E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Rheumatoid Arthritis with an Inadequate Response to Methotrexate With or Without TNF Inhibitors |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 20.0 |
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 |
|
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 purpose of this study is to determine whether the study drug, BMS-986142, is safe and effective in treating moderate to severe rhematoid arthritis in subjects with an inadequate response to methotrexate or methotrexate and up to 2 TNF Inhibitors. Patients who qualify will be randomized to either one of 3 doses of BMS-986142 or placebo in 1:1:1:1 randomization for 12 weeks. Disease activity and safety will be assessed over the course of the study. |
|
E.2.2 | Secondary objectives of the trial |
1) Assess additional efficacy outcomes of BMS-986142 at Week 12 and over 12 weeks of treatment as measured by ACR20, ACR50 and ACR70 response rates, DAS28-CRP change from baseline, DAS28-ESR change from baseline, Clinical Disease Activity Index ( CDAI), Simplified Disease Index (SDAI), and Boolean remission.
2) Assess the safety and tolerability of BMS-986142.
3) Evaluate pre-dose concentration (Ctrough) of BMS-986142.
4) Assess the efficacy of BMS-986142+MTX to -MTX in reducing synovitis, osteitis, bone erosions, and cartilage loss in hands/wrists by MRI at Weeks 4, and 12 from baseline. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female age 18 and above
- Diagnosed with active rheumatoid arthritis (RA) by standard criteria at least 16 weeks before screening, have functional ACR class I-III
- Have an inadequate response to methotrexate
- In addition to an inadequate response to methotrexate have an inadequate response or intolerance to 1 but not more than 2 TNF inhibiotrs
- Have a minimum of 6 swollen and 6 tender joints (from 66/68 joint count)
- Have hsCRP of ≥ 0.8 mg/dL (8mg/L) [by central laboratory values] or an ESR ≥ 28 mm/hr
- Willing to use effective birth control for the entire length of the study |
|
E.4 | Principal exclusion criteria |
- Diagnosed with juvenile Rheumatoid Arthritis
- Have been treated with other biologic treatment than a TNF inhibitor
- Active systemic bacterial, viral or fungal infection or evidence of prior or current Hepatitis B or C infection or HIV infection, latent bacterial, viral or fungal infections
- Have been treated with Intramuscular or Intra-articular glucocorticosteroids within 4 weeks of randomization
- Taking Oral steroids at dose above 10 mg/day of prednisone (or prednisone equivalents)
- Have other autoimmune disease other than RA like lupus, multiple sclerosis
- Have significant concurrent medical condition at the time of screening or baseline visit
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Co-Primary:
- Proportion of subjects who achieve ACR70 response rate at Week 12
- Proportion of subjects who achieve ACR20 response rate at Week 12
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1/ Proportion of subjects who achieve ACR20, ACR50, ACR70
2/ Proportion of subjects who achieve DAS28-CRP < 2.6
3/ Proportion of subjects who achieve DAS28-ESR < 2.6
4/ Proportion of subjects who achieve CDAI ≤ 2.8
5/ Proportion of subjects who achieve SDAI ≤ 3.3
6/ Proportion of subjects who achieve Boolean Remission
7/ Change from baseline in DAS28-CRP score, DAS28-ESR score
8/ Change from baseline in CDAI score, SDAI score
9/ Change from baseline in RAMRIS scores of synovitis, osteitis (bone marrow edema), bone erosion and cartilage loss (joint-space narrowing) (MRI)
10/ Incidence and severity of all Adverse Events (AEs), Serious AEs, and pre-established Events of Special Interest, clinically significant changes in vital signs, clinically significant ECG abnormalities, clinically significant abnormalities in general laboratory tests
11/ Plasma concentration of BMS-986142
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ to 6/ over time from baseline to Week 12
7/ and 8/ over time up to Week 12
9/ to Week 4, and Week 12
10/ During study
11/ Predose at specified time points
|
|
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 | Yes |
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 | 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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Austria |
Belgium |
Brazil |
Canada |
France |
Germany |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Russian Federation |
South Africa |
Spain |
Taiwan |
United States |
|
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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 22 |