Chondrochymal® for Subjects With Knee Osteoarthritis (Knee OA)

NCT ID: NCT05027581

Last Updated: 2025-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-13
• Study Completion Date: 2025-06-04

Brief Summary

This is a randomized, single-blind, parallel, active-controlled study to evaluate the efficacy and safety of bone marrow mesenchymal stem cells (BM-MSCs), Chondrochymal®, in subjects aged 40 to 80 with knee OA.

Detailed Description

This phase IIb study is a prospective, single-blind, parallel, active-controlled study to evaluate the efficacy and safety of Chondrochymal® in subjects with knee OA. All the subjects will be enrolled in Taiwan. The target population is composed of subjects with unilateral or bilateral OA knee(s). For subjects with bilateral OA knees, only the knee with more severe symptoms will be selected as the target knee. If the severities of the OA symptoms are the same for both knees, the knee with more pain should be selected, where the WOMAC pain score will take the priority over the VAS index. Eligible subjects will be randomized into one of the study groups, Chondrochymal® Group or Control Group, in 1:1 ratio. To keep the blindness, the subject's eyesight will be masked by a curtain while receiving the IA injection.

Conditions

Osteoarthritis, Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Chondrochymal® group

Subjects will be IA injected at the target knee with 3 mL of Chondrochymal® containing 5.0 x 107 BM-MSCs in lactated Ringer's solution at Day 1.

Group Type: EXPERIMENTAL

Bone marrow mesenchymal stem cells

Intervention Type: DRUG

The bone marrow mesenchymal stem cells (BM-MSCs) in Chondrochymal® for this study was obtained from the donor recruited in Taipei Veterans General Hospital, Taiwan. Donors aged 20 to 50 and tested negative to infection of human immunodeficiency virus type 1 and 2 (HIV-1/2), hepatitis B virus (HBV), hepatitis C virus (HCV), Cytomegalovirus (CMV), Treponema pallidum (syphilis), human T-lymphotropic virus types I and II (HTLV-I/II), and Tuberculosis (TB) were enrolled. The eligible donor's bone marrow was aspirated from the iliac crest or femur. The collected BM-MSCs were then cultured, expanded and cryopreserved in a Good Tissue Practice (GTP)-complied laboratory. The qualified cells in cryopreservation meeting the release criteria will be thawed, mixed with lactated Ringer's solution, and transferred into a sterile syringe as the final product.

Hya-Joint Plus Synovial Fluid Supplement

Hya-Joint Plus Synovial Fluid Supplement containing 60 mg/3 mL of hyaluronic acid will be IA administrated into the subject's target knee at Day 1.

Group Type: ACTIVE_COMPARATOR

hyaluronic acid

Intervention Type: DRUG

(60 mg/3 mL hyaluronic acid \[HA\])

Interventions

Bone marrow mesenchymal stem cells

The bone marrow mesenchymal stem cells (BM-MSCs) in Chondrochymal® for this study was obtained from the donor recruited in Taipei Veterans General Hospital, Taiwan. Donors aged 20 to 50 and tested negative to infection of human immunodeficiency virus type 1 and 2 (HIV-1/2), hepatitis B virus (HBV), hepatitis C virus (HCV), Cytomegalovirus (CMV), Treponema pallidum (syphilis), human T-lymphotropic virus types I and II (HTLV-I/II), and Tuberculosis (TB) were enrolled. The eligible donor's bone marrow was aspirated from the iliac crest or femur. The collected BM-MSCs were then cultured, expanded and cryopreserved in a Good Tissue Practice (GTP)-complied laboratory. The qualified cells in cryopreservation meeting the release criteria will be thawed, mixed with lactated Ringer's solution, and transferred into a sterile syringe as the final product.

Intervention Type: DRUG

hyaluronic acid

(60 mg/3 mL hyaluronic acid \[HA\])

Intervention Type: DRUG

Other Intervention Names

Chondrochymal®; Hya-Joint Plus Synovial Fluid Supplement

Eligibility Criteria

Inclusion Criteria

1. All genders aged 40 to 80 (inclusive).

2. WOMAC pain score equals to or higher than 7 in the target knee.

3. Subject with unilateral/bilateral OA knee(s) of Kellgren-Lawrence grading II-IV, who is not suitable for or unwilling to undergo knee surgery (including total knee replacement).

