A Phase 2, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Belumosudil in Subjects With Moderate/Severe Chronic Plaque Psoriasis
Condition: Chronic Plaque Psoriasis
MeSH terms: Psoriasis
Intervention: Belumosudil; Placebo
Intervention description: Placebo tablets matching belumosudil
Intervention MeSH terms: Belumosudil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 110.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Skin Diseases; Auto-Immune Diseases; Plaque; Dermatology

Summary:

      This is a phase 2, randomized, placebo-controlled, 2-period study to evaluate the safety,
      tolerability, and efficacy of belumosudil in adult subjects with moderate to severe chronic
      plaque psoriasis who are candidates for systemic therapy or phototherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult subjects between the ages of 18 and 65 years

          -  Able to provide written Informed Consent Form prior to the performance of any
             study-specific procedures

          -  Diagnosis of moderate to severe chronic plaque psoriasis and a candidate for systemic
             therapy or phototherapy

          -  PASI of ≥ 12 at screening and prior to the first dose of study drug, confirmed at Week
             1 Day 1 (Baseline)

          -  ≥ 10% PASI body surface area involvement at screening and prior to the first dose of
             study drug, confirmed at Baseline

          -  Willing to avoid tanning devices

          -  Adequate bone marrow function:

               -  Absolute neutrophil count > 1500/mm^3

               -  Hemoglobin > 9.0 g/dL

               -  Platelets > 100,000/mm^3

          -  Adequate safety laboratory values:

               -  Serum total bilirubin within normal limits (WNL)

               -  Aspartate aminotransferase (AST) and alalnine aminotransferase (ALT) < 2 × upper
                  limit of normal (ULN)

               -  Serum creatinine < 1.5 × ULN

          -  Female subjects of childbearing potential with a negative pregnancy test at screening.
             Females of childbearing potential were defined as sexually mature women without prior
             hysterectomy or who had any evidence of menses in the past 12 months. However, women
             who had been amenorrheic for 12 or more months were still considered to be of
             childbearing potential if the amenorrhea was possibly due to prior chemotherapy,
             antiestrogens, or ovarian suppression

               -  Women of childbearing potential (i.e., menstruating women) had to have a negative
                  urine pregnancy test (positive urine tests were to be confirmed by serum test)
                  documented within the 24-hour period prior to the first dose of study drug

               -  Sexually active women of childbearing potential enrolled in the study had to
                  agree to use 2 forms of accepted methods of contraception during the course of
                  the study and for 3 months after their last dose of study drug. Effective birth
                  control included: (a) intrauterine device plus 1 barrier method; (b) on stable
                  doses of hormonal contraception for at least 3 months (e.g., oral, injectable,
                  implant, transdermal) plus one barrier method; and (c) 2 barrier methods.
                  Effective barrier methods were male or female condoms, diaphragms, and
                  spermicides (creams or gels that contained a chemical to kill sperm); or (d) a
                  vasectomized partner

          -  For male patients who were sexually active and who were partners of premenopausal
             women: agreed to use 2 forms of contraception as defined above during the treatment
             period and for at least 3 months after the last dose of study drug

          -  Willing to complete all study measurements and assessments in compliance with the
             protocol

        Exclusion Criteria:

          -  Non-plaque or drug-induced (antimalarials, lithium) psoriasis (If subject was taking
             angiotensin II receptor blockers or beta blockers doses must have been stable for 6
             months prior to study entry)

          -  Used systemic corticosteroids within 12 weeks prior to study entry

          -  Used topical corticosteroids except to the face, groin, or scalp

          -  Used methotrexate, retinoids (such as acitretin), or calcineurin inhibitors (such as
             cyclosporine) within 4 weeks prior to study entry

          -  Phototherapy within 4 weeks prior to study entry

          -  Biologic therapies, including antibodies to IL-17; anti-tumor necrosis factor-alpha;
             and anti-IL-12 & IL-23 within 3 months prior to study entry

          -  Current use of an inhibitor or inducer of CYP3A4

          -  Active viral, fungal, or bacterial skin infection (other than nail fungal infection).

          -  Pregnant or lactating woman

          -  History of gastrointestinal (GI) surgery including any bariatric surgery, or any GI
             condition that might interfere with drug absorption

          -  Participating in another study with an investigational drug or within 28 days or 5
             half-lives of the investigational drug (whichever was longer) of study entry

          -  History or other evidence of severe illness or any other conditions that would make
             the subject, in the opinion of the investigator, unsuitable for the study

          -  Regular and/or excessive use of alcohol within 2 years prior to study entry defined as
             alcohol intake > 14 drinks per week in a man or > 7 drinks per week in a woman.
             Approximately 10 g of alcohol equaled one "drink" unit. One unit equaled 1 ounce of
             distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine

          -  QT interval data corrected using Fridericia's formula (QTcF) > 450 msec (average of 3
             readings) during screening

          -  Exposure to belumosudil or known allergy/sensitivity to belumosudil within the last 6
             months prior to study entry or any other ROCK-2 inhibitor

          -  History or presence of any of the following:

               -  ALT or AST > 2.0 × ULN at screening

               -  Renal disease and/or serum creatinine > 1.5 × ULN at screening