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

Kadmon

Status and phase: Terminated; Phase 2

Conditions: Chronic Graft-versus-host-disease

Treatments: Drug: Belumosudil (KD025)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03640481

KD025-213

U1111-1279-2518 (Registry Identifier)

DRI17633

Details and patient eligibility

About

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

Full description

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 Subjects who have not achieved a response after 12 cycles of belumosudil should be withdrawn if in the Investigator's judgment there is no evidence of clinical benefit.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.

Enrollment: 159 patients

Sex: All

Ages: 12+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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159 participants in 4 patient groups

Arm A: belumosudil 200 mg, QD, adult arm

Experimental group

Description:

Eligible subjects randomized to arm A will take belumosudil 200 mg once daily

Treatment:

Drug: Belumosudil (KD025)

Arm B: belumosudil 200 mg, BID, adult arm

Experimental group

Description:

Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily

Treatment:

Drug: Belumosudil (KD025)

Adolescent arm A: belumosudil 200 mg QD

Experimental group

Description:

Eligible subjects randomized to arm A will take belumosudil 200 mg once daily

Treatment:

Drug: Belumosudil (KD025)

Adolescent arm B: belumosudil 200 mg BID

Experimental group

Description:

Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily

Treatment:

Drug: Belumosudil (KD025)