Safety of Use of Pandora for Patients Suffering From Gonarthrosis

Study Overview
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Brief Summary
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The knee osteoarthritis is a frequent degenerative condition that mainly affects subjects over 60, population often weakened by numerous comorbidities and concomitant treatments, justifying the development of new therapies. The viscosupplementation is a symptomatic treatment for knee osteoarthritis ; the objective of this intra-articular injection of hyaluronic acid is to reduce knee pain and improve mobility. In practice, there are two protocols to administer viscosupplementation : in a single injection or in three injections performed weekly. The present clinical investigation has the objective to evaluate the safety of use of Pandora in a single injection or in three injections performed weekly.

Detailed Description
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This clinical investigation is a multicenter, prospective, open study of a class III Medical Device. This study is designed to evaluate the safety of use of Pandora in its two forms : in a single injection or in three injections. A descriptive analysis will be carried out to characterize the demographic data, the history of the disease and its treatments, the clinical and radiological data of the patients at inclusion. The security of use of Pandora will be demonstrated by describing the proportion of patients with at least one adverse event attributable to the treatment, occurring during the week following each injection. In total, 20 participants will be enrolled across two study centers in France, 10 participants in each centers. The total duration of subjects participation is 6 months ; overall study duration including the enrollment period is expected to take approximately 9 months.

Official Title
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Prospective, Multicenter, Open Study Evaluating the Short-term Safety of Use of Pandora Administered in the Form of 1 Intra-articular Injection of Happyone or 3 Intra-articular Injections of Happysoft in Patients Suffering From Gonarthrosis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: Intra-articular single injection
* Device: Intra-articular three injections


Participation Criteria
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Eligibility Criteria
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Twenty patients having a gonarthrosis asserted radiologically and justifying according to the opinion of the rheumatologist a viscosupplementation. Inclusion Criteria: Patient aged between 35 and 85 years. Body mass index (BMI) < 30 kg.m^2. Medial or lateral femoro-tibial knee osteoarthritis, diagnosed according to the American College of Rheumatology criteria, radiological stage 2 and 3 according to the Kellgren-Lawrence criteria modified by Felson on an X-ray, of the knee in extension, less than 12 months old. Knee osteoarthritis responsible for walking pain in the target knee, assessed between 4 and 8 inclusive on an 11 points numerical scale (0 = none to 10 = extreme). Ambulatory patient able to walk 50 meters without a cane, crutch or walker. Patient able to read, understand, sign and date the patient information sheet. Patient agreeing to follow-up study visits. Patient affiliated to the health social security system. Patient requiring viscosupplementation according to the investigator. Exclusion Criteria: Patient presenting knee osteoarthritis without impingement joint space narrowing of the femoro-tibial compartment (modified Kellgren stage 0-1) or with complete impingement joint space narrowing on the knee weight-bearing radiograph in extension (modified Kellgren stage 4). Walking pain in the target knee, rated less than 4 or more than 8 on an 11-point numerical scale (0 = none to 10 = extreme). Patient with a flare of osteoarthritis of the target or contralateral knee attested by KOFUS criteria ≥ 7. Patient who received viscosupplementation or Platelet Rich Plasma (PRP) injection in the 6 months prior to inclusion. Patient who received an intra-articular injection of corticosteroids in the target knee in the 2 months prior to inclusion. Patients with a skin condition or a wound next to or near the injection site. Patients refusing to discontinue treatment with NSAIDs or cox-2 inhibitors during the follow-up period. Patient receiving treatment with level III analgesics (strong opioids). Patients receiving treatment with diacerhein, avocado and soy unsaponifiables, glucosamine or chondroitin initiated less than 2 months prior to inclusion. Patient with hypersensitivity to hyaluronic acid or tranexamic acid. Patient with a history of seizures. Patient who had arthroscopy of the target knee or major trauma to the target knee during the 3 months preceding inclusion. Patient scheduled to undergo surgery, for any cause, of the target knee or other joint of the lower limbs, planned within 6 months of inclusion, likely to interfere with follow-up or evaluation of the patient in the study. Patient with Fibromyalgia. Patient with an active neurological or vascular musculoskeletal disorder (such as rheumatoid arthritis, lupus, psoriatic arthritis, spondyloarthritis or any other autoimmune disease, Paget's disease, gout, coxopathy, tendinopathy of the lower limb, sciatic or crural radiculalgia) that could interfere with the measurement of the effectiveness of the treatment of the knee evaluated. Patient with hemostasis disorders, venous or lymphatic stenosis of the lower limbs, history of thromboembolic disease - phlebitis or pulmonary embolism - or a high risk of thromboembolism. Patients with an evolving general cardiac, digestive, endocrine, haematological or broncho-pulmonary condition which, in the opinion of the investigator, would be likely to disrupt regular monitoring and/or interfere with the measurement of treatment efficacy . Breastfeeding patient, pregnant or wishing to be during the 6 months of the study. Patient unable to give personal consent. Patient with renal insufficiency.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, Multi-center, Open Clinical Investigation. Two facilities are participating ; each facility will be in charge and perform a type of viscosupplementation procedure : single injection or three injections. Subjects will received one or the other viscosupplementation depending of the facility in which they will be included.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medical Device : Happyone<br>Hyaluronic acid associated with tranexamic acid ; 4.8 ml will be injected in one time | Device: Intra-articular single injection<br>* Both groups will receive their first injection after a selection visit ; first injection will be planned between 7 days to 30 days after to confirm the enrollment. The injection will be performed at Day 1.<br>|
| Experimental: Medical Device : Happysoft<br>Hyaluronic acid associated with tranexamic acid ; 2.2 ml will be injected in three times (one injection per week) | Device: Intra-articular three injections<br>* Both groups will receive their first injection after a selection visit ; first injection will be planned between 7 days to 30 days after to confirm the enrollment. The injections will be performed at Days 1, 8 and 15.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse event attributable to the investigational Medical Device during the week following each injection. | Adverse events will be collected at : Day 8 for Happyone arm (single injection) ; Days 8, 15 and 22 for Happysoft arm (three injections). | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events during the month following the first injection for immediate and delayed local tolerance evaluation. | All adverse events will be collected at : Days 3, 8, 22 and 29 for Happyone arm (single injection) ; Days 3, 8, 10, 15, 17, 22 and 29 for Happysoft arm (three injections). Number of adverse events occurring beyond the week following each injection from Day 1 to D29. | 1 month | 
| Patient self-assesment of the overall tolerance of the treatment based on a 5-point scale, from Very bad to Very good. | This questionnaire will be completed at : Days 3, 8, 22 and 29 for Happyone arm (single injection) ; Days 3, 8, 10, 15, 17, 22 and 29 for Happysoft arm (three injections). | 1 month | 
| Variation over time of the WOMAC score, between time of injection and end point, and the WOMAC subscores A (pain) and C (function). The WOMAC-Questionnaire is based on a 11 points scale, from 0 = None to 10 = Extreme. | This questionnaire will be completed at : Day 1, Day 8, Month 1, Month 3 and Month 6 for Happyone arm (single injection) ; Day 1, Day 8, Day 15, Month 1, Month 3 and Month 6 for Happysoft arm (three injections). | 6 months | 
| Patient self-assesment of the effectiveness of the treatment based on a 11 points numeric scale, from 0 = None to 10 = Total. | This questionnaire will be completed at Months 1, 3 and 6 for both groups. | 6 months |