Safety and Efficacy Study of Autologous Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis

March 15, 2022 updated by: Corestem, Inc.

An Open-label, Phase I/II Trial for Safety and Efficacy Study of Autologous Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis

The purpose of this study is to evaluate the safety and efficacy of autologous bone marrow-derived stem cells("HYNR-CS inj"), through intrathecal delivery for the treatment in patients with ALS.

This study consists of 2 steps. First step is a safety study of the intrathecal(IT) injection of "HYNR-CS inj" in 8 patients with ALS. In this phase 1 study, AE, laboratory test, physical examination, vital signs, Electrocardiogram, and Chest X-Ray examination were evaluated in terms of safety.

Second step is to compare the efficacy and safety between test group and control group of total 64 patients with ALS.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

We have performed the pre-clinical and clinical studies using autologous bone marrow-derived stem cells in ALS. We could get the evidence that autologous bone marrow-derived stem cells have dose-dependent effects on SOD1 mice via intrathecal injection. In our results of clinical trial, intrathecal injection of autologous bone marrow-derived stem cells could slow down disease progression and might be used as a disease modifying strategy in patients with ALS.

This study was designed as a single center, randomized, open-label, parallel-group, 2-stage study, and targeted at patients diagnosed with Amyotrophic Lateral Sclerosis(Lou Gehrig's disease). The study consisted of Stage-1 study for safety evaluation and Stage-2 study for efficacy and safety evaluation of the study drug, and at Stage 1, 7 subjects eligible for the inclusion/exclusion criteria received safety evaluation for 28 days of study drug administration in twice under the protocol, and then followed Stage 2. To decide whether the study can be proceeded in 2 stages, ADR(CTCAE Version 3.0, ≥grade 3) should not appear in initial 7 subjects.

Data obtained from subjects of this study were analyzed into three: Safety Analysis, ITT(Intent-To-Treat) Analysis, and PP(Per Protocol) Analysis. However, in case of phase 1, only safety analysis was conducted, and in case of phase 2, all of safety, ITT, and PP analyses were conducted.

For ITT Analysis, all the subjects whose data on primary efficacy endpoint could be obtained following the administration of investigational drug were analyzed in analysis among subjects who were administered the investigational drug once at least. Also, Modified ITT Analysis, including 7 subjects at Stage 1, was carried out.

Study Type

Interventional

Enrollment (Actual)

72

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients between 25 and 75 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 who have taken Rilutek at stable background dose from 3 months ago at least before screening entry
  • Patients whose duration of disease is within 5 years from the first diagnosis
  • Patients with ALSFRS-R score within 31 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

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 30 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 PFT(Pulmonary Functional Test) or patients with suspected 40% or less of 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 thag can effect to bone marrow function
  • Patients with any other neurological disease except ALS
  • Patients with psychotic diseases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Test group
Treatment group with HYNR-CS inj.
Biological: HYNR-CS inj
Intrathecal injection with 1ml/10kg of body weight at an interval of 26 days.
EXPERIMENTAL: Control group
No treatment with HYNR-CS inj.
Other: Control group
No treatment of HYNR-CS inj

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Difference in the Changes of Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Between Treatment Groups and Control Groups.
Time Frame: baseline(Visit 5) and week 16(Visit 9)
ALSFRS-R is ordinal rating scale questionnaire (rating 0-4 for each question, 4 is most functional, 0-48 total) of 12 functional activities. The most functional total score is 48. ALSFRS-R was evaluated at baseline and week 28.(The first injection was performed at 0 week) ALSFRS-R total score variation baseline(Visit 5) and week 16(Visit 9)
baseline(Visit 5) and week 16(Visit 9)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Appel Scale
Time Frame: baseline(Visit 5) and week 16(Visit 9)

To evaluate the disease change, Appel scale will be assessed. Appel scale is a test tool, which is devised to evaluate the functional condition and variation of ALS(Lou Gehrig's disease) patients (rating 6 to between 30 and 36 points for each of 5 functional conditions, 30-164 total).

The higher the total score presents more severe disability. This was done at Visit 1, Visit 5 and Visit 9 (week -12,0,16). The first injection was performed at 0 week(Visit 5) Appel scale total score variation baseline(Visit 5) and week 16(Visit 9)
baseline(Visit 5) and week 16(Visit 9)
Change in Forced Vital Capacity (FVC) (Percent of Predicted Normal)
Time Frame: baseline(Visit 5) and week 16(Visit 9)

Secondary efficacy was measured by comparing the rate of decline of mean FVC by treatment group.

FVC which is a clinical scale to observe variation in patient's respiratory competence, was conducted at Visit 1, Visit 5 and Visit 9. (week -12,0,16) The first injection was performed at 0 week. FVC variation baseline(Visit 5) and week 16(Visit 9)
baseline(Visit 5) and week 16(Visit 9)
Change in SF-36 (The Short Form (36) Health Survey is a 36 Item)
Time Frame: baseline(Visit 5) and week 16(Visit 9)

The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score presents more severe disability. The higher the score presents less disability.

This was measured at Visit 5 and Visit 9. (week 0,16) The first injection was performed at 0 week.

The score variation baseline(Visit 5) and week 16(Visit 9)
baseline(Visit 5) and week 16(Visit 9)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Corestem, Inc.

Investigators

  • Principal Investigator: Seung Hyun Kim, M.D., Ph.D., Hanyang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (ACTUAL)

May 1, 2013

Study Completion (ACTUAL)

August 1, 2013

Study Registration Dates

First Submitted

May 30, 2011

First Submitted That Met QC Criteria

May 30, 2011

First Posted (ESTIMATE)

June 1, 2011

Study Record Updates

Last Update Posted (ACTUAL)

March 17, 2022

Last Update Submitted That Met QC Criteria

March 15, 2022

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HYNR_CS_ALS201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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