A trial to investigate the efficacy of ASP7692 in patients with pain due to arthritis in the knee
- Conditions
- MedDRA version: 18.1Level: LLTClassification code 10031165Term: Osteoarthritis kneeSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]Osteoarthritis of the knee
- Registration Number
- EUCTR2014-004996-22-ES
- Lead Sponsor
- Astellas Pharma Europe B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 205
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations.
2. Patient is a male or female patient and aged 18 to 75 years, at screening.
3. Patient has a primary diagnosis of OA of the index knee with symptoms for at least 6 months prior to screening and patient meets American College of Rheumatology clinical classification criteria for OA of the knee, defined by the following.
Knee pain and at least 3 of the following 6 (a-f):
a) Age > 50 years
b) Morning stiffness < 30 minutes
c) Crepitus on active motion
d) Bony tenderness
e) Bony enlargement
f) No palpable warmth of synovium
4. Patient has a radiographic image of the index knee (according to the minimum quality criteria for radiographic image as set by the central radiology reader) showing evidence of OA with a Kellgren-Lawrence grade 2 or 3 at screening.
5. Patient has moderate to severe index knee pain (pain due to OA of the knee at least 5 days per week for the last 3 months prior to screening, as determined by patient?s medical history).
6. Patient is ambulatory and the index knee must not contain any orthopedic and/or prosthetic device.
7. WOMAC pain subscale score (with a 48-hour recall period) in the index knee ? 4 at baseline (visit 2 predose, mean of all questions on pain subscale).
8. Mean daily index knee average pain score between ? 4 and ? 9 (0-10 NRS), from the available recordings in the last 4 days prior to visit 2.
9. WOMAC physical function subscale score ? 4 at baseline (visit 2 predose, mean of all questions on the physical function subscale with a 48-hour recall period).
10. Patient is willing to discontinue all current pain medications during the baseline and treatment periods (until day 57) (except for allowed rescue medications). Low dose aspirin for cardioprophylaxis is allowed.
11. Patient is compliant with daily pain recording.
12.Male patient and their female spouse/partners who are of childbearing potential must be using a barrier method* and 1 form of highly effective birth control** starting at screening and continuing throughout the study period and for 90 days after the final study drug administration.
13. Male patient must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
14. Female patient must either:
Be of non childbearing potential:
post-menopausal (defined as at least 1 year without any menses) prior to screening, or
documented surgically sterile
Or, if of childbearing potential:
agree not to try to become pregnant during the study and for 28 days after the final study drug administration,
and have a negative pregnancy test at screening and at baseline (visit 2 predose),
and if heterosexually active, agree to consistently use a barrier method* and 1 form of highly effective birth control** starting at screening and continuing throughout the study period and for 28 days after the final study drug administration15. Female patient must agree not to breastfeed starting at screening and continuing throughout the study period and for 28 days after the final study drug administration.
16. Female patient must not donate ova starting at screening and continuing throughout the study period and for 28 days after the final study drug administration.
17. Patient agrees not to participate in another investigational study from screening through the follow-up period (until da
1.CH of suicide attempt/ suicidal behavior. Suicidal ideation within last 12m or significant risk to commit suicide, judged by inv. at Scr & rando 2.Current or prior psychosis, major depressive disorder or other CS psychiatric disorder 3. Current or prior CS neurologic disease: peripheral neuropathy, stroke, cognitive impairment and seizure 4.CS musculoskeletal disorder (exception OA), CV,GI, endocrinologic (DM allowed if controlled HbA1c? 7.1% and no peripheral neuropathy), hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, dermatologic, renal &/or other major disease judged by inv. 5.Active malignancy or CH of malignancy (except treated nonmelanoma skin cancer) within past 5y. 6.CH of inflammatory arthritis: rheumatoid arthritis or CH of RPOA, osteonecrosis or avascular necrosis of bone &/or joints or other Dx that may increase risk of RPOA 7.Findings suggestive of RPOA/increased risk for RPOA on Scr X-ray of index or non-index joints (central reading) 8.CH of shoulder Sx ,CS trauma or current symptoms: pain or impaired range of motion at shoulder joint 9.Coagulopathy, anticoagulant tt or diagnosed thrombocytopenia or functional platelet disorder 10.CH of paracetamol intolerance or existence of medical condition or use of concomitant medication (CM) being paracetamol contraindicated 11.Naproxen(Nx) contraindication: hypersensitivity to Nx or Nx sodium; asthma, rhinitis, nasal polyps, urticarial or allergic-type reactions after taking aspirin or other NSAIDs; anticipated CABG during study; active or CH of peptic ulceration; active or CH of GI bleeding (exception hemorrhoids) or perforation 12.Tramadol (TD) contraindication: TD hypersensitivity; monoamine oxidase inhibitor used within 2w prior to Scr or during Scr or BSL periods 13.BMI>39 kg/m2. 14.CS abnormality on 12-lead ECG at Scr or BSL (v2 predose) 15.CH of acute coronary syndrome, ischemic or hemorrhagic stroke, transient ischemic attack, coronary or peripheral revascularization procedure, HF, ischemic heart disease, unexplained syncope, cardiac arrest, CS cardiac arrhythmias, heart block (first degree heart block allowed if PR<210msec), torsade de pointes, structural heart disease or personal/family CH of long QT syndrome 16.Resting FR<50or>100bpm; SBP>160mmHg;DBP>90 mmHg at Scr or BSL(v2 predose). If repeat measurement meets above criteria, pt to be excluded 17.CH of unexplained syncopal events or symptomatic orthostatic hypotension at Scr or BSL (v2 predose) 18.According to inv. CS abnormalities in clinical chemistry, hematology or urinalysis at Scr 19.AST, ALT,TBL>1.5 times ULN at Scr 20.GFR?60mL/min/1.73m2(MDRD calculation) at Scr 21.Positive result for HBSLAg, anti-HBc, anti-HAV [IgM], anti-HCV or HIV 1 antibodies &/or HIV 2 at Scr 22.Any IP within 28 d (or 5 half-lives of IP, whichever longer) before Scr or scheduled to receive IP other than blinded study tt during the course of study 23. Pt previously received NGF antibodies 24.Major Sx/orthopedic Sx within 3m before Scr or plans for surgical intervention during study 25.Not suitable candidate for joint replacement & unable to stop chronic NSAID use 26.Intra-articular corticosteroidwithin3m prior to Scr, intraarticular hyaluronic acid within6m prior to Scr or intra-articular local anesthetic within 12m prior to Scr or any of these therapies during Scr or BSL periods 27.Systemic corticosteroids within 30d before Scr or during Scr or BSL periods 28. Any med. or nonmed therapy effective reducing pain of OA o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluate the analgesic efficacy of ASP7962 relative to placebo;Secondary Objective: Secondary<br>Evaluate the efficacy of ASP7962 relative to placebo on pain on walking, function and stiffness Evaluate the time course of efficacy of ASP7962 relative to placebo<br> Evaluate the improvement in overall patient status of ASP7962 relative to placebo<br>Evaluate the safety and tolerability of ASP7962 relative to placebo;Primary end point(s): The primary efficacy endpoint is change from baseline to week 4 in WOMAC pain subscale score.;Timepoint(s) of evaluation of this end point: week 4
- Secondary Outcome Measures
Name Time Method