E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoarthritis of the knee |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
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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 determine whether Durolane is non-inferior to methylprednisolone, as assessed by level of pain, when each are given as single intra-articular injections for the relief of pain, in the treatment of symptomatic osteoarthritis of the knee at 12 weeks. |
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E.2.2 | Secondary objectives of the trial |
1. If non-inferiority is established, to assess the superiority of Durolane to methylprednisolone. 2. To assess the safety and tolerability of Durolane compared to methylprednisolone in subjects with OA of the knee during the entire blinded phase. 3. To assess the efficacy of Durolane compared to methylprednisolone at 6 weeks, 18 weeks, and 26 weeks after injection.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject (female or male) 35-80 years of age, inclusive; 2. Unilateral knee pain fulfilling ACR criteria for diagnosis of OA (see Appendix 2), most days of the month, for three months; 3. Radiographic evidence of OA in the study knee (Kellgren-Lawrence radiographic score 2 or 3). X-rays obtained within 6 months prior to screening are acceptable; 4. WOMAC pain score of 7-17 in the study knee at both the screening and baseline visits; 5. Subject normally active, not bedridden or confined to a wheelchair, and able to walk 50 meters without the help of a walker, crutches, or a cane; 6. Subject has attempted but not responded adequately to previous non-pharmacological therapy(ies); 7. Subject cooperative and able to communicate effectively with the investigators; 8. Body mass index (BMI) less than or equal to 40 kg/m2; 9. Signed informed consent obtained. |
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E.4 | Principal exclusion criteria |
1. A clinically detectable knee effusion (positive bulge sign or positive patellar tap); 2. Clinically significant contralateral knee OA as evidenced by a WOMAC pain score in this knee >3 (out of 20); 3. Clinically significant hip pain defined by the question, "Have you suffered from pain in or around the hip in most days in the previous month?"; 4. Clinically significant joint pain from joints other than the knee or hip; 5. Previous intra-articular steroid injection into the study knee within the last 3 months; 6. Previous intra-articular HA injection into the study knee within the last 9 months; 7. Previous allergic type reaction to a HA product, a steroid, or lidocaine/related anesthetics; 8. Treatment with analgesics other than paracetamol (acetaminophen) (including topical agents for the knee) within 5 half lives of the drug prior to the baseline visit; 9. Use of opioids other than weak opioids (codeine up to 15 mg per tablet, propoxyphene, dextropropoxyphene) for OA pain on 3 or more days/week within the last month; 10. Use of paracetamol (acetaminophen) or any other analgesic during the 24 hours preceding the baseline visit; 11. Use of systemic glucocorticosteroids (excluding inhaled steroids) within the last 3 months; 12. Treatment with glucosamine/chondroitin sulfate initiated within the past 3 months, or dosage not stable for the past 3 months; 13. Change in physical therapy for the knee within the last three months, or expected change in physical therapy for the knee during the study; 14. Serious injury to the study knee in the previous 6 months; 15. Arthroscopy or other surgical procedure in the study knee within the past 12 months; 16. Any plarmed arthroscopy or other surgical procedure during the study period; 17. Previous history or presence of active septic arthritis in the study knee; 18. Active skin disease or infection in the area of the injection site; 19. Systemic active inflammatory condition or infection, such as rheumatoid arthritis, inflammatory arthritis, ankylosing spondylitis, psoriatic arthritis, reactive arthritis, gout/ acute pseudogout or any other connective tissue disease; 20. Bleeding diathesis or use of anticoagulants (except for acetylsalicylic acid maximum 325 mg/day); 21. Current uncontrolled diabetes mellitus; 22. Known history of drug or alcohol abuse within 6 months prior to screening; 23. Any medical condition that in the opinion ofthe investigator makes the subject unsuitable for inclusion (e.g., severe progressive chronic disease, malignancy, bleeding disorder, fibromyalgia, significant venous or lymphatic stasis) or that, in the opinion of the investigator, are unsuitable for inclusion (e.g., subjects not likely to avoid other therapies, subjects not likely to stay in the study during the whole study period or likely to be unreliable); 24. Pregnant or breastfeeding woman or woman of childbearing potential not practicing adequate contraception; 25. Involvement in other clinical trials that involve treatment or any other intervention within the 30 days prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the WOMAC pain score responder rate, defined as a greater than or equal to 40% and an absolute greater than or equal to 5 point improvement in the WOMAC pain score at 12 weeks following injection of study product at the baseline visit. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
CE-marked Medical Device: Durolane (stabilised hyaluronic acid 20mg/ml) |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 | Information not present in EudraCT |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |