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Allogeneic Bone Marrow MSC Therapy for Knee Osteoarthritis

Primary Purpose

Knee Osteoarthritis

Status

Completed

Phase

Phase 1

Locations

Taiwan

Study Type

Interventional

Intervention

Chondrochymal®

About this trial

This is an interventional treatment trial for Knee Osteoarthritis focused on measuring Intra-articular (IA), Allogeneic, MSC, OA

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female at least 40 years old, completing the informed consent process for participating the clinical trial
Patients diagnosed with unilateral/bilateral knee osteoarthritis of grade II, III and IV (Kellgren and Lawrence scale) as assessed by doctors, who are not suitable for, or not willing to undergo knee surgery (including total knee replacement)
Pain of the knee as assessed by visual analogue scale (VAS) to be 4 or higher (VAS ≥ 4)
Body mass index (BMI) between 20 and 35 kg/m2
Neither local/systemic bacteremia nor acute infection around the knee joint

Exclusion Criteria:

Physiologically or psychologically inappropriate for participating the trial as evaluated by the investigators
Patients with congenital or acquired bone hypoplasia (Varus more than 10o or Valgus more than 20o)
BMI less than 20 or more than 35 (Class II obesity)
Female who is pregnant or breastfeeding, or in childbearing age; male or female subjects who are not able to use appropriate contraception methods during the trial
Patients with muscular or neurological diseases causing deformity of the targeted knee joint(s), which might interfere with the evaluation of trial.
Patients with malignant tumors, or benign tumors that may interfere with the trial treatment or subsequent evaluation.
Immunocompromised or patients suffering from immune diseases under long-term immuno-suppressive medication such as steroids, however, topical steroid is not included
Patients with coagulation or hematological disorders not suitable for intra-articular (IA) injection
Known or possible allergy to components in the product under trial
Patients had any IA injection or surgery of the targeted knee within the last 3 months
Patients with crippled lower limbs rated ACR functional class IV (Largely or Wholly Incapacitated) or cannot walk without one/two arms-operated walking assisting device (defined by CNS15390)
Spontaneous knee osteonecrosis
Previous surgery of the knee that may cause metal imaging artifacts on imaging study
Patients have claustrophobia and/or cannot take magnetic resonance imaging (MRI) test
Any metal devices placed in the body such as pacemaker, artificial heart valve, or hemostatic clamps/clips for intracranial aneurysm posing risk under magnetic field (of MRI)
Patients with severe unilateral (or bilateral) knee osteoarthritis who have decided to receive surgery (including total knee replacement) on the affected knee (or both knees if bilateral) after advised by their surgeon.
Having participated other clinical trials with medications (including cellular therapy) within the past 3 months prior to subject screening

Sites / Locations

Taipei Veterans General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Chondrochymal® 1 x 10^7 cells

Chondrochymal® 5 x 10^7 cells

Chondrochymal® 10 x 10^7 cells

Arm Description

At this stage, 3 patients with knee OA will be treated by the cell products of this dose.

Outcomes

Primary Outcome Measures

Number of participants with adverse events as measure of safety and tolerability

treatment-related adverse events assessed by CTCAE v4.0

Secondary Outcome Measures

Efficacy - Radiographic evidence

Change in cartilage thickness of the knee using MRI and X-ray

Efficacy - WOMAC assessment

Change in joint function from baseline WOMAC assessment

Efficacy - Visual Analogue Scale(VAS) assessment

The Visual Analog Scale (VAS) is a unidimensional measure of pain intensity. The scale is most commonly anchored by "no pain " (score of 0) and "worst imaginable pain" (score of 10).

Efficacy - Lequesne Index assessment

Change in arthritis pain scores on the Lequesne Index

Efficacy - Keen Society Score(KSS) assessment

The knee society score is divided into four parts: it consists of the ''Symptoms''(25 points), the ''Patient satisfaction''(40 points), the ''Patient expectation''(15 points) and the ''Functional activities''(100 points). Each part will be evaluated separately.

