A LONG-TERM, RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP,PLACEBO-CONTROLLED, RADIOGRAPHIC STUDY TO INVESTIGATE THESAFETY AND EFFICACY OF ORALLY ADMINISTERED SD-6010 IN SUBJECTSWITH SYMPTOMATIC OSTEOARTHRITIS OF THE KNEE
- Conditions
- OsteoarthritisMedDRA version: 9.1Level: LLTClassification code 10023476Term: Knee osteoarthritis
- Registration Number
- EUCTR2007-001457-26-SK
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 1400
1. Has provided written informed consent and is willing to comply with scheduled visits, treatment plan, radiographs, laboratory tests, and other trial procedures;
2. Is a female aged =40 years with a BMI =30 and <40 kg/m2;
3. In the past, has been diagnosed with knee OA and has had knee symptoms in the past year defined as:
• Pain, aching or stiffness on most days of a month; and/or
• Used a medication (other than potent opioids) for treatment of knee pain on most days of a month;
4. Has a current level of pain (outside of acute flare) in at least 1 knee characterized by a WOMAC Pain subscale score of between 6 and 12, inclusive (where the range of sub-scores is 0-20); Note: Pain must be characterized as a subject’s normal day-to-day pain while on standard of care medication and not the pain associated with an acute flare.
5. Has been on the same standard of care medication(s) for OA pain in the knee(s) for at least 3 months and on a stable dosing regimen for at least 4 weeks preceding the first dose of study medication (stable defined as: Doses and frequency of administration remain unchanged);
6. Is of non-childbearing potential, if 1 of the 2 categories below is satisfied:
• Is =45 years of age and amenorrheic for at least 2 years, or
• Has proof of a physician documented hysterectomy and/or bilateral oophorectomy;
Note: Females not meeting the non-childbearing rules above or having undergone tubal ligation will be considered of childbearing potential for this study (refer to #7 next).
7. If of childbearing potential, has agreed that when sexually active, to use the protocoldesignated effective methods of contraception.
Central Imaging Core Laboratory Criteria for Inclusion
Subjects meeting the following Screen 1 inclusion criteria by radiography as assessed through the modified Lyon-schuss X-ray will be semi-qualified for Screen 2. Criteria 1-6 below will be assessed by the independent Central Reader and communicated back to the Central Imaging Core Laboratory, which will then assess the results against the OA history taken at the Screen 1 visit as the final step in determining which subjects will be invited back for Screen 2. A yes” answer to
each criteria is needed to continue screening.
1. A KLG 2 or 3 AND a medial tibiofemoral minimum JSW =2 mm in the study knee;
2. A KLG <4 in the contralateral knee;
3. An anatomic axis angle between 184 and 174 degrees inclusive in the study knee;
4. The lateral minimum joint space width (JSW) > the medial minimum JSW in the study knee;
5. No radiological findings such as, but not limited to avascular necrosis, fracture, infection, gout, Paget’s disease, osteopetrosis, osteochondritis, or other pathologies in the study knee.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Subjects must meet all of the following Investigator Level inclusion criteria to advance to the knee imaging phase of Screen 1. Failure to meet these criteria will result in a Screen Fail for the subject
Subjects presenting with any of the following will not be eligible for knee imaging at the Radiology Center. A yes” response to any criterion below will result in a Screen Fail for the subject:
1. Subjects with a history of:
A diagnosis of any other rheumatic disease
Current, severe, uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological disease, or any other condition which would make the subject unsuitable for the study within 6 months preceding the Screen 1 visit.
Clinically significant infections (acute infection or those requiring hospitalization or
visit;
An active malignancy of any type or history of a malignancy
Any known diseases or conditions that may involve the knees
Significant trauma to the knees (including arthroscopy or significant injury to ligaments or menisci of the knee within 1 year preceding the Screen 1 visit
2. Subjects presenting with:
A verified systolic blood pressure >150 mm Hg (if untreated for hypertension) or greater than 160 mm Hg (if treated for hypertension) and/or a diastolic blood pressure greater than 90 mm Hg;
An ECG finding considered by the Investigator to be clinically significant;
Any morbidities that would curtail work-related or leisure time physical activities such that these morbidities would contribute to increases in sedentary behaviors;
Chronic potent opioid use;
Any condition possibly affecting oral drug absorption;
Anticipated need for knee or hip surgery in the next 2 years;
Exacerbation of OA pain in either knee requiring a change in stable treatment within 4 weeks of the Screen 1 visit;
Symptomatic OA of either hip by history or elicited on physical examination that may
confound the interpretation of knee pain;
Clinically significant non-articular musculoskeletal pain that cannot be distinguished
from knee OA;
Intra-articular hyaluronic acid to either knee within 6 months preceding the Screen 1
visit;
Use of any investigational drug within 1 month preceding the Screen 1 visit;
3. Pregnant or breastfeeding females;
4. Anticipating a move out of the area of the clinic in the next 2 years.
5. A subject anticipating or participating in a defined weight loss program for any reason in the next 2 years.
Exclusion Criteria at Screen 2
Subjects advancing to Screen 2 will have successfully completed the cursory review of safety, have passed the Investigator Level inclusion/exclusion tests of Screen 1, and have been successfully screened by the Central Reader and the Central Imaging Core Laboratory. The Screen 2 visit will essentially complete all other safety screens for eligibility and establish the baseline values for safety and for the majority of secondary efficacy assessments.
Subjects presenting with any of the following will not qualify for randomization. Failure to meet these criteria will result in a Screen Fail for the subject:
1. Clinical signs of tuberculosis (TB) such as generalized tiredness or weakness, weight loss, fever, night sweats, coughing, chest pain, coughing up sputum and/or blood, shortness of breath, x-ray showing infiltrates or fibrosis suggestive of TB;
2. Currently undergoing treatment for TB;
3. Evidence of latent TB infection (LTBI) without documented evidence of treatment with an acceptable c
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the disease modifying efficacy of SD-6010 50 mg and 200 mg QD compared to placebo in reducing the rate of progression of OA as assessed by radiographic JSN in the medial tibiofemoral compartment of the study knee of obese women with knee OA.;Secondary Objective: 1. To assess the safety and tolerability of SD-6010 50 mg and 200 mg QD administered long-term to obese women with knee OA;<br>2.To assess the clinical benefit of SD-6010 50 mg and 200 mg QD in obese women<br>with knee OA as measured by the clinical endpoints including, but not limited to,<br>WOMAC, pain VAS (visual analog scale), changes in background pain therapy and<br>use of rescue medication in the study knee.;Primary end point(s): The progression rate of Joint space narrowing (JSN)
- Secondary Outcome Measures
Name Time Method