E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active rheumatoid arthritis (RA), patients taking stable doses of methotrexate |
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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 evaluate the ability of KC706 to suppress inflammation (decrease C-reactive protein). To evaluate the safety profile of KC706 administered concomitantly with methotrexate. |
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E.2.2 | Secondary objectives of the trial |
Signs and symptoms of rheumatoid arthritits (RA) will be assessed using the American College of Rheumatology (ACR) Criteria for Improvement based on: Tender joint count, Swollen joint count, Patient’s and Physician's global assessments of disease activity, Patient’s assessment of physical function (Health Assessment Questionnaire, HAQ), Visual Activity Score (VAS) for pain and CRP-primary endpoint. Additional biomarkers may be assessed.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Diagnosis of RA (based on the American Rheumatism Association 1987 revised criteria for the classification of RA). Patients with the American College of Rheumatology (ACR) Global Functional Status Classes I to III will be included 2 The patient’s primary diagnosis should be RA and should have no evidence of any other autoimmune rheumatological condition or overlap syndrome (except sicca syndrome; acceptable only if secondary not primary to RA). The patient may have evidence of osteoarthritis in a joint, secondary to pre-existing rheumatoid disease or may have evidence of osteoarthritis in the spine or in the small joints of the hand, so long as the osteoarthritis does not interfere with the evaluation of the joints targeted for evaluation nor interfere with evaluation of pain and function related to the RA under study 3 Active disease, defined as the presence of at least 8 evaluable swollen joints (out of 44 assessed) and at least 8 evaluable joints tender to palpation (out of 53 assessed) in a joint examination. Evaluable joints are those capable of response to anti-inflammatory therapy 4 CRP ≥20 mg/L 5 Stable mandatory RA medication – all patients should be on the following drugs: Oral or subcutaneous methotrexate (7.5 to 20 mg weekly); dose stable for 6 weeks prior to receiving study drug and dose not anticipated to change during the study 6 Stable optional RA medication, if appropriate: Folic acid supplementation (1 mg/day or 5 mg/week), Nonsteroidal anti-inflammatory drugs (NSAIDs) or Cox-2 inhibitors – doses should be stable for at least 6 weeks prior to dosing with study drug and consistent with labelling recommendations. Only one analgesic drug will be allowed other than low dose aspirin for cardiovascular prophylaxis. Corticosteroids (no more than 10 mg of prednisolone or equivalent)- stable dose for at least 6 weeks prior to dosing with study drug 7 Adequate contraceptive measures must be taken by both sexes. For women of child-bearing potential, 2 methods of contraception (e.g. oral contraceptives and single barrier method or double barrier methods) must be used unless patient is > 1 year post-menopausal or has had sterilization or hysterectomy. 8 Age: 18 - 70 years 9 Body mass index (BMI): 18.0 - 30.0 kg/square metre, inclusive 10 Willing to abstain from alcohol throughout study |
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E.4 | Principal exclusion criteria |
1 Onset of arthritis prior to age 16 2 Use of any other drug, including narcotics, other than; NSAIDs, Cox-2 inhibitors, paracetamol (acetaminophen), corticosteroids for control of pain and/or arthritis or aspirin for cardiovascular prophylaxis. 3 Use of parenteral anti-inflammatory or immune-modulatory treatment (except methotrexate) within four months before receiving study drug. 4 Receipt of intra-articular, intramuscular or intravenous corticosteroids within 6 weeks prior to receiving study drug 5 Known acute infection that may affect CRP levels or active TB, hepatitis (B, C or other) or HIV 6 Current systemic inflammatory condition which may confound CRP assay or other clinical or laboratory evaluations. 7 Clinically significant concurrent medical disease or laboratory abnormalities evidenced by one or more of the following: Hepatobiliary -AST or ALT ≥1.5 times upper limit of normal (ULN), alkaline phosphatase≥2.0 times ULN on 2 consecutive occasions, or -total bilirubin > 80% of ULN for the central laboratory at any time prior to the baseline visit; Renal -serum creatinine > 115 µmol/L, or -significant proteinuria ≥2+ on urinary dip test; Haematology -haemoglobin < 80g/L -leukocytes < 3.5 x 10 9/L -neutrophils < 1.5 x 10 9/L, or -platelets < 100 x 10 9/L; Laboratory teats may be repeated if necessary. Any abnormal values may be discussed with Kemia's medical Monitor before the patient is exluded. 8 Presence or history of malignancy, apart from stable, adequately treated local dermatological cancers. 9 Poorly controlled diabetes. 10 Significant blood loss or donation of blood (>500 mL) within 28 days before randomisation 11 Use of an investigational drug within 1 month of screening or longer if that drug is expected to have long-acting effects (e.g., modulation of B-cell activity) 12 Current or recent history (within 12 months from screening) of drug or substance abuse, including alcohol 13 Known or suspected pregnancy; nursing mothers 14 Clinically significant abnormality on physical examination, laboratory testing, vital signs or electrocardiogram suggestive of significant unstable medical condition 15 Condition which, in the opinion of the investigator, could interfere with participation in the study or would put the patient at unacceptable risk. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |