Evaluation of the Evolution of Biological and Imaging Markers of Bone and Cartilage Degradation in Patients With Knee Osteoarthritis Receiving Intra-articular Injections of a Hyaluronan Derivative HYMOVIS® (MOKHA)

This pilot study MOKHA is aimed to evaluate the beneficial effect of HYMOVIS® on cartilage of patients suffering of knee osteoarthritis as revealed by using scientifically sound, objective measurements of biological and MRI-based imaging markers.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Device: HYMOVIS

Detailed Description

This study is a post-marketing, open-label, prospective and multicentric pilot study in 50 patients suffering from knee OA. Investigators will be rheumatologists or articular disease specialists from public or academic hospitals located in Belgium and France. In each investigating center, the same injector will perform all the VS.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1020
    • Service de Rhumatologie, CHU Brugmann
  • Liège, Belgium, 4000
    • CHR Citadelle de Liège
  • Liège, Belgium, 4000
    • Service de Rhumatologie CHU Liège
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • Service de Rhumatologie CHU Dinant-Godinne (Site Godinne)
• France
  • Lyon, France, 69003
    • Hopital Edouard Herriot (Lyon)
  • Paris, France, 75010
    • Service de rhumatologie,RDC Hôpital Lariboisière
  • Trévenans, France, 10499
    • Centre Hospitalier Nord Franche-Comté
  • Thionville Cedex
    • Thionville, Thionville Cedex, France, 60327 57126
      • Service de Rhumatologie CHR Metz Thionville Hôpital Bel Air

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female between the age of 40 and 80 with BMI ≤ 40

• Monolateral (unless contralateral knee is grade I and asymptomatic) femorotibial knee OA associated or not with femoropatellar knee OA

  • Responding to clinical and radiological criteria of the American College of Rheumatology (ACR) (Appendix 1)
  • Symptomatic for more than 6 months in the most painful knee
  • Radiological Kellgren & Lawrence (K&L) II or III in radiographs from less than 12 months (Appendix 2)
• Mean knee pain score at rest over the last 24 hours evaluated on VAS (0-100) ≥ 40 (Appendix 3) with a washout period for Paracetamol and oral NSAIDs depending on the half-life of the drug (Appendix 4). The most painful knee is considered.
• Able to follow the instructions of the study
• Having signed an ICF

Exclusion Criteria:

Related to the OA pathology

• Bilateral (except asymptomatic and grade I) OA of the knee
• Radiological K&L grade I or IV (Appendix 2)
• Chondromatosis or villonodular synovitis of the knee
• Recent trauma (< 1 month) of the knee responsible of the symptomatic knee
• Acute inflammatory OA (KOFUS (Knee Osteoarthritis Flare Up Scale) score ≥ 7, Appendix 5)
• Articular disease resulting from articular dysplasia, aseptic osteonecrosis, acromegaly, Paget's disease, hemophilia, hemochromatosis….
• Inflammatory disease i.e. rheumatoid arthritis, gout, infectious arthritis, acute calcium pyrophosphate arthritis
• Pathologies interfering with the evaluation of OA (radiculalgia in the lower limbs, arteritis…..)
• Presence of another joint (other than the target knee) affected by OA (confirmed in radiographs and symptomatic)

Related to treatments

• Corticosteroids injection in the target knee in the last month before first injection
• Hyaluronan injection in the target knee in the last 6 months before first injection
• Arthroscopy and surgery in the target knee in the last 6 months before first injection
• Oral corticotherapy ≥ 5mg/day (in Prednisone equivalent) in the last 3 months before first injection
• OA treatments based on curcuma extract (e.g. FLEXOFYTOL) in the last 3 months before first injection
• Change in the dosage of SYSAD i.e. chondroitin, glucosamine, diacerein or avocado-soy unsaponifiables in the last 3 months before first injection
• Paracetamol and oral NSAIDs before inclusion and follow-up visits (washout period depending on the half-life of the drug, Appendix 4).
• Osteoporosis-related treatments based on strontium ranelate, selective estrogen-receptor modulator (SERM) and parathormone (PTH) in the last 12 months before first injection
• An anticipated need for any forbidden OA treatments during the trial
• Contraindications to HYMOVIS®: hypersensitivity to the product components and infections or skin diseases in the area of the injection site.
• Non-pharmacologic therapy (including physical therapy) for the lower extremities initiated in the month before first injection
• Anticoagulant (coumarinic compound) and heparin

Related to associated diseases

• Severe diseases (liver or renal failure, lung/heart disease, tumor, HIV….)
• Allergy or contra-indication to hyaluronan
• Severe alteration of mobility enabling functional evaluation
• High risk of hemorrhage and risk of infection at the site of injection
• Anticipated need for any surgical or other invasive procedure during the trial including prosthesis in the target knee

Related to patients

• Participation to a therapeutic clinical trial in the last 3 months before first injection
• Under guardianship or judicial protection
• Pregnancy, breastfeeding, planned conception, premenopausal women without contraception, tubal ligation or hysterectomy

Related to MRI counter-indication

• Patient with a pacemaker, an implantable defibrillator, neurosurgical clips, a neurostimulator, cochlear implant, a stent from less than 3 weeks, an insulin pump
• Patient with a ferromagnetic splinter in the body, or having wire sutures
• Serious mobility problem (Parkinson, tremors),
• Claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HYMOVIS Arm; A treatment cycle consists of two injections administered at one week interval. For the purpose of this study, two treatment cycles of two injections of HYMOVIS® at baseline and 6 months will be performed per patient at V1 (Day 0), V2 (Day 7), V5 (Day 180) and V6 (Day 187).	Device: HYMOVIS; HYMOVIS is a clear hydrogel obtained by hydration of the HA-based derivative named HYADD4p5. The conjugate compound is constituted by a partial hexadecylamide of hyaluronic acid, which is produced by a fermentation process.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the variation of type II collagen-specific biomarkers (Coll2-1, Coll2-1NO2 & CTX-II) after HYMOVIS® treatment versus baseline	Measure of the level of Coll2-1, Coll2-1NO2 and CTX-II biomarkers in biological fluids.	Variation of levels of biomarkers from baseline (V1) trough 1 year follow up (V8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation in biomarkers related to cartilage homeostasis (synthesis/degradation balance) after HYMOVIS® treatment vs. baseline	Level of Agrec, COMP, PIIANP, MMP-3 -MPO and IL-6 biomarkers.	ariation of levels of biomarkers from baseline (V1) trough 1 year follow up (V8)
Variation in MRI markers after HYMOVIS® treatment vs. baseline	Semi-quantitative WORMS - T2 relaxation time (T2 mapping) - Cartilage parameters (volume, thickness, curvature)	trough 1 year follow up
Variation in pain and function	Pain and function evaluated with KOOS index - VAS for the mean knee pain over the last 24 hours at rest and while walking pain - VAS for global assessment of disease activity (by patient and by investigator)	trough 1 year follow up
Responder to treatment	Responder rate to treatment (OARSI OMERACT criteria)	trough 1 year follow up
Tolerance and satisfaction	Adverse events and drop-off - Patient satisfaction scale	trough 1 year follow up

Collaborators and Investigators

• Sponsor: Fidia Farmaceutici s.p.a.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): June 6, 2017
• Study Completion (Actual): June 6, 2017

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): March 6, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: MRI; pain; Biomarkers; Hyaluronic acid; Cartilage
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: EQC5-14-02

Drug and device information, study documents

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