A trial to investigate the efficacy of ASP7692 in patients with pain due to arthritis in the knee
- Conditions
- Osteoarthritis of the kneeMedDRA version: 18.1Level: LLTClassification code 10031165Term: Osteoarthritis kneeSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2014-004996-22-BE
- 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 administration.
15. 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 f
3 Current or prior clinically significant neurologic disease, including but not limited to peripheral neuropathy, stroke, cognitive impairment and seizure.
4 Any clinically significant, musculoskeletal disorder (with the exception of OA), cardiovascular, gastrointestinal, endocrinologic (diabetes mellitus is allowed if controlled [glycated hemoglobin (HbA1c) = 7.1%] and no peripheral neuropathy), hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, dermatologic, renal and/or other major disease.
6 History of inflammatory arthritis, including rheumatoid arthritis or a history of RPOA, osteonecrosis or avascular necrosis of bone and/or joints or has other diagnoses that may increase the risk of RPOA.
7 Findings suggestive of RPOA or increased risk for RPOA on screening radiographs of either index or non-index joints.
8 History of shoulder surgery, clinically significant trauma or current symptoms, including pain or impaired range of motion at shoulder joint.
9 Coagulopathy, receiving anticoagulants or diagnosed with thrombocytopenia or a functional platelet disorder.
10 History of paracetamol intolerance, or medical condition or use of concomitant medication for which paracetamol is contraindicated.
11 Any contraindication to naproxen
12 Any contraindication to tramadol
15 History of acute coronary syndrome, ischemic or hemorrhagic stroke, transient ischemic attack, coronary or peripheral revascularization procedure, heart failure, ischemic heart disease, unexplained syncope, cardiac arrest, clinically significant cardiac arrhythmias (including atrial fibrillation or flutter), heart block (first degree heart block is allowed provided PR interval is not greater than 210 msec), torsade de pointes, structural heart disease or a personal or family history of long QT syndrome.
16 Resting pulse rate < 50 or > 100 bpm; SBP > 160 mm Hg; diastolic blood pressure (DBP) > 90 mm Hg at screening or baseline.
17 History of unexplained syncopal events or has symptomatic orthostatic hypotension at screening or baseline , defined as postural related symptoms and at least one of the following: standing SBP = 20 mm Hg lower than supine SBP, standing DBP = 10 mm Hg lower than supine DBP.
19 Any liver tests (AST, alanine aminotransferase [ALT], total bilirubin [TBL]) > 1.5 times the ULN at screening.
20 Estimated glomerular filtration rate of = 60 mL/min/1.73 m2 (MDRD calculation) at screening.
24 Previously received antibodies to NGF.
26 Not a suitable candidate for joint replacement surgery and unable to stop chronic NSAID use.
27 Received intra-articular corticosteroid within 3 months prior to screening, intra-articular hyaluronic acid within 6 months prior to screening or intra-articular local anesthetic within 12 months prior to screening or any of these therapies during the screening or baseline periods.
28 Received systemic corticosteroids within the past 30 days before screening or during the screening or baseline periods (topical, nasal and inhaled corticosteroids are permitted).
29 Received any medications or nonmedication therapy with efficacy in reducing pain of OA of the knee, including over-the-counter (OTC) products (with the exception of ice packs, rest and paracetamol) during the baseline period.
30 Patient has started or stopped physiotherapy, acupuncture or transcutaneous electrical nerve stimulation related to treatment of the index knee within 4 weeks prior to screening or during the screening or baseli
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<br>? 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): 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