A Study to Evaluate the Safety, Tolerability, and Activity of KD025 in Subjects With Chronic Graft Versus Host Disease
Condition: Graft vs Host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: Belumosudil (KD025)
Intervention description: Pharmaceutical form: Capsules or Tablets Route of administration: Oral
Intervention MeSH terms: Belumosudil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cGVHD; Allogeneic hematopoietic stem cell transplantation; Immune System Diseases; Steroid refractory chronic graft vs host disease (cGVHD); Bone Marrow Transplantation; Anti-Inflammatory Agents; Glucocorticoids; Corticosteroids

Summary:

      This study was been conducted to evaluate the safety, tolerability, and activity of
      belumosudil (formerly known as KD025) in adult participants with chronic graft versus host
      disease (cGVHD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult male and female participants at least 18 years of age who had allogenic bone
             marrow transplant (BMT) or hematopoietic stem cell transplantation (HSCT).

          -  Received glucocorticoid therapy and calcineurin therapy or glucocorticoid therapy
             alone for cGVHD at study entry. Participants on calcineurin therapy only, without
             glucocorticoid therapy, were not eligible. Participants also received other therapies
             thought not to be immunosuppressive (such as extracorporeal photopheresis; ECP), were
             considered for enrollment in this study on a case-by-case basis.

          -  Had persistent active cGVHD manifestations, as defined by 2014 NIH Consensus
             Development Project on Criteria for Clinical trials in cGVHD, after at least 2 months
             of steroid therapy.

          -  No more than 3 prior lines of treatment for cGVHD.

          -  Karnofsky Performance Scale of greater than (>) 40.

          -  Adequate organ and bone marrow functions evaluated during the 14 days prior to
             enrollment as follows:

               -  Absolute neutrophil count greater than or equal to (>=) 1.5*10^9/L (without
                  myeloid growth factors within 1 week of study entry)

               -  Platelet count >=50*10^9/L (without transfusion or thrombopoietin or
                  thrombopoietin analogues within 2 weeks of study entry)

          -  Adequate safety laboratory values:

               -  Total bilirubin less than or equal to (<=) 1.5*upper limit of normal (ULN)

               -  Alanine aminotransferase and aspartate aminotransferase <=3*ULN

               -  Glomerular filtration rate (GFR) >= 30 milliliter per minute per 1.73 square
                  meter (mL/min/1.73 m^2) using the 4-Variable Modification of Diet in Renal
                  Disease variable formula

          -  Female participants of childbearing potential have 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.

          -  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.

          -  Sexually active women of childbearing potential enrolled in the study must agree 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:

               -  Intrauterine device plus one barrier method;

               -  Stable doses of hormonal contraception for at least 3 months (e.g., oral,
                  injectable, implant, transdermal) plus one barrier method;

               -  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

          -  For male participants who were sexually active and who were partners of premenopausal
             women: agreement to use two forms of contraception as in criterion 10 above during the
             treatment period and for at least 3 months after the last dose of study drug.

          -  Able to provide written informed consent prior to the performance of any
             study-specific procedures.

        Exclusion Criteria:

          -  Female participant who was pregnant or breastfeeding.

          -  Received an investigational GVHD treatment within 28 days of study entry.

          -  Had acute GVHD.

          -  Taken any medication known to be a moderate or strong inhibitor of the cytochrome (CY)
             CYP3A4 isozyme or any drugs that are moderate or strong CYP3A4 inducers.

          -  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 (such as
             poorly controlled psychiatric disease or coronary artery disease).

          -  Regular and excessive use of alcohol within the 6 months 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 grams of alcohol equals one "drink" unit. One unit equals 1 ounce of
             distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine.

          -  Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV)
             or hepatitis B virus (HBV).

          -  Diagnosed with another malignancy (other than malignancy for which transplant was
             performed) within 3 years of enrollment, with the exception of completely resected
             basal cell or 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.

          -  Relapse of the underlying cancer or post-transplant lymphoproliferative disease at the
             time of screening.

          -  Had previous exposure to belumosudil or known allergy/sensitivity to belumosudil or
             any other Rho-associated protein kinase-2 inhibitor.

          -  Taken other immunosuppressant drugs for GVHD, including mammalian target of rapamycin
             inhibitors (Note: Only steroids, calcineurin inhibitors, and ECP are acceptable).

          -  Corrected QT interval using Fridericia's formula >450 milliseconds.

          -  Female participant who was pregnant or breastfeeding.