Chondrochymal® for Subjects With Knee Osteoarthritis (Knee OA)

A Phase IIb Study to Evaluate the Efficacy and Safety of Chondrochymal® for Subjects With Knee Osteoarthritis (Knee OA)

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.

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.

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.

22. Male subject with female spouse/partner who is of childbearing potential refuses to adopt at least one form of birth control from signing informed consent to the end of the study. For exclusion criteria #21 and #22, acceptable forms of birth control include:

    • 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.