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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Combination product: Regen Matrix-PRP-XLHA; Device: Hylan G-F 20; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Corbeil-Essonnes, France
    • Centre Hospitalier Sud-Francilien
  • Créteil, France
    • CHU Henri Mondor APHP
  • La Roche-sur-Yon, France
    • Centre Hospitalier Departemental Vendee
  • Limoges, France
    • CHU Limoges
  • Lyon, France
    • Centre Hospitalier Lyon Sud
  • Montpellier, France, 34295
    • Hopital Lapeyronie
  • Nantes, France
    • CHU Nantes Hôtel - Dieu
  • Narbonne, France
    • CH de Narbonne
  • Paris, France
    • Hôpital Saint-Antoine
  • Paris, France
    • Hopital Lariboisiere
  • Reims, France, 51092
    • Hopital Maison Blanche
  • Toulouse, France, 31100
    • Clinique Medipole Garonne, Radiologie Interventionnelle 45 Rue Gironis
  • DE
    • Dijon, DE, France, 21079
      • Hopital Le Bocage Chru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RegenMatrix-PRP-XLHA; 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; Single intra-articular injection at Day 0
Active Comparator: Hylan G-F 20; 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; Single intra-articular injection at Day 0
Placebo Comparator: Placebo; Patients randomized in this group will receive a single injection of saline solution (0.9% NaCl)	Drug: Placebo; Single intra-articular injection at Day 0

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: RegenLab France SAS
• Investigators: Principal Investigator: Paul Ornetti, MD, Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2023
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: February 3, 2023
• First Posted (Actual): February 14, 2023

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: knee osteoarthritis; platelet-rich plasma; cross-linked hyaluronic acid
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Protective Agents; Viscosupplements; Hylan
• Other Study ID Numbers: 2022-A01514-39

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No