment period.

During the treatment period, subjects will be administered HYNRCS-Allo-ALS-02 inj. 2 times(first treatment) by intrathecal administration with 28 days interval and there will be repeated treatment after 6 months of the first treatment.

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

Eligibility criteria: Inclusion Criteria:

* Patients between 25 and 80 years old
* Patients diagnosed as 'Possible with lab-supported' or 'Possible' or '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 doesn't have HLA-haplo-matched bone marrow donor
* 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 Tracheostomy at screening
* Patients with suspected 20% or less of Forced vital capacity(FVC) at screening
* Patients who doesn't agree with written consent form by oneself of his/her legal representative
* Patients who have taken any other drug for clinical trial within the past 3 months at screening entry
* Patients with epilepsy
* Patients with severe medical disease
* 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 a known history of hypersensitivity/allergy to penicillin and streptomycin
* Patients with severe psychotic diseases (such as alzheimer, schizophrenia excepts slight cognitive dysfunction and secondary emotional disorder)

Primary outcomes:
measure: The Incidence of any treatment related serious adverse events(SAE)
timeFrame: 12 months
Secondary outcomes:
measure: ALS-Functional rating scales(ALS-FRS)
timeFrame: 12 months
measure: Incidence & Degree of Adverse Events(AE)
timeFrame: 12 months
measure: PRA test to identify generation status of HLA antibody
timeFrame: 12 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital, Cell Therapy Center for Neurologic Disorders
state: Haengdang-dong, Seongdong-gu
Study officials:
affiliation: Hanyang University
name: Seung Hyun Kim, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: