Combination of PRP and XLHA Prepared With RegenMatrix Medical Device To Treat Moderate to Severe Knee Osteoarthritis

Study Overview
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Brief Summary
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In this clinical trial the investigator assess the safety and efficacy of a single injection of a combination of cross-linked hyaluronic acid (HA) with autologous platelet-rich plasma (PRP) obtained with the RegenMatrix medical device to improve symptoms of moderate to severe knee osteoarthitis (grade III-IV Kellgren-Lawrence).

Detailed Description
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In this multicenter, randomized, double-blind, three-arm study, the investigator propose to evaluate the safety and efficacy at Day0, Month1, Month3 and Month6 of a single intra-articular injection of a combination RM-PRP-XLHA (experimental treatment: combination of cross-linked HA and PRP obtained with the RegenMatrix medical device) against Hylan G-F 20 (reference treatment) and placebo for the treatment of moderate to severe knee osteoarthritis. The symptomatic benefit will be evaluated in terms of pain reduction and improvement of patient's quality of life. The functional benefit of the treatment will also be evaluated, on a reduced number of participants, by a gait analysis, performed only in the coordinating centre. The medical device RegenMatrix is an adaptation of the medical device Cellular Matrix (certified since 2013,CE2797). It differs from the latter only for by presence of cross-linked HA instead of linear HA, and is therefore particularly suitable for the treatment of moderate to severe knee osteoarthritis.

Official Title
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Multicenter, Randomized Double-blind Study to Compare the Safety and Performance of a Combination of A-PRP and XLHA Prepared With the RegenMatrix Medical Device, to Hylan G-F 20 XLHA and Placebo to Treat Moderate/Severe Knee Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Combination Product: Regen Matrix-PRP-XLHA
* Device: Hylan G-F 20
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Tibiofemoral knee osteoarthrosis according to ACR criteria Tibiofemoral knee osteoarthrosis grade 3-4 according to the Kellgren & Lawrence grading scale, as defined on knee radiographs (less than 3 months old: face view, schuss view, profile and patellar axial view at 30°) Symptomatic knee osteoarthrosis as evidenced by pain on walking (WOMAC A1 assessed in the last 24 hours on a scale of 0 to 100 mm: 50 ≤ DM 90 or reduced joint function (WOMAC C total score assessed or within the previous 24 hours based on a scale of 0-100-mm: 50 ≤ WOMAC C ≤ 90) Patient able to understand the requirements of the trial and who has signed a free and informed consent prior to study entry Patient able to read and understand the written instructions Patient able to complete the self-assessment questionnaires Exclusion Criteria: Tibiofemoral knee osteoarthrosis grade I or II according to the Kellgren and Lawrence grading scale Knee surgery planned in the next 6 months Patient affected by autoimmune disease (rheumatoid arthritis, lupus, Hashimoto's disease and Bechterew's syndrome) Chronic inflammatory rheumatism other than arthritis (polyarthrosis, etc.) Patient affected by a knee infection in the past 6 months Clinical signs of local knee inflammation (redness or warmth of the knee joint) Last PRP or PRP/HA injection received in the last year Last viscosupplementation received in the past 6 months Last corticosteroid injection received in the past 3 months Use of gluco-corticosteroids (except inhaled) and level III analgesics in the last 3 months and non-steroidal anti-inflammatory drug in the last 2 weeks Treatment with AAAL initiated within the last 6 months History of allergy to hyaluronic acid Hematologic or clotting disorders (thrombocytopenia) or blood coagulation (deficit-blood dyscrasia) Patients with coagulation times outside the reference values Anemia (HGB<10 g/dl) Venous or lymphatic stasis in the corresponding limb Malignant diseases (especially bone or haematological) Patients with serious, no-stabilized pathologies (cardiovascular disease, active peptic ulcer, digestive hemorrhage) Acute infection Patients with cancer or with an immuno-deprassant treatment ongoing Participation in another clinical trial for osteoarthritis of the knee in the last year Participation in another clinical trial, ongoing or completed within the last 3 months Patient unable to comply with the constraints of the protocol, in particular a patient whose mental state does not allow him/her to patient's mental state does not allow him/her to understand the nature, objectives and possible consequences of the study Pregnant or breastfeeding women or women who expect to become pregnant during the study Any other reason which may interfere with the proper conduct of the study, in the investigator's opinion

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RegenMatrix-PRP-XLHA<br>Patients randomized in this group will receive a single injection of a combination of platelet-rich plasma plus cross-linked hyaluronic acid, prepared with the medical device RegenMatrix. | Combination Product: Regen Matrix-PRP-XLHA<br>* Single intra-articular injection at Day 0<br>|
| Active Comparator: Hylan G-F 20<br>Patients randomized in this group will receive a single injection of cross-linked hyaluronic acid Hylan G-F 20 (Synvisc-One®). | Device: Hylan G-F 20<br>* Single intra-articular injection at Day 0<br>|
| Placebo Comparator: Placebo<br>Patients randomized in this group will receive a single injection of saline solution (0.9% NaCl) | Drug: Placebo<br>* Single intra-articular injection at Day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation in the osteoarthritis related pain | It will be assessed by the mean difference in the WOMAC A score on a 100-mm VAS overtime | 6 months (Day 0 - Month 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation in the overall osteoarthritis related pain | It will be assessed by the mean difference in the WOMAC A score on a 100-mm VAS overtime | M1 and M3 (Day 0-Month 1; Day 0 - Month 3) | 
| Variation of joint stiffness after the first awakening and later in the day | It will be assessed by the mean difference in the WOMAC B score overtime | Month 1, Month 3 and Month 6 (Day 0-Month 1; Day 0-Month 3; Day 0-Month 6) | 
| Variation of joint function during daily activity | It will be assessed by the mean difference in the WOMAC C score overtime | Month 1, Month 3 and Month 6 (Day 0-Month 1; Day 0-Month 3; Day 0-Month 6) | 
| Variation in the osteoarthritis related symptoms | It will be assessed by the mean difference in the total WOMAC score Month 1, Month 3 and M6 (D0-M1; D0-M3; D0-M6) | Month 1, Month 3 and Month 6 (Day 0-Month 1; Day 0-Month 3; Day 0-Month 6) | 
| Variation of patient's quality of life | It will be assessed by the SF-12 questionnaire | Month 1, Month 3 and Month 6 (Day 0-Month 1; Day 0-Month 3; Day 0-Month 6) | 
| Pain, function, patient's general assessment | It will be assessed by the% of OMERACT-OARSI responders | Month 1, Month 3 and Month 6 (Day 0-Month 1; Day 0-Month 3; Day 0-Month 6) | 
| Assessment of the minimal meaningful change according to the patient's perception | The Minimal Clinically Important Improvement (MCII) will be assessed on the basis of the answers to the WOMAC questionnaire. | Month 1, Month 3 and Month 6 (Day 0-Month 1; Day 0-Month 3; Day 0-Month 6) | 
| Assessment of the highest level of symptom beyond which patients consider themselves well. | The Patient Acceptable Symptom State (PASS) will be assessed on the basis of the answers to the WOMAC questionnaire. | Month 1, Month 3 and Month 6 (D0-Month 1; Day 0-Month 3; Day 0-Month 6) | 
| Rescue medication | Consumption of level 1 and 2 painkillers, NSAIDs and corticosteroids | Month 1, Month 3 and Month 6 (Day 0-Month 1; Day 0-Month 3; Day 0-Month 6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platelet-rich plasma, cross-linked hyaluronic acid, knee osteoarthritis