Safety and Efficacy of Oral Belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander Male and Female Participants Aged 12 Years and Above With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy

Study Overview
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Brief Summary
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The purpose of this study is to measure safety and efficacy of oral belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander male and female participants with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy aged 12 years and above. The duration of participants participation will be up to 4 weeks for screening, treatment until clinically significant progression of disease, and 4 weeks of safety follow-up, and then long-term follow-up every 12 weeks.1 Cycle = 28 days.

Detailed Description
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Up to 4 weeks for screening, treatment until clinically significant progression of disease, 4 weeks of safety follow-up and then long-term follow-up every 12 weeks.

Official Title
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A Phase 2, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander Participants With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy

Conditions
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Chronic Graft Versus Host Disease

Intervention / Treatment
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* Drug: Belumosudil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants are included in the study if any of the following criteria apply: Participant is Black or African American, or American Indian or Alaska Native, or Native Hawaiian or Other Pacific Islander by self-identification. Previously received at least 2 and not more than 5 lines of systemic therapy for cGVHD. Receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to screening. Have persistent cGVHD manifestations and systemic therapy is indicated. Karnofsky (if aged ≥ 16 years) / Lansky (if aged < 16 years) Performance Score of ≥ 60. At least 12 years of age; weight ≥ 40 kilograms (kg). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN). Total bilirubin ≤ 1.5 x ULN. Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants Capable of giving signed informed consent. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Participant has not been on a stable dose/regimen of systemic cGVHD treatment(s) for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus, MMF, methotrexate, rituximab, and ECP are acceptable. Systemic investigational GVHD treatments are not permitted). Histological relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening. Current treatment with ibrutinib or ruxolitinib. Prior treatment with ibrutinib or ruxolitinib is allowed with a washout of at least 28 days prior to enrollment. History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease, or coronary artery disease). Corrected QT interval using Fridericia's formula (QTc[F]) > 480 ms. Forced expiratory volume (in the first second; FEV1) ≤ 39% The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belumosudil<br>Participants will receive belumosudil orally, once daily (QD) or twice daily (BID) if they are taking strong CYP3A4 inducers or proton pump inhibitors. | Drug: Belumosudil<br>* Pharmaceutical form: Tablet; Route of administration: Oral<br>* Other names: Rezurock;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment emergent adverse events and serious adverse events | Safety will be assessed by monitoring adverse events, physical Examinations, clinical laboratory evaluations, vital sign measurements, and ECG parameters. | Up to approximately 48 months | 
| Number of participants with clinically significant laboratory abnormalities |  | Up to approximately 12 months | 
| Change from baseline in systolic and diastolic blood pressure |  | Baseline; up to approximately 12 months | 
| Change from baseline in heart rate |  | Baseline; up to approximately 12 months | 
| Change from baseline in corrected QT interval using Fridericia's formula (QTc[F]) |  | Baseline; up to approximately 12 months | 
| Overall Response Rate (ORR) | The ORR is defined as the proportion of participants meeting the overall response criteria assessment of Complete Response (CR) or Partial Response (PR) as defined by the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD at any post-baseline response assessment. | Up to approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | Assessments of DOR includes The time from first response to progression, death, or new systemic therapy for cGVHD Time from initial response to start of additional systemic cGVHD therapy or death | Up to approximately 12 months | 
| Change from baseline in the Lee Symptom Scale Score: Number of participants with a ≥ 7-point reduction | Changes in symptom burden/bother will be assessed using the Lee Symptom Scale, a symptom scale designed for individuals with chronic Graft Versus Host Disease (cGVHD). The questionnaire asks participants to indicate the degree of bother that they experienced due to symptoms in seven domains potentially affected by cGVHD (skin, eyes, mouth, breathing, eating and digestion, energy, and emotional distress). The response will be determined based on clinician's assessment. | Baseline; up to approximately 12 months | 
| Change from baseline in the Lee Symptom Scale Score: Number of participants with a ≥ 7-point reduction on 2 consecutive assessments | Changes in symptom burden/bother will be assessed using the Lee Symptom Scale, a symptom scale designed for individuals with chronic Graft Versus Host Disease (cGVHD). The questionnaire asks participants to indicate the degree of bother that they experienced due to symptoms in seven domains potentially affected by cGVHD (skin, eyes, mouth, breathing, eating and digestion, energy, and emotional distress). The response will be determined based on clinician's assessment. | Baseline; up to approximately 12 months | 
| Change from baseline in the Lee Symptom Scale Score: Duration of a ≥ 7 point reduction | Changes in symptom burden/bother will be assessed using the Lee Symptom Scale, a symptom scale designed for individuals with chronic Graft Versus Host Disease (cGVHD). The questionnaire asks participants to indicate the degree of bother that they experienced due to symptoms in seven domains potentially affected by cGVHD (skin, eyes, mouth, breathing, eating and digestion, energy, and emotional distress). The response will be determined based on clinician's assessment. | Baseline; up to approximately 12 months | 
| Response rate by organ system | The response rate for the nine individual organs (skin, eyes, mouth, esophagus, upper GI, lower GI, liver, lungs, and joints and fascia) will be assessed by the clinician. | Up to approximately 12 months | 
| Time to Response (TTR) | TTR defined as the time from the first dose of belumosudil to the first documented cGVHD response. | Up to approximately 12 months | 
| Time to Next Treatment (TTNT) | TTNT defined as the time from the first dose of belumosudil to the start of additional systemic cGVHD therapy. | Up to approximately 12 months | 
| Number of participants who have a best response of PR and CR | CR is defined as resolution of all manifestations of cGVHD in each organ or site. PR is defined as Improvement in at least 1 organ or site without progression in any other organ or site. | Up to approximately 12 months | 
| Change from baseline in corticosteroid dose | The prednisone equivalent dose of corticosteroids (mg/kg/day) during the study will be analyzed. The change in systemic corticosteroid dose over time will be determined. | Baseline; up to approximately 12 months | 
| Change from baseline in calcineurin inhibitor dose | The change in calcineurin inhibitor dose over time will be determined. | Baseline; up to approximately 12 months | 
| Failure-free survival (FFS) | FFS defined as the absence of new cGVHD systemic therapy, non-relapse mortality and recurrent malignancy. Median FFS (from first dose of belumosudil) will be analyzed. | Up to approximately 12 months | 
| Overall survival (OS) | OS defined as time from first dose of belumosudil to the date of death due to any cause. | Up to approximately 12 months | 
| Change from baseline in cGVHD global severity rating using the Clinician-Reported Global cGVHD Activity Assessment | Patient-reported outcome | Baseline; up to approximately 12 months | 
| Change from baseline in symptom activity as based on cGVHD Activity Assessment Patient Self-Report | Patient-reported outcome | Baseline; up to approximately 12 months | 
| Plasma belumosudil concentrations |  | Day 1 of Cycles 2, 3, 5, and 7 (1 Cycle = 28 days) |