Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  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: 1. Increase in mRSS by ≥ 3 units 2. Increase in mRSS by ≥ 2 units with involvement of one new body area 3. Involvement of two new body areas 4. Symptoms indicative of skin activity such as severe cutaneous itching or burning 5. Must be receiving a stable dose of mycophenolate mofetil (≤ 3 gm/day) or methotrexate (≤ 25 mg/week) for at least 4 weeks 6. Adequate organ and bone marrow functions evaluated during the twenty-eight (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) within normal limits; and 5. Serum creatinine ≤ 1.5 × ULN. 7. 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. 1. 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. 2. 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. 8. 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. 9. Male Subjects must not donate sperm for three (3) months after last dose of study drug. 10. Able to provide written informed consent prior to the performance of any study-specific procedures.

Exclusion Criteria

  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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Three (3) groups (1:1:1) to receive orally administered KD025 200 mg QD (n = 20), KD025 200 mg BID (n = 20), or matched placebo (n = 20) for twenty-eight (28) weeks. The study will be double-blinded for the first twenty-eight (28) weeks followed by an open-label extension of twenty-four (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 BID) in 1:1 fashion.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double-Blinded for the first 28 Weeks

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Group 1
20 subjects will be randomized to receive orally administered KD025 200 mg daily, double-blinded for the first 28 weeks. Subjects will then will be unblinded, and continue on the same KD025 dose for the remaining 24 weeks.
  • Drug: KD025
    ROCK-2 Inhibitor
  • Drug: Placebo
    Inactive substance
Experimental
Group 2
20 subjects will be randomized to receive orally administered KD025 200 mg twice a day, double-blinded for the first 28 weeks. Subjects will then will be unblinded, and continue on the same KD025 dose for the remaining 24 weeks.
  • Drug: KD025
    ROCK-2 Inhibitor
  • Drug: Placebo
    Inactive substance
Placebo Comparator
Group 3
20 subjects will be randomized to receive orally administered matched placebo, double-blinded for the first 28 weeks. Subjects will then will be unblinded, and re-randomized to one of the KD025 doses (200 mg daily or 200 twice a day) in a 1:1 fashion.
  • Drug: KD025
    ROCK-2 Inhibitor
  • Drug: Placebo
    Inactive substance

Recruiting Locations

Boston University
Boston, Massachusetts 02118
Contact:
Eric Stratton
617-358-6777
eas@bu.edu

More Details

Status
Recruiting
Sponsor
Kadmon Corporation, LLC

Study Contact

Nicholas Messier
724-778-6150
nicholas.messier@kadmon.com

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.