E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis |
Reumatoid artrit |
|
E.1.1.1 | Medical condition in easily understood language |
Rheumatoid arthritis |
Ledgångsreumatism |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
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 primary objective of this study is to study difference in DAS28 over 12 months of follow up in patients with newly diagnosed RA randomized to oral or subcutaneous methotrexate |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to study the treatment-efficacy in other aspects, drug retention after 24 months as well as number of adverse events Is there a change in gut microbiota driven by per oral methotrexate that is different from the change driven by subcutaneous methotrexate What are the trade-offs newly diagnosed patients with RA willing to make with regard to treatment with methotrexate? What are the maximum acceptable levels of risks for newly diagnosed patients with RA? Is there a difference in health-related quality of life in patients treated with per oral methotrexate compared to patients treated with subcutaneous methotrexate during the first two years of treatment? Is it possible to further model a difference in health-related quality of life during further follow up of these individuals? |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be included in the study, subjects must meet the following criteria: • The subject has given written consent to participate in the study • Diagnosis of rheumatoid arthritis by rheumatologist fulfilling 2010 Rheumatoid Arthritis Classification Criteria • Indication of methotrexate • 18-95 years of age • Women of Childbearing Capacity (WOCBC) must: a) Comply to use of highly effective contraception methods during the course of the trial. b) Have a negative pregnancy test. • Male patients included in the study that have fertile female partners must use adequate contraception within their relationship during the same period of time
|
|
E.4 | Principal exclusion criteria |
Subjects must not be included in the study if any of the following criteria are met: • Contraindications for methotrexate • Previous treatment with any DMARD within the last five years • Known or suspected allergies against methotrexate or any other substance in the given medication • Anamnestic information on pregnancy, breastfeeding, or planned pregnancy • Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation or inability to answer questionnaire in written Swedish • Treatment or disease which, according to the investigator, can affect treatment or study results. • Fear of needles leading to not being able to use subcutaneous injections • For the study in gut microbiota: Use of antibiotics or probiotics within the last 3 months |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary variable: At inclusion and at all timepoints of follow up register DAS28, calculated using the following formula: DAS28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 0.014 * [general health] |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At each visit (after 0, 3, 6, 12 and 24 months) |
|
E.5.2 | Secondary end point(s) |
Number of swollen joints Number of tender joints HAQ VAS pain VAS general health VAS fatigue Doctor’s global assessment Number of individuals remaining on the designated drug (drug retention) including number of individuals prescribed biologic treatment Number of patient´s contact with any health care giver All other medications, including corticosteroids, other csDMARDs, biologics, intraarticular injections as well as change in dosage or administration route of methotrexate ESR CRP Hemoglobin White blood cell count Thrombocytes Liver function Kidney function Number of AE Patients preferences EQ5D Gutmicrobiota Questions on diet and alcohol consumption |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At each visit (after 0, 3, 6, 12 and 24 months) |
|
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 | No |
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 | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
peroral methotrexate is compared with subcutaneous methotrexate |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 12 |
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 | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |