Efficacy and Safety of KD025 in Subjects With cGVHD After At Least 2 Prior Lines of Systemic Therapy

Investigational Treatment for Chronic Graft Versus Host Disease (cGVHD) After Multiple Therapies

Not Recruiting
12 years or above
All
Phase 2
159 participants needed

Study Overview

This is a Phase 2, randomized, multicenter study to evaluate the efficacy and safety of KD025 in subjects with Chronic Graft Versus Host Disease (cGVHD) after at least 2 prior lines of systemic therapy

Study Details

Phase 2, open label, randomized, multicenter study in subjects with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy. Approximately 166 subjects with active cGVHD will be randomized (1:1) to receive treatment with one of two belumosudil (formerly known as KD025) regimens:

  • Arm A: belumosudil 200 mg QD
  • Arm B: belumosudil 200 mg BID

With Amendment 2, the sample size was increased from approximately 126 subjects, with additional subjects to be enrolled as follows:

  • 20 adolescents
  • 20 adults into a site-specific Companion Study to collect biospecimens

These additional subjects will also be randomized (1:1) to Arm A or Arm B.

Any adolescent taking a proton pump inhibitor (PPI) or a strong CYP3A4 inducer will begin Cycle 1 Day 1 at the escalated dose of belumosudil 200 mg BID.

Randomization will be stratified according to prior cGVHD treatment with ibrutinib (Yes / No) and severe cGVHD at baseline (Yes / No). Subjects may receive treatment in 28-day treatment cycles until clinically significant progression of cGVHD. Subjects who have not achieved a response after 12 cycles of belumosudil should be withdrawn if in the Investigator's judgment there is no evidence of clinical benefit. Subjects will undergo evaluations as outlined in the Study Assessments table (Appendix A). The primary endpoint is the overall response rate (ORR) with responses as defined by the 2014 National Institute of Health (NIH) Consensus Development Project on clinical trials in cGVHD.

Eligibility Criteria

You may be eligible for this study if you meet the following criteria:

  • Conditions: Chronic Graft-versus-host-disease
  • Age: 12 years or above
  • Gender: All

Inclusion Criteria:

  1. Male and female subjects at least 12 years of age who have had allogenic hematopoietic cell transplant (HCT).
  2. Previously received at least 2 and not more than 5 lines of systemic therapy for cGVHD
  3. Receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to screening
  4. Have persistent cGVHD manifestations and systemic therapy is indicated
  5. Karnofsky Performance Score of ≥ 60 (if aged 16 years or older); Lansky Performance Score of ≥ 60 (if aged < 16 years)
  6. Weight ≥ 40kg

Exclusion Criteria:

  1. Subjects has not been on a stable dose / regimen of systemic cGVHD treatments for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus, MMF, methotrexate, rituximab, and extracorporeal photophoresis (ECP) are acceptable. Systemic investigational GVHD treatments are not permitted).
  2. Histological relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
  3. Current treatment with ibrutinib. Prior treatment with ibrutinib is allowed with a washout of at least 28 days prior to randomization.

This study investigates the efficacy and safety of an investigational medication for individuals with Chronic Graft Versus Host Disease (cGVHD) who have previously undergone at least two systemic treatments. The study includes two treatment arms where participants receive different doses of the investigational medication.

Participants will receive treatment in 28-day cycles. They will be randomly assigned to one of two arms: Arm A, where they will take the investigational medication once daily, or Arm B, where they will take it twice daily. The study will monitor the overall response rate, which is the proportion of participants experiencing a significant improvement in their cGVHD symptoms.

  • Who can participate: Participants must be at least 12 years old, have had an allogenic hematopoietic cell transplant, and received at least two prior lines of therapy for cGVHD. They should have a stable dose of glucocorticoid therapy and a performance score of 60 or higher. Participants must weigh at least 40 kg. Exclusion criteria include a histological relapse of underlying cancer and being on investigational GVHD treatments.
  • Study details: Participants will take the investigational medication either once or twice daily, depending on their assigned group. The study will evaluate their response to the treatment over 28-day cycles.
Updated on 12 Dec 2024. Study ID: NCT03640481