Efficacy - QOL assessment

Change in scores on the QOL

Full Information

NCT ID

NCT03589287

First Posted

June 4, 2018

Last Updated

August 17, 2021

Sponsor

Taipei Veterans General Hospital, Taiwan

Collaborators

Virginia Contract Research Organization Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03589287

Brief Title

Allogeneic Bone Marrow MSC Therapy for Knee Osteoarthritis

Official Title

A Phase I/IIa Clinical Study of Treatment for Knee Osteoarthritis by Intra-articular Injection of Allogeneic Bone Marrow Derived Mesenchymal Stem Cells.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

May 2, 2018 (Actual)

Primary Completion Date

May 3, 2019 (Actual)

Study Completion Date

April 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Taipei Veterans General Hospital, Taiwan

Collaborators

Virginia Contract Research Organization Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The Clinical trial is a phase I/IIa clinical study for treatment of knee osteoarthritis by intra-articular injection of bone marrow derived allogeneic mesenchymal stem cells. Primary endpoint of the study is safety of allogeneic BM-MSCs application on knee OA with single dose IA injection and the MTD. Secondary endpoint is the effect of allogeneic BM-MSCs transplantation including clinical and image observation since the MSCs have multi-lineage differentiation potential such as chondrocyte differentiation, anti-inflammation and immune-modulation.

Detailed Description

Osteoarthritis of the knee (Knee Osteoarthritis, Knee OA) is a joint disease that primarily affects cartilage. Cartilage is the smooth tissue covering the ends of bones within the joint. In people who suffer from knee OA, articular cartilage top is broken down and worn away, resulting in the underlying bones to rub against each other. This friction can cause pain, joint swelling and decreased range of motion (ROM). Eventually, the joint may become deformed and bone spurs may form around the edges. With the advances in biotechnology, cell therapy in the application of cartilage reconstruction has gradually matured. The purpose of this study is to assess the safety and efficacy of single intra-articular (IA) injection of allogeneic bone marrow (BM) mesenchymal stem cells (MSCs) for knee OA. The same cell products used in this trial have been applied in a phase I/IIa clinical trial in Taiwan for the treatment of critical limb ischemia, and so far no treatment-related adverse effect has been observed. In the current trial, allogeneic bone marrow MSCs of up to 4 donors will be isolated. BM MSCs are expanded and applied for a phase I/IIa study in treating 15-24 recipient patients with knee OA. The treatment protocol consists of two stages: the first stage is a traditional 3+3 open dose-escalated study design with three cohorts of dosing groups: (1) 1 x 10^7 cells, (2) 5 x 10^7 cells and (3) 10 x 10^7 cells. At the second stage, knee OA patients will be treated by the cell products of the maximum tolerance dose (MTD) as determined by the results of the first stage. All the study subjects will be followed up to 6 months (24 weeks) after the treatment for safety and preliminary efficacy evaluation, which the latter will include both clinical and imaging study assessments.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Knee Osteoarthritis

Keywords

Intra-articular (IA), Allogeneic, MSC, OA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Model Description

The treatment protocol consists of two stages: the first stage is a traditional 3+3 dose-escalation open study design with three cohorts. At the second stage, a total of 6 patients with knee OA will be treated by the cell products of the maximum tolerance dose (MTD) as determined by the results of the first stage.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Chondrochymal® 1 x 10^7 cells

Arm Type

Experimental

Arm Description

At this stage, 3 patients with knee OA will be treated by the cell products of this dose.

Arm Title

Chondrochymal® 5 x 10^7 cells

Arm Type

Experimental

Arm Description

At this stage, 3 patients with knee OA will be treated by the cell products of this dose.

Arm Title

Chondrochymal® 10 x 10^7 cells

Arm Type

Experimental

Arm Description

At this stage, 3 patients with knee OA will be treated by the cell products of this dose.

