|E.1 Medical condition or disease under investigation |
|E.1.1||Medical condition(s) being investigated || |
|Moderate to severe pain associated with osteoarthritis of the knee |
|E.1.1.1||Medical condition in easily understood language || |
|Pain due to osteoarthritis of the knee |
|E.1.1.2||Therapeutic area ||Diseases [C] - Musculoskeletal Diseases [C05] |
|MedDRA Classification |
|E.1.2 Medical condition or disease under investigation |
|E.1.2||Version ||21.1 |
|E.1.2||Level ||LLT |
|E.1.2||Classification code ||10023476 |
|E.1.2||Term ||Knee osteoarthritis |
|E.1.2||System Organ Class ||100000004859 |
|E.1.3||Condition being studied is a rare disease || No |
|E.2 Objective of the trial |
|E.2.1||Main objective of the trial || |
|Demonstrate the analgesic efficacy of intra-articular RTX-GRT7039 compared with placebo. |
|E.2.2||Secondary objectives of the trial || |
|• Demonstrate the analgesic efficacy of intra-articular RTX-GRT7039 compared with placebo. |
• Demonstrate the efficacy of intra-articular RTX-GRT7039 on function compared with placebo.
• To assess the safety and tolerability of intra-articular RTX-GRT7039.
|E.2.3||Trial contains a sub-study || No |
|E.3||Principal inclusion criteria || |
|• ≥ 18 years of age at the screening visit. |
• Body Mass Index (BMI) ≤ 40.0 kg/m2.
• Diagnosis of osteoarthritis of the knee based on American College of Rheumatology criteria and functional capacity class of I-III.
• Moderate to severe osteoarthritis at baseline.
• Documented history indicating that subject has insufficient pain relief with optimal standard of care (SoC).
• The investigator does not consider that any additional benefit can reasonably be expected from further adjustments to the patient's pain treatment.
|E.4||Principal exclusion criteria|| |
|• The subject had an intra-articular injection of either corticosteroid or intra-articular visco-supplementation (i.e., hyaluronic acid) into the index knee within 3 months. |
• The subject had an injection of platelet-rich plasma into the index knee within 6 months.
• The subject applied topical capsaicin on the index knee within 3 months.
• Pre-existing rapidly progressing osteoarthritis (RPOA) Type I or Type II, osteonecrosis, subchondral insufficiency fracture, atrophic osteoarthritis, or the subject has knee pain attributable to disease other than osteoarthritis.
• Other conditions that could confound discrimination of pain assessment in the index knee.
• Clinically significant disease(s) or condition(s) that may affect efficacy or safety assessments, or any other reason which, in the investigator's opinion, may preclude the subject's participation in the full duration of the trial.
• History of severe allergic or anaphylactic reactions.
• History of significant trauma or surgery, or surgery planned during the trial period, related to the knee.
|E.5 End points |
|E.5.1||Primary end point(s)|| |
|1) Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score in the index knee. |
|E.5.1.1||Timepoint(s) of evaluation of this end point|| |
|1) From baseline (assessment at Visit 2) to Visit 5. |
|E.5.2||Secondary end point(s)|| |
|1) Change in WOMAC pain subscale score in the index knee based on the 11-point numeric rating scale (NRS). |
2) Change in WOMAC physical function subscale score.
3) Incidence of treatment-emergent adverse events (TEAEs). Incidence of TEAEs leading to discontinuation in the Treatment and Follow-up Period after the first and after the second injection, respectively. Incidence of related TEAEs representing structural changes of the knee joint as visualized by the imaging methods (X-ray and/or magnetic resonance imaging [MRI]).
|E.5.2.1||Timepoint(s) of evaluation of this end point|| |
|1) From baseline (assessment at Visit 2) to Visit 6 to Visit 10. |
2) From baseline (assessment at Visit 2) to Visit 5 to Visit 6 to Visit 10.
3) From baseline (assessment at Visit 2) to Visit 10. (end of trial).
|E.6 and E.7 Scope of the trial |
|E.6||Scope of the trial |
|E.6.1||Diagnosis|| No |
|E.6.2||Prophylaxis|| No |
|E.6.3||Therapy|| Yes |
|E.6.4||Safety|| Yes |
|E.6.5||Efficacy|| Yes |
|E.6.6||Pharmacokinetic|| No |
|E.6.7||Pharmacodynamic|| No |
|E.6.8||Bioequivalence|| No |
|E.6.9||Dose response|| No |
|E.6.10||Pharmacogenetic|| No |
|E.6.11||Pharmacogenomic|| No |
|E.6.12||Pharmacoeconomic|| No |
|E.6.13||Others|| No |
|E.7||Trial type and phase |
|E.7.1||Human pharmacology (Phase I)|| No |
|E.7.1.1||First administration to humans|| No |
|E.7.1.2||Bioequivalence study|| No |
|E.7.1.3||Other|| No |
|E.184.108.40.206||Other trial type description|| |
|E.7.2||Therapeutic exploratory (Phase II)|| No |
|E.7.3||Therapeutic confirmatory (Phase III)|| Yes |
|E.7.4||Therapeutic use (Phase IV)|| No |
|E.8 Design of the trial |
|E.8.1||Controlled|| Yes |
|E.8.1.1||Randomised|| Yes |
|E.8.1.2||Open|| No |
|E.8.1.3||Single blind|| No |
|E.8.1.4||Double blind || Yes |
|E.8.1.5||Parallel group|| Yes |
|E.8.1.6||Cross over || No |
|E.8.1.7||Other|| No |
|E.8.2|| Comparator of controlled trial |
|E.8.2.1||Other medicinal product(s)|| No |
|E.8.2.2||Placebo || Yes |
|E.8.2.3||Other|| No |
|E.8.2.4||Number of treatment arms in the trial||2 |
|E.8.3|| The trial involves single site in the Member State concerned || No |
|E.8.4|| The trial involves multiple sites in the Member State concerned || Yes |
|E.8.4.1||Number of sites anticipated in Member State concerned||11 |
|E.8.5||The trial involves multiple Member States|| Yes |
|E.8.5.1||Number of sites anticipated in the EEA||43 |
|E.8.6 Trial involving sites outside the EEA |
|E.8.6.1||Trial being conducted both within and outside the EEA|| Yes |
|E.8.6.2||Trial being conducted completely outside of the EEA|| No |
|E.8.6.3||If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned|| |
|E.8.7||Trial has a data monitoring committee|| No |
|E.8.8|| Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial || |
|E.8.9 Initial estimate of the duration of the trial |
|E.8.9.1||In the Member State concerned years||3 |
|E.8.9.1||In the Member State concerned months|| |
|E.8.9.1||In the Member State concerned days|| |
|E.8.9.2||In all countries concerned by the trial years||3 |