A Study to Evaluate the Safety, Tolerability, and Activity of KD025 in Subjects With Chronic Graft Versus Host Disease

• ClinicalTrials.gov Identifier: NCT02841995
• Recruitment Status: Active, not recruiting
• First Posted: July 22, 2016
• Last Update Posted: December 2, 2020
• Sponsor: Kadmon Corporation, LLC
• Information provided by (Responsible Party): Kadmon Corporation, LLC

Tracking Information

• First Submitted Date: July 20, 2016
• First Posted Date: July 22, 2016
• Last Update Posted Date: December 2, 2020
• Study Start Date: August 2016
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 4, 2018)

• Overall response criteria (PR + CR) [ Time Frame: Response assessment is measured at Day 1 of every cycle starting at Cycle 2 (ex: Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day 1, etc.). Cycle length is 28 days. ]
  To evaluate the overall response of KD025 200 mg QD, KD025 200 mg BID, or KD025 400 mg QD in subjects with cGVHD. The overall response will be evaluated through the NIH Consensus Development Project on Clinical Trials in cGVHD.
• Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From patient consent to 28 days post last KD025 dose. ]
  To evaluate the safety and tolerability of KD025 200 mg QD, KD025 200 mg BID, or KD025 400 mg QD when administered to subjects with cGVHD

Original Primary Outcome Measures (submitted: July 20, 2016)

• Overall response criteria (PR + CR) [ Time Frame: 24 weeks ]
  To evaluate overall response from baseline to 24 weeks after dosing with KD025 200 mg QD, KD025 200 mg BID, or KD025 400 mg QD in subjects with cGVHD. The overall response will be evaluated through the NIH Consensus Development Project on Clinical Trials in cGVHD.
• Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 24 weeks ]
  To evaluate the safety and tolerability of KD025 200 mg QD, KD025 200 mg BID, or KD025 400 mg QD when administered for 24 weeks to subjects with cGVHD

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety, Tolerability, and Activity of KD025 in Subjects With Chronic Graft Versus Host Disease
• Official Title: A Phase 2a, Dose-Escalation, Open-Label Study to Evaluate the Safety, Tolerability, and Activity of KD025 in Subjects With Chronic Graft Versus Host Disease
• Brief Summary: This study is being conducted to evaluate the safety, tolerability, and activity of KD025 in adult subjects with chronic Graft versus Host Disease (cGVHD).

Detailed Description

Approximately 48 subjects will be enrolled to receive orally administered KD025 200 mg QD (once daily), KD025 200 mg BID (twice daily), or KD025 400 mg QD. Once a recommended dose is chosen, approximately 40 additional subjects will be enrolled into the study at that dose.

Study drug will be administered in 28-day cycles until disease progression or unacceptable toxicity. Subjects may receive study drug in the inpatient or outpatient setting.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Graft vs Host Disease

Intervention

Drug: KD025

Other Name: SLx-2119

Study Arms

• Experimental: KD025 200 mg QD
  Two 100 mg capsules or one 200 mg tablet (200 mg) of KD025 once daily. Subjects should take 2 capsules or 1 tablet with their morning meal or within 5 minutes of completing a meal.
  Intervention: Drug: KD025
• Experimental: KD025 200 mg BID
  Two 100 mg capsules or one 200 mg tablet (200 mg) of KD025 twice daily. Subjects should take 2 capsules or 1 tablet with their morning meal or within 5 minutes of completing a meal and 2 capsules or 1 tablet with their evening meal or within 5 minutes of completing a meal.
  Intervention: Drug: KD025
• Experimental: KD025 400 mg QD
  Four 100 mg capsules or two 200 mg tablets (400 mg) of KD025 once daily. Subjects should take 4 capsules or 2 tablets with their morning meal or within 5 minutes of completing a meal.
  Intervention: Drug: KD025

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 4, 2018): 88
• Original Estimated Enrollment (submitted: July 20, 2016): 48
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult male and female subjects at least 18 years of age who have had allogenic bone marrow transplant (BMT) or hematopoietic stem cell transplantation (HSCT).
• Receiving glucocorticoid therapy and calcineurin therapy or glucocorticoid therapy alone for cGVHD at study entry. Subjects on calcineurin therapy only, without glucocorticoid therapy, are not eligible. Subjects also receiving other therapies thought not to be immunosuppressive (such as extracorporeal photopheresis; ECP), will be considered for enrollment in this study on a case-by-case basis.
• Have 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 > 40.

• Adequate organ and bone marrow functions evaluated during the 14 days prior to enrollment as follows:

  • Absolute neutrophil count ≥ 1.5 × 109/L (without myeloid growth factors within 1 week of study entry)
  • Platelet count ≥ 50 × 109/L (without transfusion or thrombopoietin or thrombopoietin analogues within 2 weeks of study entry)

• Adequate safety laboratory values:

  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
  • ALT and AST ≤ 3 × ULN
  • Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 using the MDRD-4 variable formula
• 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;
  • 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 patients who are sexually active and who are 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 subject who is pregnant or breastfeeding.
• Receiving an investigational GVHD treatment within 28 days of study entry.
• Has acute GVHD.
• Taking any medication known to be a moderate or strong inhibitor of the 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 subject, 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 g 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.
• Has had previous exposure to KD025 or known allergy/sensitivity to KD025 or any other ROCK-2 inhibitor.
• Taking other immunosuppressant drugs for GVHD, including mTor inhibitors (Note: Only steroids, calcineurin inhibitors, and ECP are acceptable).
• QTcF > 450 msec.1) Female subject who is pregnant or breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02841995
• Other Study ID Numbers: KD025-208
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Kadmon Corporation, LLC
• Study Sponsor: Kadmon Corporation, LLC
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Kadmon Corporation, LLC
• Verification Date: December 2020