Allogenic Adipose-Derived Mesenchymal Progenitor Cells for the Treatment of Knee Osteoarthritis

• ClinicalTrials.gov Identifier: NCT05996224
• Recruitment Status: Not yet recruiting
• First Posted: August 18, 2023
• Last Update Posted: August 18, 2023
• Sponsor: Cellular Biomedicine Group Ltd.
• Information provided by (Responsible Party): Cellular Biomedicine Group Ltd.

Study Description

Brief Summary:

Evaluate the efficacy and safety of Allogenic Adipose Tissue-Derived Mesenchymal Progenitor Cells Therapy

Condition or disease	Intervention/treatment	Phase
Knee Osteoarthritis	Biological: Mesenchymal progenitor cells; Drug: Sodium Hyaluronate Injection	Phase 3

Detailed Description:

A Multicenter, Randomized, Double-blind, Controlled Phase III Trial of Allogenic Adipose Tissue-Derived Mesenchymal Progenitor Cells (AlloJoin®) Therapy for Knee Osteoarthritis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 488 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Controlled Phase III Trial of Allogenic Adipose Tissue-Derived Mesenchymal Progenitor Cells (AlloJoin®) Therapy for Knee Osteoarthritis.
• Estimated Study Start Date: October 2023
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Mesenchymal progenitor cells; Mesenchymal progenitor cells group	Biological: Mesenchymal progenitor cells; Allogenic Adipose tissue-derived mesenchymal progenitor cells administrated for intra- articular use
Active Comparator: Sodium hyaluronate; Sodium hyaluronate injection group	Drug: Sodium Hyaluronate Injection; Sodium Hyaluronate administrated for intra-articular use; Other Name: Hyaluronic acid injection

Outcome Measures

Primary Outcome Measures :

1. WOMAC score [ Time Frame: 24 weeks ]
   The Western Ontario and McMaster Universities Osteoarthritis Index;0-96 points；96 points mean a worse outcome,will be tested at 24 weeks after the first injection

Secondary Outcome Measures :

1. MRI quantitative analysis of articular cartilage [ Time Frame: 48 weeks ]
   Magnetic Resonance Imaging analysis of articular cartilage, will be tested at 48 weeks after the first injection
2. WOMAC Score [ Time Frame: 4、12、24、36、48、60、72、84、96 weeks ]
   The Western Ontario and McMaster Universities Osteoarthritis Index;0-96 points；96 points mean a worse outcome, will be tested at 4、12、24、36、48、60、72、84 and 96 weeks after the first injection
3. VAS Score [ Time Frame: 4、12、24、36、48、60、72、84、96 weeks ]
   Visual Analogue Scale/Score；0-10 points；10 points mean the worse outcome,will be tested at 4、12、24、36、48、60、72、84 and 96 weeks after the first injection
4. SF-36 [ Time Frame: 4、12、24、36、48、60、72、84、96 weeks ]
   The Medical Outcomes Study 36-Item Short-Form Health Survey;0-100 points；100 points mean a better outcome, will be tested at 4、12、24、36、48、60、72、84 and 96 weeks after the first injection
5. MRI quantitative analysis of articular cartilage [ Time Frame: 24 weeks and 96 weeks ]
   Magnetic Resonance Imaging analysis of articular cartilage, will be tested at 24 and 96 weeks after the first injection
6. Whole-Organ Magnetic Resonance Imaging Score [ Time Frame: 24、48 and 96 weeks ]
   Whole-Organ Magnetic Resonance Imaging Score(WORMS) of the knee; 0-332points; 332 points means the worst outcome; will be assessed at 24、48 and 96 weeks
7. mJSW [ Time Frame: 96 weeks ]
   Minimum joint space width (mJSW) of the knee, will be measured at baseline and 96 weeks
8. Adverse Events and Serious Adverse Events [ Time Frame: Day 0 to 96 weeks ]
   AE and SAE, will be assessed within the 96 week time span
9. Physical examination [ Time Frame: Day 0、week 1、2、3、4、12、24、36、48、60、72、84、96 ]
   Height and weight will be tested and combined to report BMI in kg/m^2at Day 0 and week 1、2、3、4、12、24、36、48、60、72、84、96

Other Outcome Measures:

1. Inflammatory biomarkers detection [ Time Frame: Day 0 and week 4、12、24、36、48、96 ]
   Prostaglandin E2 in serum will be tested at Day 0 and week 4、12、24、36、48、96

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects who understand and voluntarily sign the consent form before this study；
2. According to the diagnostic criteria (American Rheumatology Association, clinical + radiology criteria), patients with knee osteoarthritis are definitely diagnosed；
3. Age: 40-75, males and females；
4. The course of knee osteoarthritis was more than 6 months;
5. The subjects' WOMAC score was 24-72, and the WOMAC pain score was 7-17 (the WOMAC score at least 48 hours after discontinuation of all painkillers);
6. The Kellgren Lawrence grade (X-ray axial position of knee joint) of subjects was grade II / III;
7. Subjects are generally in good condition and can walk autonomously, except for those who use wheelchairs, walking aids or crutches.

