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 |
Rheumatoid Arthritis (RA) is an inflammatory disease that chiefly affects patients’ joints |
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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 | 16.0 |
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 primary objective is to assess the efficacy (as measured by the
reduction of the signs and symptoms of RA) of JNJ-38518168-ZBQ at doses of 3, 10, and 30 mg/d compared with placebo in subjects with active RA despite concomitant MTX therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
-To evaluate the safety and tolerability of JNJ-38518168-ZBQ -To characterize the population pharmacokinetics and exposure/response relationship of JNJ-38518168-ZBQ in adults with RA on a stable dose of MTX
Exploratory Objectives
The exploratory objectives are:
-To assess the effect of JNJ-38518168-ZBQ on health-related quality of life (HRQOL)
-To assess the effect of JNJ-38518168-ZBQ on various biomarkers |
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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 |
An optional intensive PK substudy will be conducted at selected sites in subjects who sign a separate consent form. Intensive PK blood samples will be collected within 7 days of the Week 4 visit pre-dose and at 2, 3, 4, 6, 8, and 10 hours post dose. |
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E.3 | Principal inclusion criteria |
Principal Inclusion Criteria in Lay Language (for a complete list of inclusion criteria refer to the protocol):
- Be a male or female between 18 and 80 years of age, inclusive.
- Have had a diagnosis of rheumatoid arthritis (RA) for at least 6 months before screening.
-Positive test for either anti-cyclic citrullinated peptide (anti-CCP) antibody or rheumatoid factor (RF) in serum at screening.
- Have active RA defined as persistent disease activity with the following criteria: at least 6 swollen and 6 tender joints at the time of screening and at baseline; and serum C-reactive protein >= 0.80 mg/dL at screening.
- Have been treated with, and tolerated methotrexate (MTX) at dosages from 10 to 25 mg/week, inclusive (6 to 16 mg/week, inclusive, for patients in Japan), for a minimum of 6 months prior to screening. Subjects must have a stable MTX dose for a minimum of 8 weeks prior to screening.
- Must be post-menopausal or if pre-menopausal, must use an acceptable form of birth control.
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E.4 | Principal exclusion criteria |
Principal Exclusion Criteria in Lay Language (for a complete list of exclusion criteria refer to the protocol):
- Have inflammatory diseases other than rheumatoid arthritis, such as Lupus
- Is currently receiving treatment for RA other than methotrexate, NSAIDS, corticosteroids (e.g. prednisone), or pain medicines.
- Have current signs or symptoms of liver or renal insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive, or uncontrolled.
- Have received biologic agent for rheumatic disease in the past
- Have a recent (2 months) serious infection
- Have an active infection
- Have had cancer within the past 5 years (except certain skin or cervical conditions)
- Have abused substances or alcohol within the past 2 years
– Have active Hepatitis B or C infection, or infective with HIV.
- Have had active tuberculosis.
- Have had exposure to tuberculosis without preventative treatment |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is change from baseline in Disease Activity Score DAS28 (CRP - C-reactive protein) at Week 12 |
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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) |
Secondary Efficacy Endpoints include:
1.Change from baseline in Disease Activity Score DAS28 (CRP - C-reactive protein) at Week 24.
2.Change from baseline in DAS28 (ESR - erythrocyte sedimentation rate) at Week 12 and Week 24
3.DAS28 (CRP) response rates at Week 12 and Week 24
4.DAS28 (ESR) response rates at Week 12 and Week 24
5.DAS28 (CRP) remission rates at Week 12 and Week 24
6.DAS28 (ESR) remission rates at Week 12 and Week 24
7.ACR20/50/70 (American College of Rheumatology) response rates at Week 12 and Week 24
8.Hybrid ACR response at Week 12 and Week 24
9.ACR/EULAR (European League Against Rheumatism) remission rates at Week 12 and Week 24
10.Change from baseline in Simplified Disease Activity Index SDAI at Week 12 and Week 24
11.Change from baseline in CDAI at Week 12 and Week 24
12.Health Assessment Questionnaire – Disability Index HAQ-DI response at Week 12 and Week 24
13.Change from baseline in HAQ-DI score at Week 12 and Week 24
14.Percent change from baseline in erythrocyte sedimentation rate
(ESR) levels at Week 12 and Week 24
15.Percent change from baseline in ACR components at Week 12 and Week 24 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.Week 24
2.Week 12 and Week 24
3.Week 12 and Week 24
4.Week 12 and Week 24
5.Week 12 and Week 24
6.Week 12 and Week 24
7.Week 12 and Week 24
8.Week 12 and Week 24
9.Week 12 and Week 24
10.Week 12 and Week 24
11.Week 12 and Week 24
12.Week 12 and Week 24
13.Week 12 and Week 24
14.Week 12 and Week 24
15.Week 12 and Week 24
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | 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.8.2.4 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Chile |
Colombia |
Czech Republic |
Hungary |
Japan |
Korea, Republic of |
Latvia |
Mexico |
Poland |
Romania |
Russian Federation |
Taiwan |
Thailand |
Ukraine |
United States |
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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 | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |