Knee Osteoarthritis
Conditions
Keywords
Hyaluronic acid, MRI, Biomarkers, Cartilage, pain
Brief summary
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.
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.
Interventions
DEVICEHYMOVIS
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.
Sponsors
Fidia Farmaceutici s.p.a.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the variation of type II collagen-specific biomarkers (Coll2-1, Coll2-1NO2 & CTX-II) after HYMOVIS® treatment versus baseline | Variation of levels of biomarkers from baseline (V1) trough 1 year follow up (V8) | Measure of the level of Coll2-1, Coll2-1NO2 and CTX-II biomarkers in biological fluids. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Variation in biomarkers related to cartilage homeostasis (synthesis/degradation balance) after HYMOVIS® treatment vs. baseline | ariation of levels of biomarkers from baseline (V1) trough 1 year follow up (V8) | Level of Agrec, COMP, PIIANP, MMP-3 -MPO and IL-6 biomarkers. |
| Variation in MRI markers after HYMOVIS® treatment vs. baseline | trough 1 year follow up | Semi-quantitative WORMS - T2 relaxation time (T2 mapping) - Cartilage parameters (volume, thickness, curvature) |
| Variation in pain and function | trough 1 year follow up | 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) |
| Responder to treatment | trough 1 year follow up | Responder rate to treatment (OARSI OMERACT criteria) |
| Tolerance and satisfaction | trough 1 year follow up | Adverse events and drop-off - Patient satisfaction scale |
Countries
Belgium, France
Outcome results
None listed