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

• Status: Active, not recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is being conducted to evaluate the safety, tolerability, and activity of belumosudil (formerly known as KD025) in adult subjects with chronic Graft versus Host Disease (cGVHD).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kadmon Corporation, LLC

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 belumosudil or known allergy/sensitivity to belumosudil 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.