| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy |
|
| 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 |
| to assess the efficacy of golimumab in subjects with active RA despite MTX therapy as measured by the reduction of the signs and symptoms of RA at Week 14 and improvement in physical function at Week 24. |
|
| E.2.2 | Secondary objectives of the trial |
| to assess the safety, the effects of golimumab on structural damage and quality of life, and the population pharmacokinetics of golimumab in subjects with active RA despite MTX therapy. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Are women or men 18 years of age or older.
2. Have a diagnosis of RA for at least 3 months prior to screening.
3. Must have been treated with and tolerated MTX at a dose of at least 15 mg/week for at least 3 months prior to screening, and have a MTX dose of equal to or more than 15 mg/week and equal to or less than 25 mg/week and stable for at least 4 weeks prior to screening.
4. Have active RA as defined, for the purpose of this study, by persistent disease activity with at least 4 swollen and 4 tender joints, at the time of screening and at baseline and at least 2 of the following 4 criteria:
a. CRP equal to or more than 1.5 mg/dL at screening or ESR by Westergren method of equal to or greater than 28 mm in the first hour at screening or baseline.
b. Morning stiffness of equal to or more than 30 minutes at screening and baseline.
c. Bone erosion by x-ray and/or by MRI prior to the first administration of study agent.
d. Anti-cyclic citrullinated peptide (anti-CCP) antibody-positive or RF-positive at screening.
5. If using NSAIDs or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent.
6. If using oral corticosteroids, must be on a stable dose equivalent to equal to or less than 10 mg of prednisone/day for at least 2 weeks prior to first administration of study agent. If currently not using corticosteroids, the subject must have not received oral corticosteroids for at least 2 weeks prior to first administration of study agent.
7. Women of childbearing potential or men capable of fathering children must be using adequate birth control measures during the study and for 6 months after receiving the last administration of study agent.
Female subjects of childbearing potential must test negative for pregnancy.
8. Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB prior to screening.
b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
c. Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent.
d. Within 6 weeks prior to the first administration of study agent, either have negative diagnostic TB test results, or have a newly identified positive diagnostic TB test result during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent.
e. Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB.
9. Have screening laboratory test result as follows:
a. Hemoglobin equal to or more than 8.5 g/dL (International System of Units [SI]: equal to or more than 85 g/L) or equal to or more than 5.3 mmol/L.
b. WBC equal to or more than 3.5 x 10^3 cells/microL (SI: equal to or more than 3.5 x 10^9 cells/L).
c. Neutrophils equal to or more than 1.5 x 10^3 cells/microL (SI: equal to or more than 1.5 x 10^9 cells/L).
d. Platelets equal to or more than 100 x 10^3 cells/microL (SI: equal to or more than 100 x 10^9 cells/L).
e. Serum ALT and AST levels not exceeding 1.5 times the ULN for the central laboratory conducting the test.
f. Serum creatinine not exceeding 1.5 mg/dL (SI: equal to or less than 133 micromol/L).
10. Are willing and able to adhere to the study visit schedule and other protocol requirements.
11. Are capable of providing informed consent, which must be obtained prior to any study-related procedures. |
|
| E.4 | Principal exclusion criteria |
1. Have inflammatory diseases other than RA, including but not limited to PsA, AS, systemic lupus erythematosus, or Lyme disease, that might confound the evaluation of the benefit of golimumab therapy.
2. Have been treated with DMARDs/systemic immunosuppressives other than MTX during the 4 weeks prior to first administration of study agent.
3. Have received intra-articular, IM, or IV corticosteroids, including adrenocorticotropic hormone, during the 4 weeks prior to first administration of study agent.
4. Have a known hypersensitivity to human immunoglobulin proteins or other components of the golimumab.
5. Have received infliximab, etanercept, adalimumab, rituximab, or natalizumab.
6. Have received anakinra during the 4 weeks prior to first administration of study agent.
7. Have received alefacept or efalizumab within the 3 months prior to the first administration of the study agent.
8. Have used cytotoxic agents, including chlorambucil, cyclophosphamide, nitrogen
mustard, or other alkylating agents.
9. Have been treated with any investigational drug, including golimumab, within 5 half-lives of that drug prior to the first administration of study agent.
10. Are pregnant, nursing, or planning a pregnancy or fathering a child within 6 months after receiving the last administration of study agent.
11. Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening.
12. Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
13. Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB.
14. Have had a nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to screening.
15. Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months prior to the first administration of study agent, during the trial, or within 6 months after the last administration of study agent.
16. Have a history of an infected joint prosthesis, or have received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced.
17. Have had a serious infection, have been hospitalized for an infection, or have been treated with IV antibiotics for an infection within 2 months prior to first administration of study agent.
18. Have a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection, sinusitis, recurrent urinary tract infection, an open, draining, or infected skin wound, or an ulcer.
19. Are known to be infected with HIV, hepatitis B, or hepatitis C.
20. Have a history of known demyelinating diseases such as multiple sclerosis or optic neuritis.
21. Have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, psychiatric, or cerebral disease.
22. Have a history of, or concurrent, CHF, including medically controlled, asymptomatic CHF.
23. Have a history of lymphoproliferative disease, including lymphoma, or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location, or clinically significant splenomegaly.
24. Have any known malignancy or have a history of malignancy within the previous 5 years (with the exception of a nonmelanoma skin cancer that has been treated with no evidence of recurrence).
25. Have a transplanted organ.
26. Have or have had a substance abuse (drug or alcohol) problem within the previous 3 years.
27. Are unwilling or unable to undergo multiple venipunctures because of poor tolerability or lack of easy access.
28. Are participating in another trial with an investigational agent or procedure.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| ACR 20 response at Week 14 and change from baseline in health assessment questionnaire at Week 24. |
|
| 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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | 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 | 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 | 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 | 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 | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 75 |
| 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 |
|
| 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 | 5 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
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