Deucravacitinib (BMS-986165) for Pityriasis Rubra Pilaris

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed.

• Female and male patients ≥ 18 years of age.

• Subjects must have a diagnosis of PRP type 1, 2.

• Biopsy result consistent with PRP and not diagnostic for another disease.

• Moderate to severe disease defined as Psoriasis Area and Severity Index (PASI) ≥ 10.

• Candidates for systemic therapy.

• Inadequate response to or not suitable for topical therapy in the opinion of theinvestigator.

• If using any of the allowed topical treatments on the affected areas, the dose andapplication frequency should remain stable for 2 weeks prior to randomization anduntil Week 24.

Exclusion Criteria:

• On excluded therapies, not on a stable dose of a therapy, or incompletely washed outfor a therapy (Table-1.).

• Previous use of a TYK2 inhibitor/enrollment in TYK2 inhibitor trials.

• Known hypersensitivity or other adverse reaction to Deucravacitinib (BMS-986165).

• HIV related PRP (PRP type 6).

• atypical forms of PRP, e.g. presenting with ichtyosiform dermatitis, coarsepalmoplantar keratosis.

• Currently enrolled in any other clinical trial involving any investigational agentor device.

• Presence of any other skin condition that may affect the evaluations of the studydisease.

• Current, severe, progressive or uncontrolled diseases that render the patientunsuitable for the trial, including any medical or psychiatric condition that, inthe Investigator's opinion, would preclude the participant from adhering to theprotocol or completing the study per protocol.

• Ongoing use of ANY treatment prohibited by the protocol (Tables 1 & 2).

• Pregnant or nursing (lactating) women (pregnancy is defined as the state of a femaleafter conception and until the termination of gestation, confirmed by a positivehuman chorionic gonadotropin (hCG) laboratory test).

• Women of childbearing potential unless they are using basic methods of contraceptionwhich includes:

• Total abstinence when this is in line with the preferred and usual lifestyle ofthe patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods ofcontraception;

• Female sterilization (have had surgical bilateral oophorectomy [with or withouthysterectomy], total hysterectomy or tubal ligation at least six weeks beforetaking study; treatment). In case of oophorectomy alone, only when thereproductive status of the woman has been confirmed by follow-up hormone levelassessment;

• Male sterilization (at least 6 months prior to screening). The vasectomizedmale partner should be the sole partner for that patient;

• Barrier methods of contraception: Condom or Occlusive cap (diaphragm orcervical/vault caps);

• Use of oral (estrogen and progesterone), injected or implanted hormonal methodsof contraception or other forms of hormonal contraception that have comparableefficacy (failure rate < 1%), for example hormone vaginal ring or transdermalhormone contraception or placement of an intrauterine device (IUD) orintrauterine system (IUS). In case of use of oral contraception, women shouldhave been stable on the same pill for a minimum of 3 months before taking studytreatment.

• In case local regulations deviate from the contraception methods listed above,local regulations apply and will be described in the informed consent form (ICF).

• Note: Women are considered post-menopausal and not of childbearing potential ifthey have had 12 months of natural (spontaneous) amenorrhea with an appropriateclinical profile (e.g. age appropriate, history of vasomotor symptoms) or havehad surgical bilateral oophorectomy (with or without hysterectomy), totalhysterectomy or tubal ligation at least six weeks prior to enrollment. In thecase of oophorectomy alone, only when the reproductive status of the woman hasbeen confirmed by follow-up hormone level assessment is she considered not ofchildbearing potential.

• Underlying condition (including, but not limited to metabolic, hematologic, renal,hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinalconditions) which, in the opinion of the investigator, significantlyimmunocompromises the subject and/or places the subject at unacceptable risk forreceiving an immunomodulatory therapy.

• Moderate-to-severe renal impairment including patients with estimated glomerularfiltration rate (eGFR) < 60 mL/min/1.73m^2.

• Active systemic infections during the 2 weeks prior to randomization (common coldviruses excluded) or any infection that reoccurs on a regular basis.

• Current severe progressive or uncontrolled disease which the investigator rendersthe subject unsuitable for the trial or puts the subject at increased risk.

• Have had any major surgery within 8 weeks prior to screening or will require majorsurgery during the study that, in the opinion of the investigator would pose anunacceptable risk to the patient.

• Have experienced any of the following within 12 weeks of screening: VTE (DVT/pulmonary embolism [PE]), myocardial infarction (MI), unstable ischemic heartdisease, stroke, or New York Heart Association Stage III/IV heart failure.

• Have a history of recurrent (≥ 2) VTE (DVT/PE).

• Have a history of lymphoproliferative disease; have signs or symptoms suggestive ofpossible lymphoproliferative disease, including lymphadenopathy or splenomegaly;have active primary or recurrent malignant disease; or have been in remission fromclinically significant malignancy for < 5 years prior to randomization.

• Have had symptomatic herpes zoster infection within 12 weeks prior to randomization.

• Have a history of disseminated/complicated herpes zoster (for example, ophthalmiczoster or CNS involvement).

• ALT or AST > 2 x upper limits of normal (ULN); alkaline phosphatase (ALP) ≥ 2 x ULN;total bilirubin ≥ 1.5 x ULN; hemoglobin < 10 g/dL (100.0 g/L); total white bloodcell count < 3000 cells/μL (< 3.00 x 10^3/μL or < 3.00 billion/L); neutropenia (absolute neutrophil count [ANC] < 1500 cells/μL) (< 1.50 x 10^3/μL or < 1.50billion/L); lymphopenia (lymphocyte count < 1000 cells/μL) (< 1.00 x 10^3/μL or < 1.00 bilion/L); thrombocytopenia (platelets < 100,000 cells/μL) (< 100 x 10^3/μL or < 100 billion/L).

• Have a positive test for hepatitis B virus (HBV) defined as:

• Positive for hepatitis B surface antigen (HBsAg); or

• Positive for hepatitis B core antibody (HBcAb) and positive for hepatitis Bvirus deoxyribonucleic acid (HBV DNA) Note: Patients who are HBcAb-positive andHBV DNA-negative may be enrolled in the study but will require additional HBVDNA monitoring during the study.

• Have hepatitis C virus (HCV) infection (hepatitis C antibody-positive and HCVribonucleic acid [RNA]-positive). Note: Patients who have documented anti-HCVtreatment for a past HCV infection AND are HCV RNA-negative may be enrolled in thestudy.

• Have evidence of HIV infection and/or positive HIV antibodies.

• Have had household contact with a person with active TB and did not receiveappropriate and documented prophylaxis for TB.

• Have evidence of active TB or latent TB.

• Have evidence of active TB, defined in this study as the following:

• Positive purified protein derivative (PPD) test (≥ 5 mm induration betweenapproximately 2 and 3 days after application, regardless of vaccinationhistory), medical history, clinical features, and abnormal chest x-ray atscreening;

• QuantiFERON®-TB Gold test or T-SPOT®.TB test (as available and if compliantwith local TB guidelines) may be used instead of the PPD test. Patients areexcluded from the study if the test is not negative and there is clinicalevidence of active TB. Exception: patients with a history of active TB who havedocumented evidence of appropriate treatment, have no history of re-exposuresince their treatment was completed, have no clinical features of active TB,and have a screening chest x-ray with no evidence of active TB may be enrolledif other entry criteria met. Such patients would not be required to undergo theprotocol-specific TB testing for PPD, QuantiFERON®-TB Gold test, or T-SPOT®.TBtest but must have a chest x-ray at screening (i.e., chest imaging performedwithin the past 6 months will not be accepted).

• Have evidence of untreated/inadequately or inappropriately treated latent TB,defined in this study as the following:

• Positive PPD test, no clinical features consistent with active TB, and a chestx-ray with no evidence of active TB at screening; or

• If the PPD test is positive and the patient has no medical history or chestx-ray findings consistent with active TB, the patient may have aQuantiFERON®-TB Gold test or T-SPOT®.TB test (as available and if compliantwith local TB guidelines). If the test results are not negative, the patientwill be considered to have latent TB (for purposes of this study); or

• QuantiFERON®-TB Gold test or T- SPOT®.TB test (as available and if compliantwith local TB guidelines) may be used instead of the PPD test. If the testresults are positive, the patient will be considered to have latent TB. If thetest is not negative, the test may be repeated once within approximately 2weeks of the initial value. If the repeat test results are again not negative,the patient will be considered to have latent TB (for purposes of this study).

• Have been exposed to a live vaccine within 12 weeks of randomization or are expectedto need/receive a live vaccine during the course of the study (with the exception ofherpes zoster vaccination).

• Have donated more than a single unit of blood within 4 weeks prior to screening orintend to donate blood during the course of the study.

• Have a history of intravenous drug abuse, other illicit drug abuse, or chronicalcohol abuse within the 2 years prior to screening or are concurrently using, orexpected to use during the study, illicit drugs (including marijuana).