E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 |
The main objective of this study is to assess and compare the proportion of subjects who achieve low disease activity as defined by a clinical response (DAS28(CRP) <3.2) at week 26 with four different regimens of methotrexate in combination with adalimumab in order to determine the dose-response pattern of methotrexate in combination with adalimumab patients with early rheumatoid arthritis (RA).
The study is also designed to evaluate the pharmacokinetics and safety of 4 different regimens of Methotrexate in combination with adalimumab in patients with early RA. |
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E.2.2 | Secondary objectives of the trial |
● Response defined by ACR 20/50/70/90/100 criteria at Week 26
● ΔmTSS at Week 26
● Proportion of subjects with no radiographic progression (ΔmTSS ≤ 0.5) at Week 26
● DAS28(CRP) < 2.6 at Week 26
● Change in HAQ-DI at Week 26
● Proportion of subjects with ΔHAQ-DI ≥ –0.22 at Week 26 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetic analysis is optional and requires subject's prior consent. DNA samples may be analyzed for genetic factors contributing to the subject's response to study treatment in terms of pharmacokinetics, pharmacodynamics, efficacy, tolerability, and safety. |
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E.3 | Principal inclusion criteria |
Inclusion Criteria:
•Male and female subjects at least 18 years of age.
•Subject has a diagnosis of Rheumatoid Arthritis (RA) as defined by either the 1987-revised American College of Rheumatology (ACR) classification criteria or the new ACR/ European League Against Rheumatism (EULAR) diagnostic criteria for RA 2010 and has a disease duration of less than 1 year from diagnosis by a licensed health care provider.
•Subject must meet the following criteria: At least 6 swollen joints out of 66 assessed (at the Screening and Baseline visits), at least 8 tender joints out of 68 assessed (at the Screening and Baseline visits).
•Subject is judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening. |
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E.4 | Principal exclusion criteria |
Exclusion Criteria:
•Subject has previous exposure to any systemic biologic therapy including adalimumab.
•Subject has been previously treated with > 1 disease modifying antirheumatic drugs (DMARDs) or with Methotrexate (MTX).
•Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study).
•Subject has chronic arthritis diagnosed before age 17 years.
•History of invasive fungal infection (e.g., listeriosis and histoplasmosis), chronic or active Hepatitis B or Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis (TB).
•Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit.
•Female subject who is pregnant or breast-feeding or considering becoming pregnant |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is the proportion of subjects achieving low disease activity as defined by a clinical response (DAS28(CRP) < 3.2) at Week 26
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•American College of Rheumatology (ACR) 20/50/70/90/100 criteria [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
Response defined by ACR 20/50/70/90/100 criteria at Week 26
•Change in modified Total Sharp Score (ΔmTSS) [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
Response defined by no radiographic progression (ΔmTSS ≤ 0.5) at Week 26
•Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
Change in HAQ-DI at Week 26, Proportion of subjects with Δ HAQ-DI ≥ -0.22 at Week 26
•DAS28(CRP) [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
DAS28(CRP) < 2.6 at Week 26 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Voluntary consent to pharmacogenetic analysis. |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | No |
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 |
Argentina |
Canada |
Puerto Rico |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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As per the protocol, the end-of-study is defined as the date of the last subject's last visit or the actual date of follow-up contact, whichever is later. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |