Moderate-to-Severe Plaque Psoriasis

Primary Assess whether BMS-986165 is superior to placebo at Week 16 in the treatment of subjects with moderate-to-severe plaque psoriasis Secondary and Additional Assess whether BMS-986165 is superior to placebo over the first 16 weeks of treatment Assess whether BMS-986165 is superior to placebo in scalp psoriasis through Week 16 in those subjects who have baseline scalp severity Physician’s Global Assessment (ss-PGA) score ≥3 Assess whether BMS-986165 is superior to placebo in nail psoriasis through Week 16 in those subjects who have baseline Physician’s Global Assessment of Fingernail Psoriasis(PGA-F)score ≥3

BMS-986165

BMS-986165

tablet

6

Primary Outcome Measures :

static Physician Global Assessment (sPGA) 0/1 response [ Time Frame: Baseline to Week 16 ]
Psoriasis Area and Severity Index (PASI) 75 response [ Time Frame: Baseline to Week 16 ]

1)Signed Written Informed Consent
a)Subjects must be willing to participate in the study and sign the informed consent form (ICF)
2)Type of Subject and Target Disease Characteristics
a)N/A
b)Deemed by the investigator to be eligible for phototherapy or systemic therapy
c)≥10% of BSA involvement at screening visit and Day 1
d)Psoriasis Area and Severity Index (PASI) score ≥12 and static Physician’s Global Assessment (sPGA) ≥3 at screening visit and Day 1
e)Men and women in mainland China, Taiwan, and South Korea diagnosed with stable plaque psoriasis for 6 months or more. Stable psoriasis is defined as no morphology changes or significant flares of disease activity in the opinion of the investigator
3)Age and Reproductive Status
a)Men and women aged ≥18 year sat the time of screening visit
b)Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening visit, and a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study drug
c)Women must not be pregnant, lactating, breastfeeding or planning pregnancy during the study period
d)Women of childbearing potential must agree to use correctly a highly effective method(s) of contraception for the duration of treatment (52 weeks) with study drug(s) BMS-986165 plus 5 half-lives of study drug (3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatment completion (total of 33 days after last dose of study drug). WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements, but must still undergo pregnancy testing as described in this protocol
e)Male subjects who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (APPENDIX 4 for the duration of treatment with study treatment(s) plus 5 half-lives of the study treatment (3 days) for a total of 3 days post-treatment completion. In addition, male subjects must be willing to refrain from sperm donation during this time

1)Target Disease Exceptions
a)Has nonplaque psoriasis (ie, guttate, inverse, pustular, erythrodermic or drug-induced psoriasis) at screening or Day 1
2)Infectious/Immune-related Exclusions
a)History or evidence of outpatient active infection and/or febrile illness within 7 days prior to Day 1
b)History of serious bacterial, fungal, or viral infection requiring hospitalization and intravenous (IV) antimicrobial treatment within 60 days prior to Day 1
c)Any untreated bacterial infection within 60 days prior to Day 1
d)Any ongoing evidence of chronic, bacterial infection (eg, chronic pyelonephritis, chronic osteomyelitis, chronic bronchiectasis) e)Any history of proven infection of a joint prosthesis in which the prosthesis was not removed or replaced, or received antibiotics for suspected infection of a joint prosthesis in which the prosthesis was not removed or replaced
f)Received live vaccines 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
g)Presence of herpes zoster lesions at screening or Day 1
h)History of serious herpes zoster or serious herpes simplex infection which includes, but is not limited to, any episode of disseminated herpes simplex, multidermatomal herpes zoster, herpes encephalitis, ophthalmic herpes, or recurrent herpes zoster (recurrent is defined as 2 episodes within 2 years)
i)Evidence of, or test positive for, hepatitis B virus (HBV) at Screening. Positive hepatitis B lab testing is defined as: 1) Positive hepatitis B surface antigen (HBsAg+) OR 2) Presence of hepatitis B virus deoxyribonucleic acid (DNA) OR 3) Positive anti-hepatitis B core antibody without concurrent positive hepatitis B surface antibody (HBcAb+ and HBsAb-)
j)Evidence of, or test positive for, hepatitis C virus (HCV) at screening. A positive test for HCV is defined as: 1) positive for hepatitis C antibody (anti-HCVAb) AND 2) positive via a confirmatory test for HCV (eg, HCV polymerase chain reaction)
k)Positive for human immunodeficiency virus by antibody testing (HIV-1 and -2 Ab) at screening
l)Any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the subject’s immune status (eg, history of opportunistic infections [eg,Pneumocystis jirovecii pneumonia, histoplasmosis, or coccidioidomycosis], history of splenectomy, primary immunodeficiency)
3)Any of the following tuberculosis (TB) criteria:
a)History of active TB prior to screening visit, regardless of completion of adequate treatment
b)Signs or symptoms of active TB (eg, fever, cough, night sweats, and weight loss) during screening as judged by the investigator c)Any imaging of the chest (eg, chest x-ray, chest computed tomography [CT] scan) obtained during the screening period or anytime within 6 months prior to screening with documentation, showing evidence of current active or history of active pulmonary TB
d)Latent TB infection (LTBI) defined as positive IFN gamma release assay (IGRA), by QuantiFERON-TB testing at screening, in the absence of clinical manifestations Note: Subject is eligible if (i) there are no current signs or symptoms of active TB AND(ii) subject has received adequate documented treatment for LTBI within 5 years of screening OR has initiated prophylactic treatment for LTBI per local guidelines and is rescreened after 1 month of treatment. To continue in the study, subject must agree to complete a locally-recommended course of treatment for LTBI.
4)Medical History and Concurrent Diseases
a)Any major surgery within 8 weeks prior to Day 1, or any planned surgery for the first 52 weeks of the study
b)Has donated blood >500 mL within 4 weeks prior to Day 1, or plans to donate blood during the course of the study
c)Illicit drug or alcohol abuse, as determined by the investigator, within 6 months prior to Day 1 (Note: medical marijuana is not allowed)
d)Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, psychiatric, neurologic, immunologic, or local active infection/infectious illness) that, in the investigator’s judgment or after consultation with the Medical Monitor, will substantially increase the risk to the subject if he or she participates in the study
e)Unstable cardiovascular disease, defined as a recent clinical cardiovascular event (eg, unstable angina, myocardial infarction, stroke, rapid atrial fibrillation) in the last 3 months prior to screening, or a cardiac hospitalization (e.g. revascularization procedure, pacemaker implantation) within 3 months prior to screening
f)Has uncontrolled arterial hypertension characterized by a systolic blood pressure (BP) >160 mm Hg or diastolic BP >100 mm Hg
g)Class III or IV congestive heart failure by New York Heart Association Criteria
h)Has cancer or history of cancer (solid organ or hematologic including myelodysplastic syndrome) or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma, or carcinoma of cervix in situ that has been treated with no evidence of recurrence)
i)Any significant/uncontrolled neuropsychiatric illness as clinically judged by the investigator during screening or at Day 1
j)Prior exposure to investigational product (ie, BMS-986165)
k)If the subject has received biologics previously, the following exclusion criteria for washout will apply: i)Antibodies to IL-12, IL-17 or IL-23 (eg, ustekinumab, secukinumab, tildrakizumab, ixekizumab, or guselkumab) within 6 months of Day 1 ii)TNF inhibitor(s) (e.g. etanercept, adalimumab, infliximab, certolizumab) within 2 months of Day 1 iii)Agents that modulate integrin pathways to impact lymphocyte trafficking (eg,natalizumab), or agents that modulate B cells or T cells (eg, alemtuzumab, abatacept, or visilizumab) within 3 months of Day 1 iv)Rituximab within 6 months of Day 1
l)Has received systemic non-biologic psoriasis medications and/or any systemic immunosuppressants (including, but not limited to, methotrexate, azathioprine, cyclosporine, JAK inhibitors, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus, oral or injectable corticosteroids, retinoids, 1,25-dihydroxy vitamin D3 and analogues, psoralens, sulfasalazine, or fumaric acid derivatives) within 4 weeks prior to Day 1
m)Has used leflunomide within 6 months prior to Day 1
n)Has used opioid analgesics within 4 weeks prior to Day 1
o)Has received lithium, antimalarials, or intramuscular (IM) gold within 4 weeks of the first administration of any study medication
p)Has received phototherapy (including either oral and topical PUVA light therapy, ultraviolet B [UVB] or self-treatment with tanning beds or therapeutic sunbathing) within 4 weeks prior to Day 1
q)Has used topical medications/treatments that could affect psoriasis evaluation (including, but not limited to, high potency corticosteroids (Classes I-V), >3% salicylic acid, urea, alpha- or beta-hydroxyl acids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens, pimecrolimus, and tacrolimus) within 2 weeks prior to Day 1
r)Use of shampoos that contain corticosteroids, coal tar, >3% salicylic acid, or vitamin D3 analogues within 2 weeks prior to Day 1
s)Has received an experimental antibody or experimental biologic therapy within the previous 6 months, OR received any other experimental therapy or new investigational agent within 30 days or 5 half-lives (whichever is longer) prior to Day 1 OR is currently enrolled in an investigational study
t)Any botanical preparations (eg, herbal supplements or traditional Chinese medicines derived from plants, minerals, or animals) intended to treat psoriasis or other immunological diseases within 4 weeks prior to Study Day 1
u)Any other sound medical, psychiatric and/or social reasons as determined by the investigator
5)Physical and Laboratory Evaluations a)At screening i)Absolute WBC count <3000/mm3ii)Absolute lymphocyte count <500/mm3iii)Absolute neutrophil count <1000/mm3iv)Platelet count <100,000/mm3v)Hemoglobin <9 g/dL vi)ALT and/or AST >3X upper limit of normal (ULN)vii) Total, unconjugated, and/or conjugated bilirubin >2 × ULN viii) Thyroid stimulating hormone (TSH) outside the normal range of 0.4 to 4.5 mIU/L b)ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the subject if participating in the study c)Renal impairment based on an estimated glomerular filtration rate (eGFR) <45 mL/min d)Positive urine drug screen during screening e)Inability to be venipunctured and/or tolerate venous access f)Any other significant laboratory abnormalities that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study
6)Allergies and Adverse Drug Reactions a)History of any significant drug allergy (such as anaphylaxis)
7)Other Exclusion Criteria a)Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and BMS approval is required). b)Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness c)Inability to comply with restrictions and prohibited activities/treatments as listed in the study protocol d)Site personnel or their immediate family