E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pacientes afectos de osteoartritis primaria de rodilla en fase sintomática
PATIENTS WITH SYMPTOMATIC PRIMARY OSTEOARTHRITIS OF THE KNEE |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031165 |
E.1.2 | Term | Osteoarthritis knee |
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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 |
To evaluate the efficacy of MEN16132 given by intra-articular injections as four different doses/regimens versus placebo |
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E.2.2 | Secondary objectives of the trial |
To evaluate - the dose-effect relationship of MEN16132 to support the choice of the dose/ schedule to be studied in the subsequent clinical phase III study; - the time to onset and the duration of effect; - the safety and tolerability of MEN16132 given as 1 mL solution for intra-articular injection up to 0.5 mg dose for a cumulative dose up to 1.0 mg; - the population pharmacokinetics of MEN16132 in patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent. 2. Male or female patients > or = 40 years old. 3. Women of childbearing potential are eligible to participate in the study if their pregnancy test (serum ß-hCG) is negative at screening, they are not nursing, and they use an effective method of contraception until all follow-up procedures are complete. Methods of contraception considered effective include oral, injectable or implanted hormonal contraceptive agents, hormone containing intra-uterine devices with failure rates <1% per year. 4. Symptomatic primary knee osteoarthritis (ACR criteria1) since > or = 6 months prior to screening, with documented 'minimal to moderate' radiological se-verity (i.e. Kellgren Lawrence Grade 2 or 3) based on X-ray not older than 6 months, and representing an indication for intra-articular drug injection. 5. >50 mm VAS pain score assigned to the index knee at WOMAC VA 3.1-A1 (pain while walking on a flat surface). 6. >125 mm VAS pain score assigned to the index knee at WOMAC VA 3.1 A subscore (total pain). 7. Pain in the index knee on at least 50% of the days in the month preceding the screening. 8. Minimum flexion of 90 degrees in both knees. 9. Ability to perform the 15 m walk test without the support of crutches or other assistive devices. 10. Willingness to discontinue all pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics) prior to randomisation and for the entire course of the study with a minimum wash-out of 1 or 2 weeks for drugs with short (i.e. < 5 hours) or longer half-life, respectively. NOTE: This does not include paracetamol, up to 1000 mg/day, as rescue medication and low dose aspirin for cardioprotection, up to 100 mg/day or other salicilates at equivalent doses. 11. Willingness to refrain from paracetamol use 48 hours prior to any study visit. |
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E.4 | Principal exclusion criteria |
1. Inability to personally provide written informed consent (e.g. patients with significant psychiatric illness). 2. Inability to understand or collaborate throughout the study. 3. Subjects who participated in another clinical trial within 30 days prior randomisation. 4. Patients with Kellgren & Lawrence Grade I or IV (doubtful or severe) osteoarthritis of the knee. 5. Knee condition representing an indication for surgery (e.g. significant axial deviation of the knee, severe medio-lateral and/or anterior-posterior instability, severe bone / joint deformity, severe osteoarthritis). 6. Inflammatory or crystal arthropathies (e.g. rheumatoid arthritis, lupus erythematosus, psoriatic arthritis, gout). 7. Patients with acute fractures, severe loss of bone density, bone necrosis. 8. Patients with isolated patella-femoral syndrome or chondromalacia. 9. Patients with OA predominant in the lateral compartment or any significant valgus deformity. 10. Patients with any other disease or condition interfering with the free use and evaluation of the index knee for the 3 month duration of the trial (e.g. cancer, congenital defects, spine osteoarthritis). 11. Major injury or surgery to the index knee within the previous 12 months prior to screening. 12. Severe hip osteoarthritis ipsilateral to index knee. 13. Any pain >30 mm VAS that could interfere with the assessment of index knee pain (e.g. pain in any other part of the lower extremities, pain radiating to the knee). 14. Any pharmacological or non-pharmacological treatment started or changed during 4 weeks prior to randomisation or likely to be changed during the duration of the study, e.g. acupuncture. Stable treatment for stable chronic disease (e.g. hypertension, coronary heart disease, diabetes, osteoporosis, COPD, asthma incl. inhaled steroids, or physical therapy) is permitted as is the use of oral contraception or hormone replacement therapy IF patients are expected to remain on constant doses throughout the course of the study. 15. Use of systemic or topical corticosteroids >10 mg prednisolone equivalent per day during 30 days prior to randomisation. 16. Use of any pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, anal-gesics during 1 or 2 weeks prior to randomisation for drugs with short (i.e. < 5 hours) or longer half-life, respectively. NOTE: This does not include paracetamol, up to 1000 mg/day, as rescue medication until 48 hours prior to each study Visit, and low dose aspirin for cardioprotection, up to 100 mg/day or other salicilates at equivalent doses. 17. Any acute or newly diagnosed disease/condition requiring treatment. 18. Any chronic disease/condition requiring treatment modification. 19. History of hypersensitivity / allergy to drugs including paracetamol. 20. Patients with any clinically significant abnormal diagnostic test result that may represent a health risk, impact the study or affect the patient's ability to complete the study. 21. Patients with liver disease (i.e. ALT and/or AST >2x upper limit of normal [ULN], and/or conjugated bilirubin >2x ULN). 22. Patients with severe renal insufficiency (serum creatinine >2 mg/dL). 23. Any sign of significant inflammation or infection (e.g. reddening or warmth of the knee, fever, increased CRP, leukocytosis). 24. Any skin disorder or infection overlying the index knee. 25. Previous infection of the index knee. 26. Any intra-articular or local peri-articular punction, injection or surgery to the index knee during the 6 months prior to screening. 27. Patients with bleeding diathesis or on therapy with anticoagulants (low dose aspirin, not exceeding 100 mg per day or other salicilates at equivalent doses are permitted). 28. Significant peri-articular calcification. 29. Previous ligament reconstruction at the index knee. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis will be based on the improvement of the index knee pain in the intention to treat (ITT) population. It will be assessed based on the WOMAC VA 3.1 A pain subscore (0-500 mm) which is the sum of the VAS score (0-100 mm) attributed by the patient to each of the 5 questions referring to pain experienced during the preceding 48 hours. The treatment effect will be assessed on the WOMAC VA 3.1 A pain subscore at baseline (Visit 2) versus those recorded over the 3 subsequent weeks (Visits 3, 4 and 5) representing the 3 weeks following the first drug administration. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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End of trial is defined as last patient last visit |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |