Clinical Trial to Assess the Safety and Efficacy of Intra-articular Injection Collagen Versus Hyaluronic Acid on Knee Osteoarthritis

A Double Blind, Randomized Post Marketing Clinical Trial to Assess the Safety and Efficacy of Intra-articular Injection Collagen Versus Hyaluronic Acid on Knee Osteoarthritis

This study was designed to assess the efficacy for pain relief, functional improvement, and safety of intra-articular collagen injections compared to hyaluronic acid injections for knee osteoarthritis.

This is a double-blind study involving 100 participants. After receiving an explanation of the study and voluntarily providing written informed consent, subjects underwent a screening process to confirm eligibility. Eligible subjects were randomly assigned to receive an intra-articular injection of either collagen or hyaluronic acid. To maintain the double-blind design, the intra-articular injection was administered by a separate unblinded injector. During the study period, subjects were required to follow the investigator's instructions. According to the study protocol, subjects participated in the study for 12 months from enrollment. A total of six hospital visits were conducted, including a screening visit, an enrollment/injection visit, visits at 4 and 12 weeks after injection, and follow-up visits at 24 and 52 weeks. At each visit, efficacy was evaluated according to the clinical trial protocol through questionnaire assessments and blood tests, and safety was assessed by monitoring adverse events.

Inclusion Criteria:

1. Adults aged 19 years or older
2. Patients with knee pain due to osteoarthritis (OA)
3. Patients with Kellgren-Lawrence grade 3 or less
4. Patients with a 100 mm VAS pain level of 40 mm or greater
5. Patients without clinically significant clinical pathology test results during the screening period
6. Patients who confirmed accurate prescription records for medications taken within at least one week before the study and agree to maintain the same dosage of concomitant medications as before the injection if such medications are continuously administered during the study period
7. If taking concomitant medications, patients who have been on stable medication for approximately two weeks before participating in the study, considering the duration of drug maintenance in the body (stability must be confirmed one week before screening and reconfirmed at the time of registration when the injection is applied to ensure two weeks of stable medication use)
8. Rescue analgesic medications administered within one week of intra-articular injection are allowed (given to the subject after injection), provided that if additional analgesics are required due to increased pain at the observation site, patients should agree not to use more than 5 consecutive days or 10 days per month, and to stop taking analgesics at least 2 days before the next visit.
9. Patients who agree to undergo only non-drug therapies (physical therapy, osteopathy, chiropractic care) as allowed by a clinician (excluding acupuncture)
10. Patients who agree to have the injection administered to the more painful knee if both knees are affected (intra-articular injections in the contralateral knee are prohibited)
11. Patients or their legal representatives who consent to participate in the study and sign the written informed consent form

Exclusion Criteria:

1. Patients with ongoing or past autoimmune diseases, either personally or in their family
2. Patients with a history of anaphylactic reactions
3. Patients with hypersensitivity to implants
4. Patients with hypersensitivity to porcine protein
5. Patients with a Kellgren-Lawrence grade of 4
6. Patients with severe effusion
7. Patients who had a serious injury or received an injection in the affected knee that may interfere with evaluation within 6 months prior to screening
8. Patients with inflammatory arthritis, such as rheumatoid arthritis, lupus arthritis, or psoriatic arthritis (except when deemed eligible for collagen administration by the clinician)
9. Patients with gout or pseudogout diagnosed within 6 months prior to screening (except when deemed eligible for collagen administration by the clinician)
10. Patients with a history of radiation or chemotherapy within the past 2 years (except when deemed eligible for collagen administration by the clinician)
11. Diabetic patients (except those who maintain normal blood sugar levels, have no complications related to diabetes, and are deemed eligible for collagen administration by the clinician)
12. Patients with infections receiving treatment with antibiotics or antimicrobials that require hospitalization (except when deemed eligible for collagen administration by the clinician)
13. Patients receiving adrenocortical hormone therapy (except when deemed eligible for collagen administration by the clinician)
14. Patients with heart, liver, or kidney diseases (except those maintaining normal test results or deemed clinically insignificant by the clinician, in which case collagen administration is allowed; hypertension excluded)
15. Patients with viral infections (except those maintaining normal test results or deemed clinically insignificant by the clinician, in which case collagen administration is allowed)
16. Patients with any clinically significant medical condition that may affect the completion of the study
17. Patients who are pregnant, breastfeeding, or planning to become pregnant
18. Patients with mental illness or others deemed inappropriate for the study by the study staff
19. Patients scheduled for surgery during the study period