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

NCT01758510 | Completed Phase 1 DMC

• 1 other identifier: HYNR-CS-Allo-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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")

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Neurodegenerative Disease; Central Nervous System Disease

Keywords

Amyotrophic Lateral Sclerosis; ALS; Neurodegenerative disease; Motor Neuron Disease; Central Nervous System Disease; Neuromuscular Disease; Bone marrow derived stem cell; stem cell therapy; intrathecal injection

Outcome Measures

Primary Outcomes (1)

• Serious Adverse Events(SAE)

  The Incidence of any treatment related serious adverse events(SAE)

  6 months

Secondary Outcomes (2)

• ALS-Functional rating scales(ALS-FRS)

  6 months

• Adverse Events(AE)

  6 months

Study Arms (1)

HYNR-CS-Allo

EXPERIMENTAL

HYNR-CS-Allo inj. 2 times by intrathecal administration with 28 days interval.

Genetic: HYNR-CS-Allo

Interventions

HYNR-CS-Allo GENETIC

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 10\^6 cells/kg dose cohort.

HYNR-CS-Allo

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hanyang University Seoul Hospital: lead
• Corestemchemon, Inc.: collaborator

Study Sites (1)

Hanyang University Seoul Hospital, Cell Therapy Center for Neurologic Disorders

Seoul, Haengdang-dong, Seongdong-gu, 133-792, South Korea

Location

Related Publications (9)

• Kwon MJ, Baek W, Ki CS, Kim HY, Koh SH, Kim JW, Kim SH. Screening of the SOD1, FUS, TARDBP, ANG, and OPTN mutations in Korean patients with familial and sporadic ALS. Neurobiol Aging. 2012 May;33(5):1017.e17-23. doi: 10.1016/j.neurobiolaging.2011.12.003. Epub 2012 Jan 15.

  PMID: 22244934 BACKGROUND

• Koh SH, Baik W, Noh MY, Cho GW, Kim HY, Kim KS, Kim SH. The functional deficiency of bone marrow mesenchymal stromal cells in ALS patients is proportional to disease progression rate. Exp Neurol. 2012 Jan;233(1):472-80. doi: 10.1016/j.expneurol.2011.11.021. Epub 2011 Nov 19.

  PMID: 22119626 BACKGROUND

• Koh SH, Huh YM, Noh MY, Kim HY, Kim KS, Lee ES, Ko HJ, Cho GW, Yoo AR, Song HT, Hwang S, Lee K, Haam S, Frank JA, Suh JS, Kim SH. beta-PIX is critical for transplanted mesenchymal stromal cell migration. Stem Cells Dev. 2012 Jul 20;21(11):1989-99. doi: 10.1089/scd.2011.0430. Epub 2012 Jan 26.

  PMID: 22087847 BACKGROUND

• Choi MR, Kim HY, Park JY, Lee TY, Baik CS, Chai YG, Jung KH, Park KS, Roh W, Kim KS, Kim SH. Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis. Neurosci Lett. 2010 Mar 19;472(2):94-8. doi: 10.1016/j.neulet.2010.01.054. Epub 2010 Feb 1.

  PMID: 20117176 BACKGROUND

• Cho GW, Noh MY, Kim HY, Koh SH, Kim KS, Kim SH. Bone marrow-derived stromal cells from amyotrophic lateral sclerosis patients have diminished stem cell capacity. Stem Cells Dev. 2010 Jul;19(7):1035-42. doi: 10.1089/scd.2009.0453.

  PMID: 20030561 BACKGROUND

• Kim H, Kim HY, Choi MR, Hwang S, Nam KH, Kim HC, Han JS, Kim KS, Yoon HS, Kim SH. Dose-dependent efficacy of ALS-human mesenchymal stem cells transplantation into cisterna magna in SOD1-G93A ALS mice. Neurosci Lett. 2010 Jan 14;468(3):190-4. doi: 10.1016/j.neulet.2009.10.074. Epub 2009 Oct 29.

  PMID: 19879334 BACKGROUND

• Kwon MS, Noh MY, Oh KW, Cho KA, Kang BY, Kim KS, Kim YS, Kim SH. The immunomodulatory effects of human mesenchymal stem cells on peripheral blood mononuclear cells in ALS patients. J Neurochem. 2014 Oct;131(2):206-18. doi: 10.1111/jnc.12814. Epub 2014 Jul 31.

  PMID: 24995608 BACKGROUND

• Oh KW, Moon C, Kim HY, Oh SI, Park J, Lee JH, Chang IY, Kim KS, Kim SH. Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis. Stem Cells Transl Med. 2015 Jun;4(6):590-7. doi: 10.5966/sctm.2014-0212. Epub 2015 May 1.

  PMID: 25934946 BACKGROUND

• Kim HY, Kim H, Oh KW, Oh SI, Koh SH, Baik W, Noh MY, Kim KS, Kim SH. Biological markers of mesenchymal stromal cells as predictors of response to autologous stem cell transplantation in patients with amyotrophic lateral sclerosis: an investigator-initiated trial and in vivo study. Stem Cells. 2014 Oct;32(10):2724-31. doi: 10.1002/stem.1770.

  PMID: 24966156 BACKGROUND

Related Links

• collaborator and stem cell provider
• home page of dementia center in Seoul Seongdong-gu

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Diseases; Neurodegenerative Diseases; Central Nervous System Diseases

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Seung Hyun Kim, M.D., Ph.D

  Hanyang University Seoul Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor/Dept. Neurology, College of Medicine, Hanyang University Seoul Hospital

Study Record Dates

• First Submitted: December 10, 2012
• First Posted: January 1, 2013
• Study Start: December 1, 2012
• Primary Completion: April 10, 2017
• Study Completion: April 10, 2017
• Last Updated: May 16, 2019

Record last verified: 2019-05

Locations

KR (1)