Pivotal Study to Evaluate Efficacy and Safety of SP5M002 Inj. as Compared to Synovian Inj. in Patients With Mild to Moderate Knee Osteoarthritis

A Multi-center, Randomized, Double-Blinded, Active Controlled, Phase III Study to Evaluate Efficacy and Safety of SP5M002 Injection Compared With Synovian Injection in Patients With Mild to Moderate Knee Osteoarthritis

This is a randomized, double-blind, multicenter, Active Controlled, pivotal clinical trial to assess the efficacy and safety of the novel hexamethylenediamine (HMDA) cross-linked hyaluronate intra-articular injection (SP5M002) compared with an active comparator, the 1,4-butanediol diglycidyl ether (BDDE) cross-linked hyaluronate (Synovian) in patients with knee osteoarthritis.

Inclusion Criteria:

1. Adult males and females aged 40 years or older as of the date of written consent

2. Subject with knee osteoarthritis whose X-ray test results within 6 months from the screening or at the screening visit correspond to grades I - III of the Kellgren & Lawrence scale

3. Subject diagnosed with unilateral or bilateral knee osteoarthritis according to the clinical diagnostic criteria of the American College of Rheumatology (ACR) at screening who have knee joint pain and meet three or more of the following conditions

   • Over 50 years of age

     • Less than 30 minutes of morning stiffness ③ Crepitus on active motion ④ Bony tenderness ⑤ Bony enlargement ⑥ No palpable warmth of synovium

4. Weight bearing pain (WBP) of at least one of both knee joints on 100 mm-VAS ≥ 40 mm when measured at screening and baseline [However, if both sides have symptoms, the knee joint with the higher WBP becomes the joint for evaluation, and the selected joint cannot be changed during the study period.]

5. Walk without relying on a walking aid such as a walker or cane (patients who have been using a walking aid every day since 6 months prior to the screening visit can use the walking aid, and must use the walking aid in the same way throughout the study period.)

6. Ability to fully understand and complete the safety and efficacy measurement questionnaire

7. Voluntary decision for participation and provision of written consent to comply with the precautions after hearing and fully understanding the detailed explanation of the purpose, method, and effects of this study

Exclusion Criteria:

1. Body mass index (BMI) ≥ 35 kg/m2 at screening

2. Hip osteoarthritis or osteoarthritis of another joint that is severe enough to preclude evaluation of knee osteoarthritis at the time of screening

3. Having the following diseases that may affect the efficacy and safety evaluation but not being limited to the following

   • Septic arthritis, rheumatoid arthritis, gout, recurrent pseudogout arthritis, trauma that may damage joint cartilage, congenital abnormalities, calcium deposition disease, diabetes, ochronosis, hemochromatosis, acromegaly, Wilson's disease, primary osteochondrosis, genetic diseases (e.g., hyperkinesis), secondary osteoarthritis caused by collagen gene abnormalities, etc.
   • Sudek's atrophy or severe painful diseases such as Paget's disease

4. Infection or skin disease in the joint area that is unsuitable for injection at the time of screening

5. Active or suspected knee joint infection at the time of screening

6. Complete loss of the Patello-femoral joint space

7. Received the following treatments within 14 days of the screening visit (except those who have passed a 14-day wash-out) or scheduled to be administered during the study period

   • Taking medicines containing ingredients such as glucosamine, chondroitin sulfate, and diacerhein
   • Taking herbal medicines and herbal medicines for osteoarthritis
   • Taking anti-inflammatory painkillers, non-steroidal anti-inflammatory drugs (NSAIDs, prescription/non-prescription drugs), etc. (administration of acetaminophen allowed if passing a 3 day wash-out)
   • Taking oral steroids
   • Hospital physical therapy or oriental medicine treatment (cupping, acupuncture, moxibustion, etc.)

8. Intra-articular injection, such as intra-articular corticosteroid, at the injection site within 6 months from the time of screening

9. Systemic use of steroids within 3 months from the time of screening (including inhalants, however, topical application is permitted only on the upper body)

10. Surgical operations such as knee joint replacement, including arthroscopic surgery, at the administration site within 6 months from the time of screening; or expecting surgery within 6 months

11. Moderate or severe joint effusion by Patella tap test at the screening visit

12. History of hypersensitivity to ingredients of the IP or active control drug

13. Antiplatelet agents (excluding aspirin of 300 mg/day or less), heparin, oral anticoagulants (coumarin anticoagulants, thrombin inhibitors, Factor Xa inhibitors, etc.), and thrombolytics must be used during the study

14. Clinically significant abnormalities in liver function (3 times or more than the upper limit of normal for ALT/AST) or abnormalities in renal function (3 times or more than the upper limit of normal for serum creatinine), or severe liver or renal disease at the discretion of the investigator which is judged to have an impact on the effectiveness and safety evaluation of the study

15. The following clinically significant diseases in the past or present

    • Diagnosis of malignancy within 5 years prior to screening or currently
    • Cardiac disorders (myocardial infarction, coronary artery bypass surgery, arrhythmia, and other serious Cardiac disorders, etc.)
    • Uncontrolled hypertension (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg)
    • Severe endocrine diseases (diabetes insipidus, Cushing's disease, etc.) which is judged to have an impact on the efficacy and safety evaluation of the study

16. Currently pregnant or lactating; or planning to become pregnant/lactating during this study

17. Women of childbearing age who have not undergone sterilization surgery, women less than 1 year after menopause, or men who do not agree to avoid pregnancy or use appropriate contraceptive methods during the study period

18. Planned to participate in another study during the study period or having administered (applied) other investigational product (investigational device) within 3 months prior to the screening visit

19. Difficult to conduct the study as judged by the investigator due to other reasons