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] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
E.1.2 | System Organ Class | 100000004859 |
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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 purpose of this study is to characterize the safety, efficacy and dose response of BMS-945429 in subjects with active Psoriatic Arthritis and an inadequate response to NSAIDs and non-biologic DMARDs |
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E.2.2 | Secondary objectives of the trial |
1) Proportion of subjects achieving PASI 75 response rate at Weeks 16 and 24
2) Proportion of subjects achieving ACR50 and ACR70 response rate at Weeks 16 and 24
3) Proportion of subjects achieving ACR20 response rate at Week 24
4) Proportion of subjects achieving a HAQ response at Weeks 16 and 24, as measured by a reduction of at least 0.3 unit from baseline in HAQ index
5) SF-36 changes from baseline to Weeks 16 and 24
6) AEs, vital signs, physical examinations, safety lab values, and immunogenicity during double-blind period |
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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 |
Skin Biopsy Substudy (see section 5.4.4.9 of the protocol):
Skin biopsy is a standard diagnostic test performed for skin diseases, and has been used to characterize responses to therapeutic agents in patients diagnosed with psoriasis and
psoriatic arthritis. Subjects from selected sites will enroll in the skin biopsy substudy. For additional details, refer to the protocol.
Intensive PK Sub study (see section 5.5.1 of the protocol):
Approximately the first 32 subjects randomized will have blood samples collected for a full profile PK analysis over the dosing intervals from Week 20 to Week 24. For these subjects, in addition to obtaining a same sparse PK schedule as standard PK
sampling , additional PK samples will be collected on Week 20 + 3 day, Week 20 + 5 day, Week 21, Week 22, and Week 23. For additional details, refer to the protocol.
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E.3 | Principal inclusion criteria |
• Must be on a stable background methotrexate (MTX) therapy prior to Day1/Randomization. Subjects must have taken MTX for at least 3 months at a dose ≥ 15 mg to a maximum weekly dose of ≤ 25 mg, and be at a stable dose for 4 weeks prior to enrollment. Methotrexate dose ≤ 15 mg/week that was not efficacious and that was decreased due to toxicity as low as 10 mg/week is allowed.
• Inadequate response to NSAID or non-biologic DMARD
• Minimum of 3 swollen and 3 tender joints
• Active psoriatic skin lesions over minimum 3% body surface area
• hsCRP ≥ 0.3 mg/dL
• Subjects must have diagnosis of active PsA by Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 12 weeks prior to screening
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E.4 | Principal exclusion criteria |
• Previously received or currently receiving concomitant biologic therapy |
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E.5 End points |
E.5.1 | Primary end point(s) |
American College of Rheumatology criteria (ACR20) |
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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) |
1) Proportion of subjects achieving PASI 75 response rate
2) Proportion of subjects achieving ACR50 and ACR70 response rate
3) Proportion of subjects achieving ACR20 response rate
4) Mean change from baseline in Health Assessment Questionnaire (HAQ) Index
5) Proportion of subjects achieving a HAQ response, as measured by a reduction of at least 0.3 unit from baseline in HAQ index
6) SF-36 changes from baseline
7) AEs, vital signs, safety lab values, and immunogenicity during double-blind period |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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
| 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 | 2 |
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 |
Australia |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Mexico |
Poland |
Russian Federation |
South Africa |
Spain |
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 | 2 |
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 | 2 |
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 |