| 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 |
| Psoriatic arthritis (PsA) is a chronic inflammatory disease |
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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 | 20.0 |
| 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 |
| Assess the dose-response relationship of BMS-986165 (6 or 12 mg once daily [QD]) at Week 16 in the treatment of subjects with active PsA |
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| E.2.2 | Secondary objectives of the trial |
Assess the dose-response relationship of BMS-986165 (6 or 12 mg QD) at Week 16 in daily functional activities
Assess the dose-response relationship of BMS-986165 (6 or 12 mg QD) at Week 16 in reducing PSO severity
Assess the dose-response relationship of BMS-986165 (6 or 12 mg QD) at Week 16 in Patient-reported Outcomes
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Signed Written Informed Consent
2.Type of Participant and Target Disease Characteristics
Diagnosed with PsA for at least 6 months before screening, and who meet the Classification Criteria for Psoriatic Arthritis (CASPAR) at screening.
Subjects either (i) cannot have prior exposure to biologics (biologic-naïve) or (ii) have failed or been intolerant to 1 TNF-inhibitor (TNFi-experienced). Failure is defined as lack of response or loss of response with at least 3 months of therapy with an approved dose of a TNFi, as judged by the investigator. Failure must have occurred at least 2 months prior to Day 1.
Subjects have at least 1 confirmed ≥ 2 cm lesion of plaque psoriasis at screening.
Subjects have active arthritis as shown by a minimum of ≥ 3 swollen joints and ≥ 3 tender joints (66/68 joint counts) at screening and Day 1.
High sensitivity C-reactive protein (hsCRP) ≥ 3mg/L at screening.
If on a conventional non-biologic DMARD (eg MTX, leflunomide, sulfasalazine or hydroxychloroquine) subjects can only take 1 DMARD. The DMARD must have been used for at least 3 months with a stable dose for at least 28 days prior to Day 1.
Have failed or been intolerant to at least 1 non-biologic DMARD (or had to stop because of pregnancy or lactation but still eligible for the trial), NSAID and/or corticosteroid.
If using an NSAID, the dose must be stable for at least 14 days before Day 1 and consistent with labeling recommendations.
If using oral corticosteroids (≤ 10 mg/day prednisone equivalent), the dose must be stable for at least 14 days before Day 1.
Concurrent topical therapy for plaque psoriasis must have been stable for at least 14 days before Day 1.
3.Age and Reproductive Status
Men and women aged ≥18 years at screening.
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment.
Women must not be pregnant, lactating, breastfeeding or be planning pregnancy during the study period.
Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) post-treatment completion. Therefore in Part A WOCBP must agree to follow instructions for methods of contraception for 33 days post-treament completion while in Part B WOCBP must agree to follow instructions for methods of contraception for 190 days post-treatment completion.
Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment plus 5 half-lives of the study treatment plus 90 days post-treatment completion Therefore in Part A, males who are sexually active with WOCBP must agree to follow instructions for methods of contraception for 93 days post-treatment completion, while in Part B males must agree to follow instructions for methods of contraception for 250 days post-treatment completion.
