The Efficacy and Safety Study of 2107 Injection in Subjects With Mild to Moderate Knee Osteoarthritis

N/ANot Yet RecruitingNCT07746843

BioRegen Biomedical (Changzhou) Co., Ltd286 enrolled

Overview

This will be a 26-week, prospective, international, multi-center, randomized, active-controlled, double-blinded (to subject and Investigator) study in subjects with mild to moderate OA in the knees to assess safety and efficacy of 2107 Injection following a single intra-articular injection as compared to DUROLANE® (the active comparator). A total of 286 subjects from approximately 15 sites and at least three (3) countries will be enrolled and randomized at a 1:1 ratio into the 2107 Injection arm or DUROLANE® arm. One (1) target knee of each subject (only one \[1\] knee to be treated) will receive a single intra-articular dose of 3 mL of 2107 Injection (16 mg/mL HA, i.e. 48 mg per dose) or 3 mL of DUROLANE® (20 mg/mL HA, i.e. 60 mg per dose). Subjects will be followed for 26 weeks after the intra-articular injection for safety and efficacy assessments. The study will consist of six (6) visits (see Table 1. Schedule of Assessments). Subjects who withdraw from the study will have an early termination visit. The primary efficacy endpoint will be the mean change in the Western Ontario and McMaster Universities (WOMAC) Pain sub-score on 100-mm Visual Analog Scale (VAS) from baseline to 13 weeks after intra-articular injection. The secondary efficacy endpoints include the changes in WOMAC sub-score and total score, PGA/IGA, the percentage of subjects taking rescue medication, the level of swelling and tenderness of the target knee and the Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) responder rate. The safety endpoint includes systemic and local safety profile.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

286

Conditions

Eligibility

Sex: ALLMin age: 40 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 1)Male or female outpatients 40-80 (inclusive) years of age. 2) Documented diagnosis of knee OA confirmed according to the American College of Rheumatology (ACR) criteria7 with symptoms for at least six (6) months. 3\) Diagnosed with mild to moderate OA based on radiographs (Kellgren-Lawrence scale Grade II-III) taken within 12 months prior to entering the study. The rating of the alternative knee (Kellgren-Lawrence scale) should be no higher than that of the target knee. 4\) Subjects could have OA in both knees, but the target knee for treatment should have an average total pain score of 40-80 mm (of the five \[5\] pain questions) and the walking pain question score of 40 60 mm on WOMAC Pain sub-score using a 100-mm VAS. The pain scores of the alternative knee should not be higher than that of the target knee (a higher-pain-score side of knee is defined as the target knee even if it has a lower Kellgren-Lawrence scale Grade). 5\) Constant (daily) pain symptoms despite conservative care (e.g., physical therapy, analgesics) \> two (2) weeks. 6\) Agree to discontinue all analgesic therapies for at least 72 hours or four (4) to five (5) half-lives of the analgesics, whichever is longer. 7\) Subject voluntarily agrees to sign the informed consent form (ICF). 8) Subject is self-conscious and able to read and write. Exclusion Criteria: * Subjects who meet any of the following criteria are not eligible for this clinical investigation: 1. Diagnosed with rheumatoid arthritis, another inflammatory metabolic arthritis (gout), or any other diseases that affects joints (e.g., rheumatoid arthritis, metastatic bone diseases, psoriatic arthritis, gouty arthritis, symptomatic cartilaginous calcification, osteonecrosis or active infections). 2. History of hypersensitivity to HA. 3. Infection in the target knee, or skin ulceration or infection of the injection site, or chronic skin diseases that may affect manipulation of injection and/or assessment of the injection site, or localized skin disease at the site to be injected. 4. History of clinically apparent tense effusion of the target knee. 5. Chronic pain anywhere requiring analgesic therapy that would confound the measurement of pain in the target knee. 6. Received a corticosteroid injection within 12 weeks or oral corticosteroids within six (6) weeks prior to screening. 7. Any intra-articular injection(s) within 36 weeks prior to screening or glucosamine-chondroitin within the past three (3) months prior to baseline. 8. Took any of the following medications within seven (7) days prior to screening. Unless noted, these medications are prohibited in oral, injectable and suppository forms, but they can be used in inhaled, nasal or ophthalmic formulations. Topical administration is permitted except for the lower extremity of the ipsilateral side of the target knee: * NSAIDs * Medicines for neuropathic pain (pregabalin, gabapentin) * Topical capsaicins * Duloxetine (serotonin-norepinephrin reuptake inhibitors) * Local anesthesia to either knee (local anesthesia to target knee during injection procedure is permitted) * Anticonvulsant drugs, any type of medicine with analgesic properties * Opioids * Anti-depressants, anti-anxiety, anti-psychotic, mood stabilizers and sleeping drugs 9. Documented history of serious injuries to the target knee restricting ambulation. 10. Therapeutic arthroscopy and/or other surgical procedures within 12 months prior to screening (diagnostic arthroscopy ≥60 days prior to screening is allowed). 11. Had a knee replacement. 12. History of chondrocalcinosis, depression, or a sleep disorder. 13. Had a body mass index (BMI) ≥39 kg/m2. 14. Any other condition that could affect the outcome assessment. 15. Clinically apparent tense effusion of the target knee on examination determined by either a positive bulge sign or positive ballottement of the patella (patellar tap). 16. Unable to walk (walking aid is allowed to continue to use during the trial period, if its usage began ≥12 weeks prior to the enrollment check-up). 17. Coxitis. 18. Metastatic malignant tumor or received treatments for a metastatic malignant tumor within five (5) years prior to the enrollment check up, except for skin cancers other than melanoma. 19. Valgus/varus deformities, ligament laxities, or meniscus instabilities; 20. Combined chronic pain diseases with VAS ≥40 mm, peripheral or central neural diseases that possibly alter sensations of the target knee areas, including but not limited to back pain, hip pain, disk herniation, neuralgia, diabetic neuropathy, post-stroke pain or fibromyalgia. 21. Lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) that require the usages of systematic or inhaled corticosteroids during the trial period. 22. Venostasis or lymphostasis of the lower extremities. 23. Lymph or peripheral vascular diseases. 24. Currently receiving oral or parenteral anticoagulation treatments, or receiving aspirin antiplatelet aggregation treatments; a low dose treatment of acetylsalicylic acid (Aspirin) will be considered acceptable at the discretion of the Principal Investigator (PI). 25. Severe diseases such as myocardial infarction, congestive heart failure, unstable angina, cerebrovascular diseases, and severe renal insufficiency. 26. Severe hepatic disease or history of severe hepatic disease. 27. Positive for human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus. Patients with serologic evidence of hepatitis B vaccination (hepatitis B surface antibody without the presence of hepatitis B surface antigen) will be allowed to participate. 28. Coagulation dysfunction, such as hemophilia, Von Willebrand disease, antiphospholipid syndrome (APS). Subjects under anticoagulant therapies will have to interrupt their treatment 48 hours before the injection, and start their usual anticoagulant treatment again only 48 hours after the injection. 29. Positive pregnancy test, lactating, planning to get pregnant, unwilling or unable to use highly effective contraceptive measures during the study. 30. Any other conditions that lead the Investigators to consider the subject as ineligible to enroll, such as alcohol intake, drug usage, psychiatric disorder, etc. 31. Any acute or chronic illness/condition or evidence of an unstable clinical condition that in the Investigator's judgement will substantially increase the risk to the subject if they participate in the study. 32. Subject has an intellectual disability.

