E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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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 |
To assess the effect of PG 760564 on the proportion of patients meeting the American College of Rheumatology 20 response criteria (ACR 20) at 12 weeks |
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E.2.2 | Secondary objectives of the trial |
- To assess the effect of PG 760564 on the proportion of patients meeting the ACR 50 and ACR 70 responses at 12 weeks;
- To assess the effect of PG 760564 on the change from baseline in 28 joint Disease Activity Score (DAS 28) at 12 weeks;
- To assess the effect of PG 760564 on the change from baseline at 12 weeks in the following parameters: Tender joint count Swollen joint count Physician’s global assessment Patient’s global assessment Patient’s assessment of pain Health Assessment Questionnaire (HAQ) score Acute phase reactants [erythrocyte sedimentation rate (ESR) and C reactive protein (CRP)] TNF-alpha, IL-1, and IL-6 Duration of morning stiffness Rheumatoid factor (RF) titer;
- To assess the effect of PG-760564 on time to ACR 20.
- To assess the safety and tolerability of PG 760564 in patients with RA.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients who meet all of the following criteria are eligible for participation in the study:
a. Men and women, 18 to 70 years of age, inclusive, at screening;
b. Who meet ACR criteria for RA, with a documented diagnosis of RA for at least 6 months;
c. Whose functional capacity is class I, II, or III according to the revised criteria of the ACR (Appendix 6);
d. Who have active disease despite treatment with MTX before washout of any DMARDs other than MTX. Active disease for this study will be defined as follows: - At least 6 swollen joints and 6 tender joints; AND, - At least one of the following 3 criteria must be present: ESR of at least 28 mm/hour Elevated CRP Morning stiffness lasting at least 45 minutes;
d. Who have been treated with MTX for at least 24 weeks. The dose of MTX must be stable for at least 8 weeks, at 15-20 mg/week, or at 10 mg/week if that is the maximal tolerated dose, before starting study medication;
e. If female, must be (as documented in the patient notes): - Post menopausal (at least 1 year without spontaneous menses), or - Surgically sterile (if by tubal ligation, must have been performed at least 3 months before entry into the study), or - Using acceptable contraception (e.g., oral, intramuscular, or implanted hormonal contraception, intra-uterine device) for at least 3 months prior to randomization and for the duration of the study including the follow-up period, in conjunction with a barrier method (e.g., condom and spermicide, diaphragm and spermicide) for the duration of the study and during the follow-up period; NOTE: All contraception precautions for MTX must be followed.
f. If sexually-active male, must be surgically sterile (e.g., non-reversed vasectomy with confirmed azoospermia) or use condom during the study and during the follow-up period; NOTE: All contraception precautions for MTX must be followed.
g. Who are willing and able to participate in the study and provide signed informed consent.
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E.4 | Principal exclusion criteria |
- Active or latent tuberculous infection as defined as: history of tuberculosis (TB) OR Chest X ray suggestive of former or current tuberculous infection OR Positive tuberculin skin test with purified protein derivative of tuberculin (PPD) equal to or more than 5 mm in a patient without history of vaccination with bacillus Calmette-Guérin (BCG) OR In Europe, vaccination with BCG and positive PPD equal to or more than 8 mm OR In Europe, vaccination with BCG and positive PPD equal to or more than 5 mm but ≤8 mm and any of the following risk factors: silicosis, residents and employees of high-risk congregate settings, weight loss more than10% of ideal body weight, gastrectomy, jejunoileal bypass - Active listeriosis - History of episode of infection requiring hospitalization within 30 days before screening or episode of infection requiring IV antibiotics within 30 days before sceening or current active infection - History of chronic or recurrent infections, or immunodeficiency - Indwelling catheters - Bronchiectasis - History of uveitis or other inflammatory eye disease - Autoimmune diseases other than RA [MCTD, seronegative spondyloarthropathy, SLE, UCTD, psoriatic arthritis, sarcoidosis, etc.], except Sjogren’s syndrome secondary to RA - Chronic liver diseases, serologic evidence for infection with hep B or hep C - History of alcohol or drug abuse - Abnormal hepatic and renal functions; patients with known elevations of transaminases greater than 1.2 times ULN on 2 or more occasions in the 6 months before screening - Platelets <100 x 109/L - Abnormal WBC and/or significant abnormalities in other complete blood count (CBC) values. Hemoglobin (Hgb) <10 mg/dL - Joint surgery within 2 months of screening - History of lymphoma, leukemia, or lymphoproliferative disorders - History of other malignancies other than treated basal cell carcinoma of the skin - History of demyelinating diseases - History of heart failure, NYHA class III or IV - Pregnant or lactating women, or women who plan to become pregnant - Personal or family history of prolonged QT syndromes. - Other risk factors for torsade de pointes (TdP) - Hypokalemia, hypomagnesemia, or hypocalcemia; - Drugs known to cause prolongation of QT interval (must be off for at least 5 half-lives to be enrolled) - Demonstrated likelihood not to comply with protocol requirements - Current participation in another clinical trial involving active intervention - Known allergy to components of the study medication - History of efficacy failure with etanercept, infliximab, adalimumab, anakinra, and abatacept - History of treatment with B cell depleting therapies and immunoadsorption - History of treatment with p-38 MAP kinase inhibitors - History of treatment with cyclosporine, cyclophosphamide, or other alkylating agents - Other diseases requiring immunosuppressive therapy - Treatment with leflunomide within 6 months prior to study entry - Intra-articular or intramuscular steroids within 4 weeks before screening - Change in NSAID and/or corticosteroid doses within 30 days prior to entry into the study (Day 1 of the washout period) - Treatment with any experimental/investigational therapy within the last 2 months for chemical and 6 months (from screening date) for biologic drugs - Use of the following inducers of CYP 3A4 (carbamazepine, phenobarbital, phenytoin, St John's Wort and troglitazone) or inhibitors of CYP 3A4 (diltiazem, fluvoxamine, grapefruit juice, itraconazole, ketoconazole, mibefradil, nefazodone, troleandomycin, cimetidine, and verapamil) of CYP 3A4; the washout period for these drugs will be 5 days except for phenobarbital for which it will be 21 days - Patients not treated with folic or folinic acid Any other conditions, including important concurrent illnesses (e.g., hypothyroidism) that, in the opinion of the Investigator would jeopardize the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the effect of PG 760564 on the proportion of patients meeting the American College of Rheumatology 20 response criteria (ACR 20) at 12 weeks |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |