Efficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis
Condition: Diffuse Cutaneous Systemic Sclerosis
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis
Intervention: Belumosudil
Intervention description: 10 participants with dcSSc received belumosudil 200 mg PO BID for 52 weeks
Intervention MeSH terms: Belumosudil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Belumosudil 200 mg PO BID
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: skin diseases; systemic sclerosis; phase 2; Scleroderma Health Assessment Questionnaire Disability Index; Modified Rodnan Skin Score; Combined Response Index in dcSSc (CRISS); diffuse cutaneous systemic sclerosis

Summary:

      This was a phase 2, open-label, single-cohort, multicenter trial of belumosudil in
      participants with Diffuse Cutaneous Systemic Sclerosis (dcSSc). An estimated total of 12 to
      15 participants would receive belumosudil 200 milligrams (mg) administered orally (PO) twice
      daily (BID) for 52 weeks. The primary analysis was at 24 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female participants greater than or equal to (>=) 18 years old with the
             diagnosis of dcSSc according to the 2013 American College of Rheumatology and European
             League Against Rheumatism.

          2. Had disease duration (defined as interval from first non Raynaud disease
             manifestation) of less than or equal to (<=) 6 years.

          3. Had mRSS of >=15 but <=40.

          4. Had active disease as determined by the Principal Investigator within the 6 months
             prior to screening.

          5. Adequate organ and bone marrow functions evaluated during the 28 days prior to
             enrollment as follows:

               1. Absolute neutrophil count >= 1.5*10^9/L

               2. Platelet count >= 100*10^9/L

               3. Total bilirubin <= 1.0*upper limit of normal (ULN)

               4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and serum
                  creatinine <= 1.5*ULN.

          6. Female participants of childbearing potential had 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,
             anti-estrogens, or ovarian suppression.

               1. Women of childbearing potential (i.e., menstruating women) must had 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.

               2. Sexually active women of childbearing potential enrolled in the study agreed to
                  use two 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
                  includes (i) intrauterine device plus 1 barrier method; (ii) on stable doses of
                  hormonal contraception for at least 3 months (e.g., oral, injectable, implant,
                  transdermal) plus 1 barrier method; or (iii) 2 barrier methods. Effective barrier
                  methods are male or female condoms, diaphragms, and spermicides (creams or gels
                  that contain a chemical to kill sperm), or a vasectomized partner.

          7. For male participants who were sexually active and who were partners of premenopausal
             women: agreement to use 2 forms of contraception as in criterion number 6b above
             during the treatment period and for at least 3 months after the last dose of study
             drug.

          8. Male participants must not donate sperm for 3 months after last dose of study drug.

          9. Able to provide written informed consent prior to the performance of any
             study-specific procedures.

        Exclusion Criteria:

          1. Participants had corrected QT interval using Fridericia's formula (QTcF) greater than
             450 milliseconds.

          2. Ongoing use or current use of concomitant medication known to have the potential for
             QTc prolongation.

          3. Female participant who was pregnant or breastfed.

          4. Participated in another study with an investigational drug within 28 days of study
             entry (for studies involving biologics, within 3 half-lives of the biologic).

          5. History or other evidence of severe illness or any other conditions that would make
             the participant, in the opinion of the Investigator, unsuitable for the study.

          6. Chronic heart failure with New York Heart Association Classes II, III, or IV.

          7. Acute or chronic liver disease (e.g., cirrhosis).

          8. Positive human immunodeficiency virus (HIV) test.

          9. Active hepatitis C virus (HCV), hepatitis B virus (HBV), or positive whole blood
             tuberculin test.

         10. Diagnosed with any malignancy within 3 years of enrollment, with the exception of
             basal cell or completely resected squamous cell carcinoma of the skin, resected in
             situ cervical malignancy, resected breast ductal carcinoma in situ, or low risk
             prostate cancer after curative resection.

         11. Had previous exposure to belumosudil or known allergy/sensitivity to belumosudil, or
             any other Rho-associated Protein Kinase-2 (ROCK2) inhibitor.

         12. Scleroderma renal crisis within 4 months prior to enrollment.

         13. Forced vital capacity <= 50% Predicted.