KD025 in Subjects With Diffuse Cutaneous Systemic Sclerosis
This randomized, placebo-controlled phase 2 study is seeking to evaluate the efficacy and safety of belumosudil (KD025) for the treatment of diffuse cutaneous systematic sclerosis. Upon eligibility confirmation, a total of 60 adult subjects will be enrolled and randomized into 3 groups (1:1:1) to either receive orally administered belumosudil (200 mg once daily and 200 mg twice daily) or matched placebo for 28 weeks. Study drug dosing will be for 52 weeks: double-blinded for the first 28 weeks followed by an open-label extension of 24 weeks. After unblinding, the subjects on belumosudil will continue on the same belumosudil dose whereas the subjects in the placebo group will be re-randomized to one of the belumosudil doses.
- Male and female subjects ≥ 18 years old with the diagnosis of dcSSc according to the 2013 American College of Rheumatology and European League Against Rheumatism criteria
- Must have disease duration (defined as interval from first non-Raynaud disease manifestation) of ≤ 5 years
- Must have mRSS of ≥ 15 but ≤ 35
- Active disease defined as any of the following within the 6 months prior to screening:
- Increase in mRSS by ≥ 3 units
- Increase in mRSS by ≥ 2 units with involvement of 1 new body area
- Involvement of 2 new body areas
- Symptoms indicative of skin activity such as severe cutaneous itching or burning
- Subjects receiving concomitant immunosuppression must be on a stable dose for at least 3 months prior to screening
- Adequate organ and bone marrow functions evaluated during the 28 days prior to
enrollment as follows:
- Absolute neutrophil count ≥ 1.5 × 10^9/L
- Platelet count ≥ 100 × 10^9/L
- Total bilirubin ≤ 1.0 × upper limit of normal (ULN);
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine ≤ 1.5 × ULN.
- Female subjects of childbearing potential have a negative pregnancy test at screening.
Females of childbearing potential are defined as sexually mature women without prior
hysterectomy or who have had any evidence of menses in the past 12 months. However,
women who have been amenorrheic for 12 or more months are still considered to be of
childbearing potential if the amenorrhea is possibly due to prior chemotherapy,
anti-estrogens, or ovarian suppression.
- Women of childbearing potential (i.e., menstruating women) must have a negative urine pregnancy test (positive urine tests are 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 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 includes (1) intrauterine device plus 1 barrier method; (2) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus 1 barrier method; or (3) two 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 patients who are sexually active and who are partners of premenopausal women, agreement to use 2 forms of contraception as in Criterion Number 7 above during the treatment period and for at least 3 months after the last dose of study drug.
- Male subjects must not donate sperm for 3 months after last dose of study drug.
- Able to provide written informed consent prior to the performance of any study-specific procedures.
- Subject has corrected QT interval QTcF > 450 ms
- Ongoing use or current use of concomitant medication known to have the potential for QTc prolongation
- Female subject who is pregnant or breastfeeding
- 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)
- 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
- Chronic heart failure with New York Heart Association Class II, III, or IV
- Acute or chronic liver disease (e.g., cirrhosis)
- Positive human immunodeficiency virus (HIV) test
- Active hepatitis C virus (HCV), hepatitis B virus (HBV), or positive whole blood tuberculin test
- 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
- Has had previous exposure to belumosudil or known allergy/sensitivity to belumosudil, or any other ROCK2 inhibitor
- Scleroderma renal crisis within 4 months prior to enrollment
- FVC ≤ 50% Predicted.