Outcomes

Primary Outcomes

Mean change in WOMAC Pain sub-score (100-mm VAS) from baseline to Week 13

The primary endpoint will be the mean change in the Western Ontario and McMaster Universities (WOMAC) Pain sub-score on 100-mm Visual Analog Scale (VAS) from baseline to 13 weeks after intra-articular injection.

Time frame: Baseline to Week 13

Secondary Outcomes

Change in WOMAC total, Physical Function and Stiffness sub-scores (100-mm VAS)

Changes in the WOMAC total score, WOMAC Physical Function and WOMAC Stiffness sub-scores on 100-mm VAS from baseline to 13 and 26 weeks post-injection.

Time frame: Baseline to Week 13 and Week 26 post injection

Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale (100-mm Visual Analog Scale)

Changes from baseline to each study visit (through 26 weeks post single intra-articular injection) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale scored using a 100-mm Visual Analog Scale (VAS). This scale ranges from a minimum value of 0 mm to a maximum value of 100 mm; higher scores indicate worse knee pain symptoms, and lower scores indicate less pain.

Time frame: Baseline through 26 weeks post injection

Change in Patient's Global Assessment (PGA) Scale (100-mm Visual Analog Scale)

Changes from baseline to Week 13 and Week 26 post-injection in scores of the Patient's Global Assessment Scale measured via a 100-mm Visual Analog Scale (VAS). The scale ranges from a minimum value of 0 mm to a maximum value of 100 mm; higher scores represent worse overall knee osteoarthritis condition, while lower scores represent milder symptoms and better clinical status.

Time frame: Baseline through Week 13 and Week 26 post injection

Percentage of subjects using rescue medication

The percentage of subjects taking rescue medication at each visit post-injection.

Time frame: All post-injection study visits up to 26 weeks

Knee swelling and tenderness (4-point scale)

The level of swelling and tenderness of the target knee using a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) at each visit.

Time frame: All post-injection study visits up to 26 weeks

Change in Investigator's Global Assessment (IGA) Scale (100-mm Visual Analog Scale)

Investigator's Global Assessment Scale scores measured using a 100-mm Visual Analog Scale (VAS), assessed from baseline to Week 13 and Week 26 post-injection. This scale has a minimum value of 0 mm and a maximum value of 100 mm; higher scores indicate a more severe overall knee osteoarthritis condition (worse outcome), and lower scores indicate milder disease symptoms (better outcome).

Time frame: Baseline through Week 13 and Week 26 post injection

OMERACT-OARSI responder rate

The OMERACT-OARSI responder rate at 13 and 26 weeks post-injection. An OMERACT-OARSI positive response is defined as WOMAC Pain or Physical Function sub-score improvement of ≥50% and ≥20 points over baseline or ≥20% improvement.

Time frame: Week 13 and Week 26 post injection