Clinical trial NCT06097988: Study on Knee Osteoarthritis
Official title: A Prospective, Multicenter Clinical Investigation Evaluating the Safety of ABIO3419 in Treating Knee Osteoarthritis: Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Knee Osteoarthritis
Lead sponsor: Symatese
Sponsor class: INDUSTRY
First posted: 2023-10-24
Enrollment: 20
Sex: ALL
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

Brief summary: Osteoarthritis (OA) is a chronic degenerative joint disease characterized macroscopically by progressive damage of articular cartilage, joint space narrowing, subchondral bone remodelling, joint marginal osteophyte formation and synovitis. It is also characterized by a decrease of the concentration and molecular weight of the hyaluronic acid in the synovial fluid which ultimately leads to poor viscoelastic properties of synovial fluid and induction of proinflammatory pathways.

The intra-articular injection of viscosupplementation gel (mainly exogenous hyaluronic acid) represents one of the most used therapeutic strategies to treat osteoarthritis symptoms.

Several studies on knee Osteoarthritis, have shown that one or more weekly injection of viscosupplementation gel significantly relieves articular pain and ameliorates mobility and joint function for at least 6 months and more. Repeated courses of intra-articular injections are an effective and safe treatment for knee osteoarthritis symptoms.

Based on studies conducted on intra-articular viscosupplementation gels, the most common side effects expected are local transient and short-lived adverse events such as pain, swelling and arthralgia in the site of administration, which are fully reversible in the days following the injection. Furthermore, such local effects may occur in a minority of cases and are usually treated conservatively with ice, non-steroidal anti-inflammatory drugs, and relative rest.

Detailed description: The study is a pilot, prospective, multicenter, clinical trial that aims to evaluate the safety and efficacy of ABIO3419 for the treatment of knee osteoarthrosis.

Eligibility criteria: Inclusion Criteria:

1. Voluntarily given informed consent to investigation participation in writing encompassing consent to data recording and verification procedures.
2. Male and female subjects, aged 35 to 85 years (inclusive).
3. Subjects affected by knee osteoarthritis, as defined by American College of Rheumatology (ACR) clinical and radiographic criteria for osteoarthritis of the knee, and meeting the following conditions:

   1. Kellgren-Lawrence Grade 2 to 3 severity osteoarthritis of the knee confirmed by an extension face X-rays shot, supported by flexion face X-rays shot (optional) obtained within 6 months from the screening visit.
   2. Subjects suffering from osteoarthritis symptoms of the target knee for at least 6 months prior to the screening visit.
4. Pain during walking on flat ground in the target knee of at least 40 mm and maximum 80 mm on a 0-100 mm Visual Analogic Scale at the baseline visit (Visit 2).
5. Women of childbearing potential must have a negative urine pregnancy test prior to each injection.
6. Subject who is able to comply with the study requirements, at the Investigator's appreciation.
7. Subject being affiliated to a health social security system

Exclusion Criteria:

1. Pregnant and breastfeeding women
2. Subject with bilateral osteoarthritis of the knees is excluded if one of the following point is present on the non-targeted knee has:

   * a visual analog scale score greater than 30mm (\> 30mm),
   * a Kellgren-Lawrence score is greater than 2 (\>2)
   * a dedicated antalgic consumption.
3. Subject suffering from a severe or progressive disease or any other pathology which, according to the investigator, may interfere with evaluation of the results of the study: diabetes, autoimmune pathology, cardiac pathologies, hepatic deficiency, epilepsy, porphyria, rheumatoid arthritis or other systemic inflammatory process.
4. Subject who has a known history of severe multiple allergies, angioedema or anaphylactic shock according to the investigator opinion.
5. Subject with a known allergy or hypersensitivity to Hyaluronic Acid or bovine collagen.
6. Subject with a past history of severe streptococcal disease or an active streptococcus infection according to the investigator opinion.
7. Subject with a disorder that may impact wound healing such as connective tissue or immunosuppressive disorder.
8. Subject having received chemotherapy agents, immunosuppressive medications within the past 3 months.
9. Subject with bleeding disorders or subject received medication (anti-platelet agents and anticoagulant) that will likely increase the risk of bleeding within the past 24 hours before injections.
10. Subjects having received:

