Performance of CCoat Intra-Articular Injections in Mild to Moderate Knee Osteoarthritis: A Prospective, Randomized, Double-Blind, Multi-center Trial

The study aims to evaluate the performance of a single intra-articular injection of CCoat in patients with mild to moderate knee osteoarthritis over 26 weeks. Intra-articular injections are widely used for their localized efficacy and reduced systemic toxicity compared to oral treatments. Current treatments, including corticosteroids and hyaluronic acid, have limitations such as short-term effects and potential cartilage damage [1],[2],[3],[4]. Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) offer promise but require further validation [5],[6],[7]. CCoat, a liposomal boundary lubricant, provides a novel approach by coating cartilage surfaces to reduce wear, offering mechanical protection without altering synovial fluid properties.

CCoat is a new intra-articular (IA) injectable joint lubricant for patients suffering from mild to moderate knee osteoarthritis (OA), developed by Liposphere LTD. CCoat is a liposomal boundary lubricant that coats the cartilage surface and temporarily protects it from further damage and degradation.

The performance and safety of CCoat device over 26 weeks is being evaluated in another multi-center, prospective, placebo controlled, randomized, double- blinded clinical study in 150 patients with mild to moderate OA of the knee (per study protocol # CLD0000616). As this study is ongoing, there is no currently available data related to the performance of the device. With regards to the CCoat's safety, in the interim analysis no safety concerns were raised.

This clinical investigation aims to further confirm the performance of CCoat when used as intended for the treatment of mild to moderate knee osteoarthritis (OA) in a larger patient population group, in comparison to a marketed hyaluronic acid product. This study is critical to further confirm the benefit-risk profile of the CCoat device as a valid therapeutic option for knee OA treatment, which remains a significant unmet medical need.

Inclusion Criteria:

1. Subject has signed and dated the informed consent form (ICF).

2. Age ≥18 years.

3. Participants must have a KOOS Pain subscale score of 25≤75 in the index knee over the last week before screening.

   • Minimum baseline severity: At least two items in the KOOS Pain Subscale must be scored as moderate or worse (score 2-4 on the 0-4 scale).
   • Pain consistency: Subjects must have experienced knee pain on most days in the past month to exclude acute or transient cases.

4. Participants must have a KOOS Symptoms subscale score of 30≤ 75 in the index knee over the last week before screening. Subjects must report at least moderate severity (score ≥2) in at least one of the following:

   • Knee stiffness in the morning
   • Knee stiffness after sitting/resting
   • Swelling in the knee

5. Degenerative changes in the index knee that can be categorized as grade II -III- Kellgren Lawrence based upon standing anterior- posterior and lateral radiographs of the knee.

6. Body Mass Index (BMI) between 18.5 kg/m2 and 38 kg/m2

7. A negative urine pregnancy test female patient with childbearing potential at Visit 1 prior to intra-articular injection of CCoat.

8. If female, the subject must be either postmenopausal, OR permanently surgically sterile OR for women of childbearing potential using at least 2 methods of birth control that are effective from at least 30 days before Visit 1 through visit 26 w (26 weeks post injection).

9. Are willing or able to comply with the procedures required in this protocol.

Exclusion Criteria:

1. Osteoarthritis of the index knee graded 4 according to the Kellgren- Lawrence Grading.
2. History of significant knee trauma or previous surgery of the intended study knee within the last 3 months preceding the screening.
3. KOOS Pain subscale score of ≤25 or >75 in the index knee.
4. Pain in the contra lateral knee: KOOS Pain subscale score of ≤75.
5. Intra-articular injection to the intended study knee within 3 months before screening.
6. Significant instability of the index knee.
7. Malalignment of more than 10 degrees varus OR 10 degrees valgus according to standing X-ray.
8. Intake of chronic pain medications (especially opioid pain relievers) without an option to pause for the period of the study.
9. History of Psoriatic Arthritis, Rheumatoid Arthritis, or any other inflammatory condition associated with arthritis.
10. Wound in the area of the index knee.
11. Any known tumor of the index knee.
12. Any known history of intra-articular or osseous infection of the index knee.
13. Any evidence of active infection anywhere in the body.
14. Any known systemic cartilage and/or bone disorder, such as but not limited to, chondrodysplasia or osteogenesis imperfecta.
15. Active malignancies, excluding BCC.
16. Chemotherapy and/or radiation in the past 12 months.
17. Known history of a severe allergic reactions.
18. Patient who is pregnant or intends to become pregnant during the study.
19. Breastfeeding female patients.
20. History of any significant systemic disease, such as but not limited to: hepatitis and coagulopathies.
21. Immunosuppressives, anti-coagulants.
22. A known substance or alcohol abuse.
23. Participation in other clinical trials within 60 days to before the study or concurrent with the study.
24. Known insulin dependent diabetes mellitus.

Participant, Investigator and sponsor are blinded.