E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with erosive inflammatory osteoarthritis of the interphalangeal joints |
|
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 | 10016686 |
E.1.2 | Term | Finger osteoarthritis |
|
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 |
The objective of this study is to investigate the efficacy of a treatment with etanercept 50 mg sc once weekly during 24 weeks versus placebo, followed by 25 mg sc once weekly for 26 weeks versus placebo as a therapeutic intervention in erosive interphalangeal joint osteoarthritis.
The primary objective is to assess the effect of etanercept on joint pain over 24 weeks in subjects with inflammatory and erosive OA of the hand. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are: -To assess the effect of etanercept on joint pain over 12 weeks in subjects with inflammatory and erosive OA of the hand. -To assess the effect of etanercept on joint pain over 52 weeks in subjects with inflammatory and erosive OA of the hand. -To assess the effect of etanercept on OA specific and generic physical function and joint stiffness over 12, 24 and 52 weeks in subjects with inflammatory and erosive OA of the hand. -To assess the effect of etanercept on patient global assessment over 24 and 52 weeks in subjects with inflammatory and erosive hand OA. -To assess the tolerability and safety of etanercept over 24 and 52 weeks in subjects with inflammatory and erosive OA of the hand. -To assess the effect of etanercept on clinical, laboratory, and imaging assessments over 24 and 52 weeks.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Males and females > 18 years of age. All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 30 days after the last dose of test article. •Subjects with hand OA showing or having suffered from transient inflammatory attacks of the IPJs characteristic for what has been termed ‘inflammatory’ or ‘erosive’ hand OA. •At least 4 OA nodes of the IPJs, e.g. Heberden's and Bouchard's nodes at screening •At least 1 inflamed IP (slight swelling or erythema) at screening •At least 1 IP with positive power Doppler signal at ultrasound •Subjects with hand OA in which at least 1 IPJ has the typical appearance on radiograph of an “E” phase joint as defined by the criteria mentioned above. •OA pain at rest at screening visit of > 30 mm on the VAS •Flare of OA pain with activity at baseline (after NSAID washout) as defined by: >50mm on the VAS •Worsening by > 20 mm on the VAS compared to screening •Use of NSAIDs to treat finger joint pain at least 5 days per week with a stable dose for at least 4 weeks •Inadequate response to at least 1 NSAIDS other than the current NSAID. •Able and willing to self-administer sc injections or have available a suitable person to administer sc injections •Able and willing to give written informed consent and to comply with the requirements of the study protocol.
|
|
E.4 | Principal exclusion criteria |
•Prior treatment with any investigational agent within 30 days, or five half lives of the product, whichever is longer. •Patients suffering from chronic inflammatory rheumatic disease (e.g. rheumatoid arthritis or positive rheumatoid factor or positive anti-CCP antibodies, spondylarthropathy, psoriatic arthritis, haemochromatosis, gout, chondrocalcinosis or other auto-immune diseases •Stable dosage for at least 3 months with chondroitin sulfate, glucosamine, biphosphonate, corticosteroids, tetracyclines and estrogens is allowed. •Prior use of any immunomodulating drug with possible effects on pro-inflammatory cytokine metabolism within 90 days a.o. corticosteroids, methotrexate, sulfasalazine, leflunomide, d-penicillamin, anti-malarials, cytotoxic drugs, TNF blocking agents •If the patient is of child-bearing age, he/she must use effective means of contraception during the study. •Patient who has a known blood coagulation disorder •History of cancer or lymphoproliferative disease other than a successfully and completely treated squamous cell or basal cell carcinoma of the skin or cervical dysplasia, with no recurrence within the last two years •Comorbidities: uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (NYHA III, IV), active inflammatory bowel disease, recent stroke (within three months), chronic leg ulcer and any other condition (e.g,. indwelling urinary catheter) which, in the opinion of the investigator, would put the subject at risk by participation in the protocol. •Positive serology for hepatitis B or C indicating active infection. •History of positive HIV status. •Persistent or recurrent infections or severe infections requiring hospitalization or treatment with iv antibiotics within 30 days, or oral antibiotics within 14 days prior to enrollment. •Female subjects who are breast-feeding. •History of clinically significant drug or alcohol abuse in the last year. •Previous diagnosis or signs of central nervous system demyelinating diseases (e.g., optic neuritis, visual disturbance, gait disorder/ataxia, facial paresis, apraxia). •Medical history of systemic lupus erythematosus or other connective tissue disease, RA, reactive arthritis, psoriasis •Evolutive tuberculosis or other severe infections like sepsis and opportunistic infections •Patients with latent TB (positive PPD skin and/or chest X-ray indicative for TB) or having other risk factors for activation of latent TB, e.g. previous exposure to TB, who have not initiated a TB prophylaxis prior to the first etanercept treatment. •Current or prior history of blood dyscrasias. Abnormal safety baseline blood test e.g. hemoglobin ≤85 g/L; hematocrit ≤27 %; platelet count ≤125 x 109 /L; white blood cell count ≤3.5 x 109 /L; serum creatinine ≥175 µmol/L; aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) ≥2 times the laboratory’s upper limit of normal. •Pre-existing or recent onset CNS demyelinating disease. •Uncontrolled conditions, e.g., diabetes mellitus, hypertension (defined as screening systolic blood pressure > 160mm Hg or screening diastolic blood pressure > 100 mm Hg), severe pulmonary disease requiring hospitalization or supplemental oxygen. •Latex sensitivity. •Reasonable expectation that the subject will not be able to satisfactorily complete the study. History of or current psychiatric illness, alcohol or drug abuse that would interfere with the subject’s ability to comply with protocol requirements or give informed consent. •Employment by the investigator or reporting directly or indirectly to the investigator.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
•Patient assessment of joint pain based on a 100 mm VAS scale |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The last visit of the last subject undergoing the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |