Autologous Adipose Tissue-Derived Mesenchymal Stem Cells (AdMSCs) for Osteoarthritis

Study Overview
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Brief Summary
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This is a phase 2 open-label, 6 arms (1 study group and 1 control group for each joint category), randomized control group clinical study with 300 subjects diagnosed with osteoarthritis of knees (n=100), hips (n=100) and shoulders (n=100). The study subjects will be evaluated for disease-associated severity according to symptoms, such as pain, mobility, daily active life, and functions using arthritis society established specific measurement tools related to the joints (KOOS and KSS for OA-knees: HOOS and HHS for OA-hips and ASES and CSS for OA-shoulders).

Official Title
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Clinical Study for Subjects With Osteoarthritis of Knees, Hips, and Shoulders Using a Combination of Intravenous Infusions With Intra-articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells (AdMSCs)

Conditions
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Osteoarthritis, Knee, Osteoarthritis, Hip, Osteoarthritis Shoulder

Intervention / Treatment
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* Biological: Celltex- AdMSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age above 18 years Male or female Subjects in study group must have banked AdMSCs at Celltex (already passed communicable disease screen tests for HIV, syphilis and Hepatitis B and C during banking stage) Must understand and voluntarily sign an Informed Consent for study participation obtained prior to undergoing any study-specific procedures Must be diagnosed as OA-knees, OA-hips, or OA-shoulders by radiographic criteria and physical examination. Exclusion Criteria: Participation in another clinical study (with use of another Investigational Medical Product) within 3 months prior to study treatment start Unwillingness or inability to comply with study procedures Patients with serious basic diseases that affect survival, including blood diseases, cachexia, active bleeding, severe malnutrition, etc. Clinically active malignant disease Previous thrombotic disorder History of known pulmonary embolism or known secondary anti-phospholipid syndrome Known or suspected hypersensitivity to any components used to culture the AdMSCs, e.g. BSA and sulfur-containing products (e.g., DMSO) Major trauma or surgery within 14 days of study treatment start Mental condition rendering the subject (or the subject's legally acceptable representative[s]) unable to understand the nature, scope and possible consequences of the study Alcohol, drug, or medication abuse within one year prior to study treatment start Any condition that, in the Investigator's opinion, is likely to interfere with evaluation of the AdMSC therapy or satisfactory conduct of the study Irreversible severe end-organ failure, such as heart failure/attack, stroke, liver and renal failure due to other disease conditions Patients or family history with a hypercoagulable status, such as protein C/protein S deficiency, factor V Leiden, prothrombin gene mutation, dysfibrinogenemia, etc. History of long-term use of immunosuppressive agents Organ transplants in the previous 6 months Pregnant, breastfeeding, or desire to become pregnant or unwilling to practice birth control during participation in the study duration, unless surgically sterilized or postmenopausal during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The Phase 2 study is an open-label, 6 arms, randomized, control group clinical study conducted in multiple clinical facilities.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2 Arm 1 - OA Knee<br>50 subjects receive two doses of 2.0-2.86 x 10^6 cells/kg on days 0 and 6 via intravenous infusion. On day 3, each subject will receive a single dose of 1.0-2.86 x 10^6 cells/kg via intra-articular injection into the injured joint. | Biological: Celltex- AdMSCs<br>* Autologous adipose-derived stem cells Culture expanded mesenchymal stem cells isolated from a patient's own abdominal fat tissue<br>* Other names: AdMSCs;|
| Active Comparator: Phase 2 Arm 2 OA Knee<br>Control group- 50 subjects receive three doses of 2.0-2.86 x 10^6 cells/kg on day 0, 3, and 6 via intravenous infusion | Biological: Celltex- AdMSCs<br>* Autologous adipose-derived stem cells Culture expanded mesenchymal stem cells isolated from a patient's own abdominal fat tissue<br>* Other names: AdMSCs;|
| Experimental: Phase 2 Arm 3 - OA Hip<br>50 subjects receive two doses of 2.0-2.86 x 10^6 cells/kg on days 0 and 6 via intravenous infusion. On day 3, each subject will receive a single dose of 1.0-2.86 x 10^6 cells/kg via intra-articular injection into the injured joint. | Biological: Celltex- AdMSCs<br>* Autologous adipose-derived stem cells Culture expanded mesenchymal stem cells isolated from a patient's own abdominal fat tissue<br>* Other names: AdMSCs;|
| Active Comparator: Phase 2 Arm 4 - OA Hip<br>Control group- 50 subjects receive three doses of 2.0-2.86 x 10^6 cells/kg on day 0, 3, and 6 via intravenous infusion | Biological: Celltex- AdMSCs<br>* Autologous adipose-derived stem cells Culture expanded mesenchymal stem cells isolated from a patient's own abdominal fat tissue<br>* Other names: AdMSCs;|
| Experimental: Phase 2 Arm 5 - OA Shoulder<br>50 subjects receive two doses of 2.0-2.86 x 10^6 cells/kg on days 0 and 6 via intravenous infusion. On day 3, each subject will receive a single dose of 1.0-2.86 x 10^6 cells/kg via intra-articular injection into the injured joint. | Biological: Celltex- AdMSCs<br>* Autologous adipose-derived stem cells Culture expanded mesenchymal stem cells isolated from a patient's own abdominal fat tissue<br>* Other names: AdMSCs;|
| Active Comparator: Phase 2 Arm 6 - OA Shoulder<br>Control group- 50 subjects receive three doses of 2.0-2.86 x 10^6 cells/kg on day 0, 3, and 6 via intravenous infusion | Biological: Celltex- AdMSCs<br>* Autologous adipose-derived stem cells Culture expanded mesenchymal stem cells isolated from a patient's own abdominal fat tissue<br>* Other names: AdMSCs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the frequency and nature of adverse events occurring during the study based on the annualized rate of all AdMSC-associated adverse events (AEs) in all subjects. | safety | 12 months | 
| Any organ damage or safety concerns determined by SMAC 20 blood test. | Safety | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Knee injury and Osteoarthritis Outcome Score (KOOS, 0 is the worst and 100 is the best) from the baseline for OA-knee patients | efficacy | 12 months | 
| Change of Knee Society Score (KSS, 0 is the worst and 100 is the best) from the baseline for OA-knee patients | efficacy | 12 months | 
| Change of Hip disability and Osteoarthritis Outcome Score (HOOS, 0 is the worst and 100 is the best) from the baseline for OA-hip patients | efficacy | 12 months | 
| Change of Harris Hip Score (HHS, 0 is the worst and 100 is the best) from the baseline for OA-hip patients | efficacy | 12 months | 
| Change of the American Shoulder and Elbow Surgeons Shoulder Score (ASES, 0 is the worst and 100 is the best) from the baseline for OA-shoulder patients | efficacy | 12 month | 
| Change of Constant shoulder score (CSS, 0 is the worst and 100 is the best) from the baseline for OA-shoulder patients | efficacy | 12 months | 
| changes in joint images (X-ray or MRI) from the baseline | efficacy | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous Adipose-derived Stem Cells (AdMSCs)