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

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)

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")

Study Overview

• Status: Unknown
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Biological: HYNRCS-Allo 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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Haengdang-dong, Seongdong-gu
    • Seoul, Haengdang-dong, Seongdong-gu, Korea, Republic of, 133-792
      • Hanyang University Seoul Hospital, Cell Therapy Center for Neurologic Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HYNRCS-Allo inj.; 2 cycles of HYNRCS-Allo inj. with 6 months interval through intrathecal injection. *1 cycle of HYNRCS-Allo inj. is 2 times administration with 28 days interval by intrathecal.	Biological: HYNRCS-Allo inj; The patients enrolled in the trial will be successively allocated into single cohort for HYNRCS-Allo inj., 1.0 X 10^6 cells/kg according to the protocol design.; Other Names: HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Incidence of any treatment related serious adverse events(SAE)	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
ALS-Functional rating scales(ALS-FRS)	12 months
Incidence & Degree of Adverse Events(AE)	12 months
PRA test to identify generation status of HLA antibody	12 months

Collaborators and Investigators

• Sponsor: Hanyang University Seoul Hospital
• Collaborators: Corestem, Inc.
• Investigators: Principal Investigator: Seung Hyun Kim, M.D.,Ph.D., Hanyang University

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2017
• Primary Completion (ACTUAL): March 25, 2019
• Study Completion (ANTICIPATED): October 1, 2021

Study Registration Dates

• First Submitted: July 9, 2017
• First Submitted That Met QC Criteria: July 9, 2017
• First Posted (ACTUAL): July 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 16, 2019
• Last Update Submitted That Met QC Criteria: May 14, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: ALS; Motor Neuron Disease; Neurodegenerative Disease; Neuromuscular Disease; Central Nervous System Disease; HLA-haplo matched allogenic bone marrow derived stem cells
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: HYNR-CS-Allo-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No