Exclusion Criteria:

1. The subject may be allergic to the main cell preparation components (B vitamins, amino acids and so on).
2. The subject received systemic and / or local treatment with autologous and / or allogeneic mesenchymal progenitor cells.
3. The subject has a BMI of over 30.
4. Laboratory test (any item meets): neutrophil absolute number < 1.0 × 10^9 / L, platelet count < 50 × 10^9 / L, serum albumin < 30g / L, serum creatinine > upper limit of 1.2 times normal value range, total bilirubin、alanine aminotransferase、aspartate aminotransferase > upper limit of 2 times of normal value range.
5. The subject has diseases or symptoms may affect VAS, WOMAC and so on.
6. The subject has serious and poorly controlled concomitant diseases, such as (but not limited to) nervous system, cardiovascular, liver, kidney, gastrointestinal and endocrine diseases, which may prevent the subjects from participating in the study according to the judgment of the researchers.
7. The subject has an history malignant tumour.
8. The subject has connective tissue disease or rheumatoid arthritis、chondropathy、Chondrocalcinosis articularis、 Hemochromatosis、inflammatory arthropathy、avascular necrosis of femoral head、Paget's disease、hemophilic arthropathy、infectional arthritis、Charcot' s disease、villonodular synovitis or synovial chondromatosis.
9. The subject has severe generalized infectious diseases or local knee infection (including skin and intra-articular infection) in the 3 months prior to this trial.
10. According to the researchers, the subject has disease of lower limbs which may be interfered knee evaluation, for example fibromyalgia, osphyalgia, lumbar disc protrusion and so on.
11. The subject had any other coagulation dysfunction caused by acute or chronic diseases, according to the judgment of the researchers, this coagulation dysfunction may endanger the safety of patients and / or affect the judgment of knee joint evaluation indicators.
12. The subject has received arthroscopic surgery or other open surgery related to knee joint operation in the 6 months prior to this trial.
13. The subject has received other intra-articular injections, including but not limited to hyaluronic acid, hormone, PRP, BMP (bone morphogenetic protein) , hypertonic glucose and so on for KOA in the 3 months preceding the trial.
14. The subject has received aminoglucose or chondroitin sulfate within 1 month before the treatment.
15. The subject has used dexamethasone, prednisone, hydrocortisone and other hormones orally / intravenously within 1 month before the treatment.
16. The subject has attenuated or live attenuated vaccine injection with 1 month before the treatment.
17. The subject has undergone knee prosthesis or a plan of knee prosthesis within the trial.
18. The subject has contraindication of MRI, included but not only: the subject installed heart pacemaker, defibrillator, heart bracket, heart valve prosthesis, metal clip after aneurysm surgery, drug infusion device implanted in vivo, any electronic device implanted in the body (nerve stimulator, bone growth stimulator) endovascular coil, strainer, ECG monitor, metal suture, shrapnel or sand of body, plate fixation and steel nail after fracture surgery, artificial cochlea, middle ear shift plant, metallic intraocular foreign body etc; the subject is a claustrophobia, critical ill patient and so on.
19. The subject tests positive for: HIV, HBV, HCV and treponema pallidum.
20. The subject has history of alcoholism, drug abuse, or mental illness in the 3 years prior to this trial.
21. The subject has participated in any other clinical trial in the 3 months prior to this trial.
22. The subject (including male subjects) has fertility, sperm donation or egg donation plans during the trial period; the female subject is pregnant, lactating or having a positive pregnancy test.
23. The subject is legally disabled by reference to the law of the people's Republic of China on the protection of disabled persons (April 2008).
24. The subject has any other unsuitable condition (such as factors reducing the follow-up compliance) to be determined by the investigator.
25. The Kellgren Lawrence grade (X-ray axial position of knee joint) of any knee joint of the subjects was grade IV.

Contacts and Locations

Contacts

Contact: Chunde Bao, M.D. & Ph.D.; M.D. & Ph.D.; xck@renji.com

Locations

China, Shanghai

Department of Rheumatology,Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,China

Shanghai, Shanghai, China, 200127

China

China-Japan Friendship Hospital

Beijing, China, 100029

The Second Affiliated hospital of Zhejiang University School of Medicine

Hangzhou, China, 310009

Huashan Hospital Affiliated to Fudan University

Shanghai, China, 200040

Shanghai General Hospital

Shanghai, China, 200080

Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine

Shanghai, China

Sponsors and Collaborators

Cellular Biomedicine Group Ltd.

More Information

• Responsible Party: Cellular Biomedicine Group Ltd.
• ClinicalTrials.gov Identifier: NCT05996224
• Other Study ID Numbers: CBM-MPC-007
• First Posted: August 18, 2023
• Last Update Posted: August 18, 2023
• Last Verified: August 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Hyaluronic Acid; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Viscosupplements; Protective Agents