4. Pain of the target knee as assessed by Visual Analogue Scale (VAS) equals to or higher than 4.

5. Body mass index (BMI) between 20 and 35 kg/m2.

6. Has received conventional therapies for knee OA (e.g., analgesic administration or physical therapy) for more than 3 months but the symptoms have not relieved.

7. With adequate hematological indices: - White blood cell (WBC) ≥ 3,000/mm3 - Platelet count ≥ 80,000/μL - Prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) ≤ 1.5 times the upper limit of the normal range (ULN)

8. With adequate liver function where serum total bilirubin ≤ 1.5 times ULN, aspartate aminotransferase (AST) ≤ 3 times ULN, and alanine aminotransferase (ALT) ≤ 3 times ULN.

9. Has an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2, calculated by the Modification of Diet in Renal Disease (MDRD) equation.

10. Understand and sign the informed consent form.

Exclusion Criteria

1. With congenital or acquired bone hypoplasia (Varus more than 10° or Valgus more than 20°).

2. Had any intra-articular (IA) injection or surgery of the target knee within 3 months prior to screening, or had received any prior cell therapy on the target knee.

3. With severe knee osteoarthritis on the target knee who has decided to receive surgery (including total knee replacement) per surgeon's advice before screening.

4. With coagulation or hematological disorder not suitable for IA injection.

5. Administered or requiring systemic or topical on the target knee joint immunosuppressive agent, anti-inflammatory drug, steroid, analgesics, opioid, or duloxetine for knee OA, except for acetaminophen (oral daily dose ≤ 2000 mg or topical use at any dose level), Etoricoxib (oral daily dose ≤ 120 mg or topical use at any dose level), and Celebrex (oral daily dose ≤ 200 mg or topical use at any dose level), within 1 week prior to screening. For long-acting steroids (e.g., dexamethasone), a subject received systemic treatment within 2 weeks before screening will be excluded. A subject requiring routine use of low-dose Aspirin for preventing thrombosis (≤ 100 mg/day) will not be excluded from this study.

6. With spontaneous knee osteonecrosis on either knee.

7. With crippled lower limb(s) rated ACR functional class IV (Largely or Wholly Incapacitated) or cannot walk without one/two arm(s)-operated walking assisting device (defined by CNS15390).

8. With effusion, bleeding, ligament instability, arthrochalasis, muscular or neurological diseases causing deformity of the knee joint, or any joint diseases other than OA on the target knee.

9. Active systemic infection or acute infection around the target knee joint.

10. Any significant dermatological disease near the injection site that is not suitable for IA injection at the investigator's discretion.

11. Has claustrophobia and/or cannot take magnetic resonance imaging (MRI) test.

12. 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).

13. Previous surgery of the target knee that may cause metal imaging artifacts on imaging study.

14. Known or possible allergy to components of the study drugs or rescue medications.

15. Any form of primary immunodeficiency or autoimmune disease requiring systemic immunosuppressive therapy.

16. Subjects with malignant tumors or benign tumors that may interfere with the study treatment or subsequent evaluation.

17. Has serious medical conditions such as renal (estimated glomerular filtration rate < 30 mL/min/1.73m2), hepatic (e.g., Child-Pugh Class C), psychiatric condition (e.g., alcoholism, drug abuse), medical history, physical findings, or laboratory abnormality that in the investigators' opinion could interfere with the results of the trial or adversely affect the safety of the subject.

18. Currently with confirmed or suspected active infection of HIV, HBV, or HCV at the investigator's discretion.

19. Has received cytotoxic agent, chemotherapy, or radiotherapy that could interfere with the efficacy of investigational product within 3 months of the screening visit.

20. Had prior investigational therapy (including cell therapy) within the past 3 months prior to subject's Screening Visit.

21. Female subject of childbearing potential who:

• Is lactating; or
• Has positive pregnancy test result at eligibility checking; or
• Refuses to adopt at least one form of birth control from signing informed consent to the end of the study.

• Established use of oral, injected or implanted hormonal methods of contraception.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps).

23. Physiologically or psychologically inappropriate for participating in the study per investigator's judgment.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

A2 Healthcare Taiwan Corporation

INDUSTRY

Sponsor Role: collaborator

Taiwan Bio Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Taipei Veterans General Hospital

Taipei, Beitou District, Taiwan

Taipei Municipal Wangfang Hospital (Managed by Taipei Medical University)

Taipei, Wenshan District, Taiwan

Countries

Taiwan

Other Identifiers

Chondrochymal-01

Identifier Type: -

Identifier Source: org_study_id