Evaluation of FLEXOFYTOL® Versus PLACEBO (COPRA)

Evaluation of Efficacy, Tolerance, and Dose Effects of a Curcuma Extract (FLEXOFYTOL®) Versus PLACEBO in Patients With Knee osteoARthritis (COPRA)

This study is a prospective, randomized, double-blind, placebo-controlled with 3 parallel-groups and multicenter trial in patients suffering from knee OA (osteoarthrosis). A first exploratory non comparative study (TILFLEXY002, NCT01909037, Henrotin et al., 2014 BMC Complementary and Alternative Medicine) evaluated the efficacy of FLEXOFYTOL® at the dose of 2x3 caps/day, during a 3-month period, in 22 patients suffering from knee OA, on the serum levels of cartilage-specific and inflammatory biomarkers, on the evaluation of pain and on the global patient assessment of disease activity. This study demonstrated a statistically significant decrease of sColl2-1 cartilage specific biomarker, an early decrease of the ultrasensitive C-reactive protein (CRP), an improvement of the global assessment of the disease by the patient as well as a good tolerance and compliance for the treatment. Results of this exploratory study are encouraging and justify the setup of a randomized, placebo-controlled double blind and dose-ranging trial.

150 patients suffering from symptomatic knee OA will be randomized in 3 parallel groups (50 patients per group). Each patient will be enrolled in the study for 6 months including 4 visits: Inclusion visit (T0), follow-up visits after 1 month (T1), 3 months (T3) and 6 months (T6). A. Primary objective - Evaluate the efficacy of two different dosages of FLEXOFYTOL® versus PLACEBO on arthritis related biomarker coll2-1 and on patient assessment of disease activity in patients suffering from knee OA after a 3 months treatment B. Secondary objectives Evaluate the efficacy of two different dosages of FLEXOFYTOL® versus PLACEBO on arthritis-related and inflammatory biomarkers. Evaluate the efficacy of two different dosages of FL EXOFYTOL® versus PLACEBO on pain and function. Evaluate the tolerance, the compliance and the patients' satisfaction. Evaluate the use of rescue treatments i.e. Paracetamol and oral non-steroidal antiinflammatory drugs (NSAIDs) during the study.

Variation of serum levels of sColl2-1 biomarker between T0 and T3 by specific immunoassays (Enzyme-linked Immunosorbent assay, ELISA).

Variation of Global assessment of disease activity by the patient using a Visual analogue scale (VAS) between T0 and T3.

Variation of serum levels of sColl2-1 (type II collagen degradation) and ultrasensitive CRP (C-reactive protein) biomarkers by specific immunoassays (Enzyme-linked Immunosorbent assay, ELISA).

Evaluation of Incidence of Emergent Adverse Events (AE), drop-outs and safety issues using blood safety analyses on patients with AE (Tolerance).

Evaluate the use of rescue treatments i.e. Paracetamol and oral non-steroidal anti-inflammatory drugs (NSAIDs) during the study.

Secondary outcome 8: Knee injury Osteoarthritis Outcome Score (KOOS) index and its subscale scores using a self-administered questionnaire.

Inclusion Criteria: Male or female between the age of 45 and 80 Exclusion Criteria: Artialis (study coordinator) or Tilman (Sponsor) 's employees Participation to a therapeutic clinical trial in the last 3 months Under guardianship or judicial protection

Henrotin Y, Malaise M, Wittoek R, de Vlam K, Brasseur JP, Luyten FP, Jiangang Q, Van den Berghe M, Uhoda R, Bentin J, De Vroey T, Erpicum L, Donneau AF, Dierckxsens Y. Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study. Arthritis Res Ther. 2019 Jul 27;21(1):179. doi: 10.1186/s13075-019-1960-5.

Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial