Summary

for people ages 18-100 (full criteria)
at La Jolla, California and other locations
study started
estimated completion
Arthur Kavanaugh, MD

Description

Summary

Phase II Diffuse Cutaneous Systemic Sclerosis study seeking to evaluate the efficacy and safety of KD025. 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.

Official Title

A Phase 2, Randomized, Placebo-controlled, Double-blind, Open-label Extension Multicenter Study to Evaluate the Efficacy and Safety of KD025 in Subjects With Diffuse Cutaneous Systemic Sclerosis

Details

Systemic sclerosis (SSc) is a chronic autoimmune disease that causes widespread microvascular damage and excessive deposition of collagen in the skin and internal organs. Limited cutaneous systemic sclerosis is primarily cutaneous, affecting the hands, arms, and face. Diffuse cutaneous systemic sclerosis (dcSSc) is a more serious manifestation of the disease and is often rapidly progressive, not only involving the skin, but also involving internal organs including kidney, heart, and lungs.

Subjects who have signed an IRB/IEC-approved informed consent form and met all of the inclusion/exclusion criteria will be enrolled. A total of sixty (60) subjects will be randomized into three (3) groups (1:1:1) to receive orally administered KD025 200 mg once daily (QD; n = 20), KD025 200 mg twice daily (BID; n = 20), or matched placebo (n = 20) for 28 weeks. The study will be double-blinded for the first 28 weeks followed by an open-label extension of 24 weeks. After unblinding, the subjects in Group 1 and 2 will continue on the same KD025 dose whereas the subjects in the placebo group will be re-randomized to one of the KD025 doses (200 mg QD or 200 mg BID) in 1:1 fashion.

Keywords

System; Sclerosis Diffuse Cutaneous Systemic Sclerosis Scleroderma, Systemic Scleroderma, Diffuse Sclerosis

Eligibility

You can join if…

Open to people ages 18-100

  1. Male and female subjects ≥ 18 years old with the diagnosis of dcSSc according to the 2013 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria
  2. Must have disease duration (defined as interval from first non-Raynaud disease manifestation) of ≤ 5 years
  3. Must have mRSS of ≥ 15 but ≤ 35
  4. Active disease defined as any of the following within the 6 months prior to screening:
  5. Increase in mRSS by ≥ 3 units
  6. Increase in mRSS by ≥ 2 units with involvement of one new body area
  7. Involvement of two new body areas
  8. Symptoms indicative of skin activity such as severe cutaneous itching or burning
  9. Must be receiving a stable dose of mycophenolate mofetil (≤ 3 gm/day) or methotrexate (≤ 25 mg/week) for at least 4 weeks
  10. Adequate organ and bone marrow functions evaluated during the twenty-eight (28) days prior to enrollment as follows:
  11. Absolute neutrophil count ≥ 1.5 × 109/L

  12. Platelet count ≥ 100 × 109/L

  13. Total bilirubin ≤ 1.0 × upper limit of normal (ULN);
  14. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal limits; and
  15. Serum creatinine ≤ 1.5 × ULN.
  16. 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 twelve (12) months. However, women who have been amenorrheic for twelve (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.
  17. 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.
  18. 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 three (3) months after their last dose of study drug. Effective birth control includes (i) IUD plus one barrier method; (ii) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; or (iii) 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.
  19. For male patients who are sexually active and who are partners of premenopausal women: agreement to use two (2) forms of contraception as in criterion number 7 above during the treatment period and for at least three (3) months after the last dose of study drug.
  20. Male Subjects must not donate sperm for three (3) months after last dose of study drug.
  21. . Able to provide written informed consent prior to the performance of any study-specific procedures.

You CAN'T join if...

  1. Subject has QTcF >450 ms
  2. Female subject who is pregnant or breastfeeding;
  3. Participated in another study with an investigational drug within twenty-eight (28) days of study entry (for studies involving biologics, within three half-lives of the biologic);
  4. 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;
  5. Chronic heart failure with New York Heart Association Class II,III or IV;
  6. Positive human immunodeficiency virus (HIV) test;
  7. Active hepatitis C virus (HCV), hepatitis B virus (HBV), or positive tuberculin skin test;
  8. Diagnosed with any malignancy within three (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;
  9. Has had previous exposure to KD025 or known allergy/sensitivity to KD025, or any other ROCK2 inhibitor;
  10. . Scleroderma renal crisis within four (4) months prior to enrollment;
  11. . FVC ≤ 50%. Predicted.

Locations

  • University of California - San Diego not yet accepting patients
    La Jolla California 92037 United States
  • University of California - Los Angeles not yet accepting patients
    Los Angeles California 90095 United States

Lead Scientist

  • Arthur Kavanaugh, MD
    Research Interests Innovative strategies for the treatment of patients with rheumatoid arthritis and other rheumatic diseases. Prognostic and predictive factors for outcomes in rheumatic diseases. Research program on innovative approaches to various immunologic diseases, particularly novel biologic therapies.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Kadmon Corporation, LLC
ID
NCT03919799
Phase
Phase 2
Study Type
Interventional
Last Updated