E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In early RA methotrexate and intra-articular glucocorticoid in combination with adalimumab is better than methotrexate and intra-articular glucocorticoid in achieving control of the disease as assessed by DAS28 < 3.2. |
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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 | 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 |
Inflammatory control as assessed primarily by number of patients who achieve a DAS28 < 3.2 after 12 and 24 months (Zero hypothesis: in early RA methotrexate and intra-articular glucocorticoid in combination with adalimumab is not better than methotrexate and intra-articular glucocorticoid in achieving control of the disease as assessed by DAS28 < 3.2. |
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E.2.2 | Secondary objectives of the trial |
In early RA methotrexate and intra-articular glucocorticoid in combination with adalimumab does not result in an improved outcome compared to methotrexate and intra-articular glucocorticoid alone as assessed by the development of joint erosions and cartilage), and
In early RA methotrexate and intra-articular glucocorticoid in combination with adalimumab does not cause more adverse events including serious adverse events resulting in therapeutic consequences compared to methotrexate and intra-articular glucocorticoid alone). |
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E.2.3 | Trial contains a sub-study | No |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pathogenesis of IL-20 in early rheumatoid arthritis
Pathogenesis of IL-22BP in early rheumatoid arthritis
Chemokine receptors as markers of disease activity, radiological progression and treatment response in early rheumatoid arthritis.
Endothelial progenitor cells (EPC) og cardiovascular changes in early rheumatoid arthritis.
Antibody micro arrays for determination of defense collagens and complement proteins in patients with early reheumatoid arthritis before and after conventional DMARD and/or anti-TNF-alpha inhibitor treatment: analysis and correlation to disease activity, progression of joint destruction, and treatment response
Adiponectin as a marker for disease activity, radiological progression and treatment response in early rheumatoid arthritis.
Inflammatory- and bone biomarkers as well as gene and micro RNA array patterns in early rheumatoid arthritis.
Validation of cartilage and bone markers in early rheumatoid arthritis.
New markers for antigen presentation and autoimmunity Study 1: The role of sortilin for MHC-II-mediated antigen presentation Study 2: Association between human MHC2TA promoter III polymorphism, MHC-II expression and rheumatoid arthritis Study 3: CD163 expression as prognostic marker for pharmacological response and disease progression in patients with early rheumatoid arthritis
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E.3 | Principal inclusion criteria |
Patients (³ 18 years) with rheumatoid arthritis according to the ACR classification criteria (1) who have been diagnosed £ 6 months.
Moderate to severe rheumatoid arthritis defined as DAS28 (CRP-based) > 3.2.
Negative pregnancy test (serum HCG) for women of childbearing potential prior to trial start. (Non-fertile women are defined as postmenopausal for at least 1 year or surgical sterilisation (bilateral tubal ligation, bilateral oophorectomy or hystorectomy)). Fertile women included in the trial should use contraception during the entire trial period (i.e. one of the following methods: Oral contraception, intrauterine device (IUD), depot injection of progesterone, subdermal implantation, contraceptive vaginal ring, transdermal depot plaster). In addition, contraception should be used for a period of 150 days after any discontinuation of trial medicine.
Ability and willingness to inject the sc. injections him/herself or to have an assistant give the injections.
Ability and willingness to give written informed consent and to meet the requirements of the trial protocol.
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E.4 | Principal exclusion criteria |
Persons with latent TB (positive Mantoux test (>10 mm), positive inoculation of mycobacterium in tissue samples and/or chest X-ray indicating TB) or other risk factors for activation of untreated latent TB
Active or recurrent infections or severe infections requiring hospitalization or treatment with i.v. antibiotics within the last 30 days or oral antibiotics within the last 14 days prior to inclusion
Positive serology for Hepatitis B or C indicating active infection.
Medical history with positive HIV status (Check of HIV test upon suspicion).
Medical history with histoplasmosis or listeriosis.
Previous cancer or lymph proliferative disease except from completely well treated squamous cell carcinoma, basal cell skin carcinoma or cervix dysplasia.
Previous diagnosis or signs of demyelinized disease in the CNS system (e.g. optic neuritis, visual disorder, disturbed gait, facial paralysis, apraxia).
Severe renal insufficiency (creatinine clearance < 35 ml/min - nomogram).
Affected liver function: Liver enzymes > 2 x above normal limit value.
Clinical significant drug or alcohol abuse during the past year and/or current daily alcohol consumption.
Diabetes, unstable ischemic heart disease, heart insufficiency (NYHA III-IV), active chronic inflammatory intestinal disease, recent cerebral apoplexia (within 3 months), chronic leg ulcer or any other condition (e.g. catheter a demeure) imposing an increased risk on to the subject, if he/she participates in the protocol, as judged by investigator.
Anticoagulant therapy.
Pregnancy or breast-feeding.
Other inflammatory rheumatic diseases.
Aggressive parvovirus B19 infection.
Previous treatment with one or more DMARDs.
Glucocorticosteroid treatment within the last 4 weeks (except nasal and inhalation steroids).
Contraindications for trial medicine.
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E.5 End points |
E.5.1 | Primary end point(s) |
Assuming that 90% of patients treated with adalimumab and 70% of patients treated with placebo achieve the primary clinical endpoint (DAS < 3.2) after 12 and 24 months.
Assuming that 90% of patients treated with adalimumab and 70% of patients treated with placebo achieve the primary radiographic endpoint (no radiographic progression) after 12 and 24 months. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 18 |
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 | 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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |