Safety and Tolerability of CS10BR05 Inj. in Subjects with Multiple System Atrophy

A Phase 1 Study to Evaluate the Safety and Tolerability of Autologous Bone Marrow Derived Mesenchymal Stem Cells in Subjects with Multiple System Atrophy

The purpose of conducting phase 1 trial is to evaluate the safety and tolerability of autologous bone marrow-derived mesenchymal stem cells(CS10BR05) in subjects with Multiple System Atrophy.

Evaluation of DLT by carotid artery(intra-arterial) injection according to dose-escalating in Multiple System Atrophy.

Study Overview

• Status: Completed
• Conditions: Multiple System Atrophy
• Intervention / Treatment: Biological: CS10BR05

Detailed Description

Multiple system atrophy is a neurodegenerative disease of the central nervous system which is accompanied by signs of autonomic imbalance (orthostatic hypotension, urinary problems, erectile dysfunction), Parkinson's symptoms (movement decreases, limb tremors) and cerebellar ataxia symptoms (grogginess, pronounced incorrectly). It shows signs similar to Parkinson's disease, however, it doesn't show improvement of symptoms by dopaminergic drugs and occurs at any age.

The clinical trial was designed as a single center, open-label, public phase 1 clinical trials.

If that subject's written consent to participate in this clinical trial will be conducted the required examinations and tests in accordance with the study protocol.

Then, the register for each dose step. For the final 3 subjects in the inclusion / exclusion criteria and be administered a drug test.

And check the adverse events for more than four hours after administration of the investigational drug, and will determine whether the expression of adverse drug reaction(ADR) by the visit after 1 days, 14 days and 28 days.

Except for dose administration, all subject are tested in the same schedule. As a result of evaluating severity of AE divided into subjective, objective in accordance with the CTCAE (Version 4.0) standards.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and Female patients aged ≥30 years and ≤ 75 years
• Meet criteria for diagnosis of probable MSA -cerebellar type according to the Gilman Criteria(2008)
• MRI or PET imaging showed a decrease in the cerebellar atrophy or cerebral metabolism
• Patients who are less than 4 years from the time of documented MSA diagnosis
• Patients unified MSA rating scale 30~50
• Those who have no hematologic abnormalities and who are not suspected of failing bone marrow function
• Patients who consented to participate in the study in writing by themselves or their legal representatives

Exclusion Criteria:

• Suspected clear Dementia (K-MMSE < 24)
• DSM-IV criteria for Dementia
• Radiologic imaging findings suggest that vascular encephalopathy coexist
• Other central nervous system diseases except MSA (Parkinsons disease etc.)
• Patients with Stroke or Brain surgery
• If there is a coexistence of severe medical illness, or if it is in a severe pyrexia state
• Serum SGOT / SGPT measures above three times of upper limit of normal or creatine levels were above 1.5 times of upper limit of normal levels were more than 1.5 times normal
• disease that affects the patient's long-term survival(Tumor, Serious Heart failure)
• Patients with genetic tests showed that spinocerebellar ataxia 1, 2, 3, 6, 7, 17
• Patients with unstable vital signs
• Patients with uncontrolled comorbidities such as moderate to severe infections, bleeding
• Those who are found to be active to viral infection(HBV, HCV, HIV, CMV, HTLVⅠ/Ⅱ, VDRL)
• Patients who are hypersensitive to bovine protein or antibiotics such as penicillin and streptomycin
• Patients with difficult catheter insertion(bleeding disorder, artery hardening narrowness, Patients who are at risk of stroke in cerebral angiography)
• Patients with cardiovascular disease(for example, hypertension, myocardial infarction etc;)
• Severe disease uncontrolled (diabetes)
• Those who are using drug likely to affect bone marrow functions
• Pregnant women or nursing women
• Women of childbearing age and male who do not consent to use proper contraception to prevent his partner from being pregnant during participation in the study
• Now clinical trials treated with other drugs and in clinical trials the previous 4 weeks
• Subjects who by the investigator to make them ineligible for participation in this clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CS10BR05; The single injection of CS10BR05 Inj. in the carotid artery	Biological: CS10BR05; The single injection of CS10BR05 Inj. in the carotid artery; Step 1 dose : 3.0x105cells/kg; Step 2 dose : 6.0x105cells/kg; Step 3 dose : 9.0x105cells/kg; The duration of follow up study following the single dose of CS10BR05 is 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicity and Maximum Tolerated Dose of CS10BR05 Inj.	To evaluate the safety and tolerability of CS10BR05 Inj. in patients with Multiple System Atrophy including determination of its Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD).	up to 28days
Adverse events, frequency and rate of vitals sign, laboratory test, physical examination, ECG, etc.	To evaluate the safety and tolerability of CS10BR05 Inj. in patients with Multiple System Atrophy.	up to 28days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unified Multiple System Atrophy Rating Scale(UMSARS)	Part I (Historical review), part II (Motor examination scale), part III (Autonomic examination), part IV (Global disability scale) assessment	-35days, 28days

Collaborators and Investigators

• Sponsor: Corestemchemon, Inc.
• Investigators: Principal Investigator: Phil Hyu Lee, M.D., Yonsei University

Publications and helpful links

Helpful Links

• Corestem Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2018
• Primary Completion (Actual): December 5, 2019
• Study Completion (Actual): December 5, 2019

Study Registration Dates

• First Submitted: August 6, 2017
• First Submitted That Met QC Criteria: August 25, 2017
• First Posted (Actual): August 29, 2017

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: MSA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Atrophy; Multiple System Atrophy; Shy-Drager Syndrome
• Other Study ID Numbers: CS10BR05-MSA101

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
• product manufactured in and exported from the U.S.: No