A Study to Evaluate KD025 in Subjects with Diffuse Cutaneous Systemic Sclerosis

Overview

About this study

The purpose of this study is to evaluate the effectiveness and safety of KD025 in patients with diffuse cutaneous systemic sclerosis. Upon eligibility confirmation, a total of sixty (60) adult subjects will be enrolled and randomized into three (3) groups (1:1:1) to either receive orally administered KD025 (two doses) or matched placebo for 28 weeks. The study will be double-blinded for the first 28 weeks followed by an open label extension period of 24 weeks. After un-blinding, the subjects on KD025 will continue on the same KD025 dose whereas the subjects in the placebo group will be re-randomized to one of the KD025 doses.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male and female subjects ≥ 18 years old.
  • Diagnosis of dcSSc according to the 2013 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) 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) and aspartate aminotransferase (AST) within normal limits; 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 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:
      • IUD plus one barrier method;
      • on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; or
      • 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 patients who are sexually active and who are partners of premenopausal women: agreement to use 2 forms of contraception as in criterion 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.

Exclusion Criteria:

  • Subject has corrected QT interval using Fredericia’s formula (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 three 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 Classes 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Ashima Makol, M.B.B.S.

Closed for enrollment

More information

Publications

Publications are currently not available
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