    1. Intra-articular knee corticosteroids within 60 days prior to the baseline visit.
    2. Chondroitinsulphate, glucosamine sulphate, diacereine, bisphosphonates or matrix metalloproteinase inhibitors within 30 days prior to the baseline visit.
    3. Viscosupplementation of the target knee within 6 months prior to the baseline visit.
    4. Any kind of antalgic and Non-steroidal anti-inflammatory drugs in the 24 hours prior to the baseline visit (V2) and before each visit.
11. Subjects with a Kellgren-Lawrence grade 4 femora-patellar osteoarthritis or subjects with a femora-patellar osteoarthritis Kellgren-Lawrence grade higher than the femora-tibial one.
12. Subjects with coxarthrosis.
13. Subjects having had any previous surgery in the target knee within 6 months prior to the screening visit, or any planned surgery in the target knee throughout the duration of the investigation.
14. Subjects who have had arthroplasty at the target knee at any time.
15. Subjects having had diagnostic or surgical knee arthroscopy, or knee lavage in the target knee in the 6 months prior to the screening visit.
16. Subjects that are candidate for knee replacement within next 6 months.
17. Subjects with body mass index \> 35 kg/m2.
18. Subjects with large intra-articular effusion of the target knee, venous or lymphatic stasis, inflammatory flare-up with various symptoms, local inflammation.
19. Subjects with history of septic osteoarthritis of any joint
20. Subjects with significant pain outside the target knee, including significant hip or back pain and with fibromyalgia.
21. Subjects with clinically significant valgus/varus deformities, ligamentous laxity, or meniscal instability as assessed by the Investigator.
22. Subjects with other musculoskeletal condition affecting the target knee that would impair assessment of the effectiveness in the target knee (e.g. Paget's disease of bone).
23. Subjects with a current malignancy or having treatment for a malignancy, except non-melanoma skin cancer.
24. Subjects with drug or alcohol abuse
25. Subject who is deprived of their freedom by administrative or legal decision.
26. Subject living in a social or sanitary establishment.
27. Subject being in an exclusion period for a previous study or with a current or recent (\<3 months) participation in another investigational study involving a drug or combined device with drug.
28. Other condition preventing the subject to participate the study in the Investigator's opinion: subject deemed unreliable or incapable of understanding and complying with the study assessment or unrealistic expectations of treatment results.

Primary outcomes:
measure: Incidence of adverse device effects related to ABIO34199 treatment [tolerability] at 3 months
timeFrame: Month 3 after the last injection
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety]
timeFrame: Immediately after first injection, before and immediately after the injections at 1 week and 2 weeks, then at 2 weeks, 1 month, 3 months and 6 months after the last injection
measure: Evaluation of the pain of the treated knee when walking on a flat ground.
timeFrame: Baseline (before initial injection), 1 week and 2 weeks after the first injection (before 2nd and 3rd injections) then 2 weeks, 1 month and 3 months after the last injection.
measure: Device related complication rates
timeFrame: Immediately after first injection, before and immediately after the injections at 1 week and 2 weeks, then at 2 weeks, 1 month, 3 months and 6 months after the last injection
measure: General health status of the treated knee
timeFrame: Baseline (before initial injection), 1 week and 2 weeks after the first injection (before 2nd and 3rd injections) then 2 weeks, 1 month and 3 months after the last injection.
measure: Concomitant analgesic consumption
timeFrame: 1 week before the first injection, 1 week and 2 weeks after the first injection then 2 weeks, 1 month and 3 months after the last injection.
measure: Implant card readability
timeFrame: Day 0 (after first injection)
measure: Investigator Global satisfaction
timeFrame: Week 2 after first injection
measure: Investigator Global satisfaction
timeFrame: Month 6
measure: Patient Global satisfaction
timeFrame: month 6
Other outcomes:
Locations:
city: Riga
country: Latvia
facility: Knohenfelds
city: Riga
country: Latvia
facility: KRASTINS
Study officials:
affiliation: Veselibas Centrs ZIN
name: Kristaps KNOHENFELDS
role: PRINCIPAL_INVESTIGATOR
affiliation: Private Office Centrs
name: Kalvis KRASTINS
role: PRINCIPAL_INVESTIGATOR
References: