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

• ClinicalTrials.gov Identifier: NCT04208646
• Recruitment Status: Recruiting
• First Posted: December 23, 2019
• Last Update Posted: November 4, 2020
• Sponsor: Cellular Biomedicine Group Ltd.
• Collaborators: RenJi Hospital; Shanghai 6th People's Hospital; Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Second Affiliated Hospital, School of Medicine, Zhejiang University; China-Japan Friendship Hospital; Huashan Hospital; Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
• 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; Biological: No mesenchymal progenitor cells	Phase 2

Detailed Description:

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

This is a multicenter, randomized, double-blinded, phase II clinical trial. Subjects who are with a clinical diagnosis of knee osteoarthritis cartilage defects and will be randomly distributed 1:1:1 to different group after signing the ICF and screening tests. Each group was treated for two cycles. The patients were followed up to 48 weeks after the first treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Controlled Phase II Trial of Allogenic Adipose Tissue-Derived Mesenchymal Progenitor Cells (AlloJoin®) for the Treatment of Knee Osteoarthritis
• Actual Study Start Date: May 16, 2020
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: January 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Mesenchymal progenitor cells Dosage 1; Mesenchymal progenitor cells low-dose group	Biological: Mesenchymal progenitor cells; Allogenic Adipose tissue-derived mesenchymal progentior cells administrated for intra- articular use
Experimental: Mesenchymal progenitor cells Dosage 2; Mesenchymal progenitor cells high-dose group	Biological: Mesenchymal progenitor cells; Allogenic Adipose tissue-derived mesenchymal progentior cells administrated for intra- articular use
Placebo Comparator: No mesenchymal progenitor cells; No mesenchymal progenitor cells	Biological: No mesenchymal progenitor cells; No mesenchymal progenitor cells for intra- articular use

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: 24 weeks,48 weeks ]
   Magnetic Resonance Imaging analysis of articular cartilage, will be tested at 24、48 weeks after the first injection
2. WOMAC Score [ Time Frame: 4、8、12、36、48 weeks ]
   The Western Ontario and McMaster Universities Osteoarthritis Index;0-96 points；96 points mean a worse outcome, will be tested at 4、8、12、36、48 weeks after the first injection
3. VAS Score [ Time Frame: 4、8、12、24、36、48 weeks ]
   Visual Analogue Scale/Score；0-10 points；10 points mean a worse outcome,will be tested at 4、8、12、24、36、48 weeks after the first injection
4. SF-36 [ Time Frame: 4、8、12、24、36、48 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、8、12、24、36、48 weeks after the first injection
5. Adverse Events and Serious Adverse Events [ Time Frame: 0d、1、3、4、8、12、24、25、27、28、36、48 weeks ]
   AE and SAE, will be assessed at 0d、1、3、4、8、12、24、25、27、28、36、48 weeks
6. Changes of laboratory test indexes and vital signs [ Time Frame: 0d、1、3、4、8、12、24、25、27、28、36、48 weeks ]
   Vital signs, physical examination, clinical laboratory tests:infectious disease check, blood coagulation test , blood check, urine check, blood biochemical test, immunological examination, tumor screening ,will be tested at 0d、1、3、4、8、12、24、25、27、28、36、48 weeks

Other Outcome Measures:

1. Metabolic index detection [ Time Frame: 0、4、8、12、24、36、48 weeks ]
   Levels of cartilage metabolism and inflammatory biomarkers in serum and urine will be tested at 0、4、8、12、24、36、48 weeks

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 and less than 10 years;
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 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 undergone knee prosthesis or a plan of knee prosthesis within the trial.
17. 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.
18. The subject tests positive for: HIV, HBV, HCV and treponema pallidum.
19. The subject has history of alcoholism, drug abuse, or mental illness in the 3 years prior to this trial.
20. The subject has participated in any other clinical trial in the 3 months prior to this trial.
21. 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.
22. 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).
23. The subject has any other unsuitable condition (such as factors reducing the follow-up compliance) to be determined by the investigator.

24.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.; 021-587523545; xck@renji.com

Locations

China

China-Japan Friendship Hospital; Recruiting

Beijing, China, 100029

Principal Investigator: Guochun Wang

The Second Affiliated hospital of Zhejiang University School of Medicine; Recruiting

Hangzhou, China, 310009

Principal Investigator: Shigui Yan

Huashan Hospital Affiliated to Fudan University; Recruiting

Shanghai, China, 200040

Contact: Weiguo Wan

Principal Investigator: Weiguo Wan

Shanghai General Hospital; Recruiting

Shanghai, China, 200080

Principal Investigator: Chengqing Yi

Shanghai Jiaotong University School of Medicine, Renji Hospital; Recruiting

Shanghai, China, 200127

Principal Investigator: Chunde Bao, MD

Shanghai Sixth People's Hospital; Recruiting

Shanghai, China, 200233

Principal Investigator: Changqing Zhang

Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine; Not yet recruiting

Shanghai, China

Principal Investigator: Jinwu Wang

Sponsors and Collaborators

Cellular Biomedicine Group Ltd.

RenJi Hospital

Shanghai 6th People's Hospital

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Second Affiliated Hospital, School of Medicine, Zhejiang University

China-Japan Friendship Hospital

Huashan Hospital

Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Investigators

• Principal Investigator: Chunde Bao; Shanghai Jiaotong University School of Medicine, Renji Hospital
• Principal Investigator: Changqing Zhang; Shanghai 6th People's Hospital
• Principal Investigator: Guochun Wang; China-Japan Friendship Hospital
• Principal Investigator: Chengqing Yi; Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Principal Investigator: Shigui Yan; Second Affiliated Hospital, School of Medicine, Zhejiang University
• Principal Investigator: Weiguo Wan; Huashan Hospital
• Principal Investigator: Jinwu Wang; Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

More Information

• Responsible Party: Cellular Biomedicine Group Ltd.
• ClinicalTrials.gov Identifier: NCT04208646
• Other Study ID Numbers: CBM-ALAM.1-01
• First Posted: December 23, 2019
• Last Update Posted: November 4, 2020
• Last Verified: November 2020

• 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