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| E.4 | Principal exclusion criteria |
| 1.Target Disease Exceptions.Has non-plaque psoriasis at screening or Day 1.Has any other autoimmune condition such as rheumatoid arthritis.Has active fibromyalgia.2.Infectious/Immune-related.History or evidence of active infection and/or febrile illness within 7 days prior to Day 1. History of recent serious bacterial, fungal, or viral infections requiring hospitalization and intravenous antimicrobial treatment within 90 days prior to screening, or any infection requiring antimicrobial treatment within 15 days prior to Day 1.Any bacterial infection within the last 60 days prior to screening, unless treated and resolved with antibiotics, or any chronic bacterial infection.Received live vaccine(s) within 60 days prior to Day 1, or plans to receive a live vaccine during the study, or within 60 days after completing study treatment.Presence of herpes simplex lesions or herpes zoster at screening or Day 1.History of severe herpes zoster or severe herpes simplex infection.Evidence of, or test positive for, hepatitis B.Evidence of, or test positive for, hepatitis C virus. Positive for human immunodeficiency virus antibody at screening.Any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the subject’s immune status.3.Any of the following tuberculosis criteria:History of active TB prior to screening visit, regardless of completion of adequate treatment.Signs or symptoms of active TB during screening.Any imaging of the chest obtained during the screening period, or anytime within 6 months prior to Screening with documentation, showing evidence of current active or old pulmonary TB.Latent TB infection defined as positive IFN gamma release assay, by QuantiFERON-TB Gold testing at screening, in the absence of clinical manifestations.4.Medical History and Concurrent Diseases.If the subject is biologic-experienced, the following exclusion criteria will apply:History of use of antibodies to IL-12, IL-17, or IL-23.TNF-inhibitor(s) within 2 months of Day 1.History of use of agents that modulate lymphocyte trafficking, or agents that modulate B cells or T cells. If the subject is biologic-naïve: has not received any biologic immunomodulatory treatment.Any major surgery within 4 weeks prior to Day 1, or any planned surgery for the first 52 weeks of the study.Has donated blood > 500 mL within 4 weeks prior to Day 1, or intends to donate blood during the course of the study. Drug or alcohol abuse within 6 months prior to Day 1. Any major illness/condition or evidence of an unstable clinical condition that will substantially increase the risk to the subject if he or she participates in the study.Unstable cardiovascular disease, defined as a recent clinical deterioration in the last 3 months prior to screening, or a cardiac hospitalization within the 3 months prior to screening.Has uncontrolled arterial hypertension characterized by a systolic blood pressure > 160 mm Hg or diastolic BP > 100 mm Hg. Class III or IV congestive heart failure by New York Heart Association Criteria.History of cancer or lymphoproliferative disease within the previous 5 years.Any other sound medical, and/or social reason.Prior exposure to the investigational product.Has received any JAK inhibitors.Has received systemic non-biologic psoriasis medications and/or any systemic immunosuppressants therapy within 4 weeks prior to Day 1.Use of any opioid analgesic at average daily doses of > 30 mg/day of morphine or its equivalent or use of variable doses of any opiate analgesic within 6 weeks prior to Day 1.Has received phototherapy within 4 weeks prior to Day 1.Has used topical medications/treatments that could affect psoriasis evaluation within 2 weeks of Day 1.Use of shampoos that contain corticosteroids, coal tar, or vitamin D3 analogues within 2 weeks prior to Day 1.Has received any experimental therapy or new investigational agent within 30 days or 5 half-lives prior to Day 1 or is currently enrolled in an investigational study.5.Physical and Laboratory Test Findings.Absolute white blood cell (WBC) count < 3000/mm3 at screening.Absolute lymphocyte count < 500/mm3 at screening.Absolute neutrophil count < 1000/mm3 at screening.Platelet count < 100,000/mm3 at screening.Hemoglobin < 9 g/dL at screening.ALT and/or AST > 2x upperlimit of normal (ULN) at screening.Total, unconjugated, and/or conjugated bilirubin > 1.5x ULN at screening, except for any subject with a diagnosis of Gilbert’s syndrome.Estimated glomelular filtration rate (eGFR) < 45 mL/min .Any other significant laboratory or procedure abnormalities might place the subject at unacceptable risk for participation in this study. 2)Allergies and Adverse Drug Reactions.3.Other Exclusion Criteria. Prisoners. Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.Inability to comply with restrictions and prohibited activities/treatments Site personnel or their immediate family |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
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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) |
Change from baseline in HAQ-DI score
PASI 75 response
Change from baseline in the Physical Component Summary (PCS) score of the SF-36 Questionnaire
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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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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 | 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 | Yes |
| E.8.2.3.1 | Comparator description |
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| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 66 |
| 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 |
| Belgium |
| Czech Republic |
| Germany |
| Hungary |
| Italy |
| Poland |
| Russian Federation |
| Spain |
| United Kingdom |
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| 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 |
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