Intervention Type

Biological

Intervention Name(s)

Chondrochymal®

Intervention Description

Allogeneic Bone Marrow Derived Mesenchymal Stem Cells

Primary Outcome Measure Information:

Title

Number of participants with adverse events as measure of safety and tolerability

Description

treatment-related adverse events assessed by CTCAE v4.0

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Efficacy - Radiographic evidence

Description

Change in cartilage thickness of the knee using MRI and X-ray

Time Frame

24 weeks

Title

Efficacy - WOMAC assessment

Description

Change in joint function from baseline WOMAC assessment

Time Frame

24 weeks

Title

Efficacy - Visual Analogue Scale(VAS) assessment

Description

The Visual Analog Scale (VAS) is a unidimensional measure of pain intensity. The scale is most commonly anchored by "no pain " (score of 0) and "worst imaginable pain" (score of 10).

Time Frame

24 weeks

Title

Efficacy - Lequesne Index assessment

Description

Change in arthritis pain scores on the Lequesne Index

Time Frame

24 weeks

Title

Efficacy - Keen Society Score(KSS) assessment

Description

Time Frame

24 weeks

Title

Efficacy - QOL assessment

Description

Change in scores on the QOL

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female at least 40 years old, completing the informed consent process for participating the clinical trial Patients diagnosed with unilateral/bilateral knee osteoarthritis of grade II, III and IV (Kellgren and Lawrence scale) as assessed by doctors, who are not suitable for, or not willing to undergo knee surgery (including total knee replacement) Pain of the knee as assessed by visual analogue scale (VAS) to be 4 or higher (VAS ≥ 4) Body mass index (BMI) between 20 and 35 kg/m2 Neither local/systemic bacteremia nor acute infection around the knee joint Exclusion Criteria: Physiologically or psychologically inappropriate for participating the trial as evaluated by the investigators Patients with congenital or acquired bone hypoplasia (Varus more than 10o or Valgus more than 20o) BMI less than 20 or more than 35 (Class II obesity) Female who is pregnant or breastfeeding, or in childbearing age; male or female subjects who are not able to use appropriate contraception methods during the trial Patients with muscular or neurological diseases causing deformity of the targeted knee joint(s), which might interfere with the evaluation of trial. Patients with malignant tumors, or benign tumors that may interfere with the trial treatment or subsequent evaluation. Immunocompromised or patients suffering from immune diseases under long-term immuno-suppressive medication such as steroids, however, topical steroid is not included Patients with coagulation or hematological disorders not suitable for intra-articular (IA) injection Known or possible allergy to components in the product under trial Patients had any IA injection or surgery of the targeted knee within the last 3 months Patients with crippled lower limbs rated ACR functional class IV (Largely or Wholly Incapacitated) or cannot walk without one/two arms-operated walking assisting device (defined by CNS15390) Spontaneous knee osteonecrosis Previous surgery of the knee that may cause metal imaging artifacts on imaging study Patients have claustrophobia and/or cannot take magnetic resonance imaging (MRI) test Any metal devices placed in the body such as pacemaker, artificial heart valve, or hemostatic clamps/clips for intracranial aneurysm posing risk under magnetic field (of MRI) Patients with severe unilateral (or bilateral) knee osteoarthritis who have decided to receive surgery (including total knee replacement) on the affected knee (or both knees if bilateral) after advised by their surgeon. Having participated other clinical trials with medications (including cellular therapy) within the past 3 months prior to subject screening

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ming-Chau Chang, MD

Organizational Affiliation

Taipei Veterans General Hospital, Taiwan

Official's Role

Principal Investigator

Facility Information:

Facility Name

Taipei Veterans General Hospital

City

Taipei

Country

Taiwan

12. IPD Sharing Statement

Learn more about this trial

Allogeneic Bone Marrow MSC Therapy for Knee Osteoarthritis

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