- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03589287
Allogeneic Bone Marrow MSC Therapy for Knee Osteoarthritis
August 17, 2021 updated by: Taipei Veterans General Hospital, Taiwan
A Phase I/IIa Clinical Study of Treatment for Knee Osteoarthritis by Intra-articular Injection of Allogeneic Bone Marrow Derived Mesenchymal Stem Cells.
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.
Study Overview
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.
Study Type
Interventional
Enrollment (Actual)
18
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
-
-
-
Taipei, Taiwan
- Taipei Veterans General Hospital
-
-
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
38 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
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: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Chondrochymal® 1 x 10^7 cells
At this stage, 3 patients with knee OA will be treated by the cell products of this dose.
|
Allogeneic Bone Marrow Derived Mesenchymal Stem Cells
|
Experimental: Chondrochymal® 5 x 10^7 cells
At this stage, 3 patients with knee OA will be treated by the cell products of this dose.
|
Allogeneic Bone Marrow Derived Mesenchymal Stem Cells
|
Experimental: Chondrochymal® 10 x 10^7 cells
At this stage, 3 patients with knee OA will be treated by the cell products of this dose.
|
Allogeneic Bone Marrow Derived Mesenchymal Stem Cells
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with adverse events as measure of safety and tolerability
Time Frame: 24 weeks
|
treatment-related adverse events assessed by CTCAE v4.0
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy - Radiographic evidence
Time Frame: 24 weeks
|
Change in cartilage thickness of the knee using MRI and X-ray
|
24 weeks
|
Efficacy - WOMAC assessment
Time Frame: 24 weeks
|
Change in joint function from baseline WOMAC assessment
|
24 weeks
|
Efficacy - Visual Analogue Scale(VAS) assessment
Time Frame: 24 weeks
|
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).
|
24 weeks
|
Efficacy - Lequesne Index assessment
Time Frame: 24 weeks
|
Change in arthritis pain scores on the Lequesne Index
|
24 weeks
|
Efficacy - Keen Society Score(KSS) assessment
Time Frame: 24 weeks
|
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.
|
24 weeks
|
Efficacy - QOL assessment
Time Frame: 24 weeks
|
Change in scores on the QOL
|
24 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
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 (Actual)
May 2, 2018
Primary Completion (Actual)
May 3, 2019
Study Completion (Actual)
April 30, 2020
Study Registration Dates
First Submitted
June 4, 2018
First Submitted That Met QC Criteria
July 16, 2018
First Posted (Actual)
July 17, 2018
Study Record Updates
Last Update Posted (Actual)
August 19, 2021
Last Update Submitted That Met QC Criteria
August 17, 2021
Last Verified
August 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2016-11-006C
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Knee Osteoarthritis
-
LifeBridge HealthMicroPort Orthopedics Inc.; Rubin Institute for Advanced OrthopedicsRecruitingKnee Osteoarthritis | Osteoarthritis, Knee | Knee Pain Chronic | Arthropathy of Knee Joint | Knee Disease | Osteoarthritis Knees Both | Osteoarthritis Knee Left | Osteoarthritis Knee RightUnited States
-
University Hospital, Clermont-FerrandSanofiCompletedKnee Osteoarthritis (Knee OA)France
-
Joseph E. BroylesCompletedDegenerative Lesion of Articular Cartilage of Knee | Degeneration; Articular Cartilage, Knee | Unilateral Primary Osteoarthritis of Knee | Osteoarthritis Knee
-
Jiangsu XinChen-Techfields Pharma Co., LTD.Completed
-
The Hong Kong Polytechnic UniversityCompleted
-
Federal University of São PauloCompletedKNEE OSTEOARTHRITISBrazil
-
Tianjin XinChen-Techfields Pharma Co., LTD.Completed
-
Eun Jung KimMinistry of Health & Welfare, Korea; Semyung UniversityUnknownOsteoarthritis KneeKorea, Republic of
-
Novartis PharmaceuticalsRecruitingSymptomatic Knee OsteoarthritisUnited States, Spain, Hungary, Argentina, Germany, Slovakia, Czechia, Belgium, Romania
-
University of BathUniversity of Oxford; 3D Metal Printing Ltd; Versus ArthritisRecruitingMedial Knee OsteoarthritisUnited Kingdom
Clinical Trials on Chondrochymal®
-
Taiwan Bio Therapeutics Co., Ltd.A2 Healthcare Taiwan CorporationActive, not recruiting
-
Dong-A ST Co., Ltd.CompletedFunctional DyspepsiaKorea, Republic of
-
Galderma R&DCompletedAtopic DermatitisPhilippines, China
-
Chong Kun Dang PharmaceuticalCompleted
-
Chung-Ang University Hosptial, Chung-Ang University...UnknownFunctional DyspepsiaKorea, Republic of
-
Sanofi Pasteur, a Sanofi CompanyCompletedPertussis | Diphtheria | PolioUnited States
-
Amir AzarpazhoohInstitut Straumann AGCompletedPeriodontal Inflammation | Crown LengtheningCanada
-
Novartis PharmaceuticalsCompletedPulmonary Disease, Chronic Obstructive (COPD)Argentina
-
GuerbetCompletedPrimary Brain TumorColombia, Korea, Republic of, United States, Mexico