patients with symptomatic primary osteoarthritis of the knee MedDRA version: 12.0 Level: LLT Classification code 10031165 Term: Osteoarthritis knee
Conditions
Interventions
Product Name: MEN 16132
Product Code: MEN 16132
Pharmaceutical Form: Solution for injection
CAS Number: 883969-00-4
Current Sponsor code: MEN 16132
Other descriptive name: bradykinin 2 antagonist
Conc
Sponsors
Menarini Ricerche, S.p.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent. 2. Male or female patients =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 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. =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients who are detained or unable 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. 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 immunodeficiency, 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, in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of MEN16132 given by intra-articular injections as four different doses/regimens versus placebo;Secondary Objective: 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.;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. | — |
Countries
Germany, Italy, Spain
Outcome results
None listed