Subjects suffering from knee Osteoarthitis MedDRA version: 20.0 Level: PT Classification code 10031161 Term: Osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: WOBENZYM®, enteric-coated tablet
Product Name: Wobenzym
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: Bromelains
CAS Number: 37189-34-7
Other descriptive name: Bromelai
Sponsors
Mucos Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must fulfill all of the following inclusion criteria to be eligible for participation in the study: 1. Male or female = 40 years of age and with BMI = 35 kg/m2; 2. Uni- or bilateral femorotibial knee OA : a. Responding to clinical and radiological criteria of American College of Rheumatology (ACR); b. Symptomatic for more than 6 months in the index knee; c. Radiological Kellgren & Lawrence (K&L) grade II-III in standing x-rays from less than 12 months. 3. Mild-to-Moderate mean knee pain score at rest or at walking over the last 24 hours on the index knee evaluated on VAS (0-100) = 40 at baseline; 4. Able to follow the instructions of the study; 5. Having signed an informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Subjects that meet AT LEAST one of the following criteria will be excluded: Related to knee: 1. Recent macro-trauma of the knee responsible of the symptomatic knee left to the Investigator’s discretion; 2. Concurrent articular disease interfering with the evaluation of pain left to the Investigator’s discretion; 3. Prosthesis in the target knee; 4. Knee swelling requiring corticosteroids local injection. Related to treatments: 5. Analgesics to manage knee pain 24 hours before inclusion visit; 6. Corticosteroids injection in the target knee in the last 3 months; 7. Hyaluronan injection in the target knee in the last 6 months; 8. Arthroscopy in the last 6 months; 9. Oral corticotherapy = 5mg/day (in Prednisolone equivalent) in the last 3 months; 10. Symptomatic slow-acting drugs for osteoarthritis (SYSADOA) or dietary supplement, i.e., curcuma extract, chondroitin, glucosamine, diacerein or avocado-soya unsaponifiables in the last 3 months; 11. An anticipated need for any forbidden treatments during the trial; 12. Contraindications to the product : a. severe hepatic and renal impairment; b. congenital or acquired coagulation disorders, e.g. haemophilia; c. severe liver and/or kidney damage; d. hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption; 13. Hypersensitivity or allergy to the product components or pineapple; 14. Treatments based on strontium ranelate, bisphosphonates, selective estrogen-receptor modulator (SERM) and parathormone (PTH) in the last 12 months; 15. Treatment based on zoledronate in the last 2 years; 16. Treatment based on denosumab in the last 6 months; 17. Treatment with anticoagulants and/or anti-platelet agents, except patients on 100 mg low dose Aspirin that have no identifiable risk of bleeding in their medical history upon discretion of the PI. Related to associated diseases: 18. Any severe, uncontrolled and limiting disease left to the Investigator’s discretion; 19. Patient with widespread pain/depression (e.g. fibromyalgia); 20. Lower or upper extremity surgery or fracture in the last 6 months; 21. Anticipated need for any surgical or other invasive procedure during the trial including prosthesis in the target knee; 22. Severe alteration of mobility enabling functional evaluation. Related to subjects: 23. Close collaborators to the investigational team, the study coordinator (ARTIALIS) or to the Sponsor; 24. Currently participating or having participated in another therapeutic clinical trial in the 3 previous months; 25. Having made a blood donation in the past month; 26. Under guardianship or judicial protection; 27. Pregnancy, breastfeeding, planned conception, or premenopausal women without effective contraception (tablet, patch, ring, diaphragm, implant and intrauterine device, tubal ligation or hysterectomy); 28. Counter-indication to an MRI examination.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the pharmacodynamic profile of an oral enzyme treatment with Bromelain, Trypsin and Rutoside in subjects with Osteoarthritis.;Secondary Objective: The secondary objectives are to evaluate: • Vital signs and anthropomorphic measurements; • Knee pain; • Knee function; • Patient global assessment of disease activity (PGADA); • Patient physical activity; • Body metabolism; • Clinical chemistry; • Joint structure modification; • Volume of joint effusion; • Tolerance; • Compliance; • Responder to treatment.;Primary end point(s): The primary endpoints for evaluation of the pharmacodynamic profile are: • Effects on cartilage biomarkers using immunoassays; • Effects on markers of innate immune response; • Effects on systemic inflammatory markers using immunoassays; • Effects on cellular pathways identified by changes in proteomic profile.;Timepoint(s) of evaluation of this end point: At four timepoints for the entire treatment period (cross-over design, 2 parallel arms): During the first treatment period: - at V0 (baseline) - at V2 (8 weeks post-baseline) During the second treatment period: - at V3 (12 weeks post-baseline and including 4 weeks wash out) - at V5 (20 weeks post-baseline) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: • Blood Pressure (BP), Heart Rate (HR), Temperature, Weight, Height and BMI; • Knee pain at rest and while walking using a Visual Analogue Scale (VAS); • Global score and each of the five subscales scores of the Knee Injury and Osteoarthritis Outcome Score (KOOS) using a self-administered questionnaire; • PGADA using a VAS; • Global physical activity using a connected device; • Concentration of growth factors in serum (e.g. TGF-ß1_ß2_ß3) using immunoassays; • Clinical chemistry measurements using immunoassays: - Concentration of myokines (e.g. myostatin); - Concentration of hemoglobin, hematocrit, erythrocyte count, Triglyceride (TG), Total cholesterol (TC), LDL, HDL, glucose, hsCRP, uric acid, coagulation markers and key hepatic enzymes; • Semi-quantitative joint assessment of knee OA features using MOAKS (MRI Osteoarthritis Knee Score) or WORMS (Whole-Organ Magnetic Resonance Imaging Score); • Volume of joint effusion by magnetic resonance imaging (MRI); • Adverse Events (AE) and drop out; • Tablet count; • Responder rate to treatment defined as changes in knee pain and/or knee function and/or subjects disease activity according to OMERACT OARSI criteria.;Timepoint(s) of evaluation of this end point: To be evaluated at each visit except: - Immunoassays and clinical chemistry which are evaluated at two timepoints for each treatment period (V0, V2 and V3, V5); - MRI which is evaluated at two timepoints for the second treatment period only (V3 and V6). | — |
Countries
Belgium
Contacts
Public ContactArtialis
Artialis SA
Outcome results
None listed