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

Kadmon, a Sanofi Company

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Chronic Graft Versus Host Disease

Interventions

BelumosudilDRUG

Pharmaceutical form: Tablet; Route of administration: Oral

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Up to approximately 48 months

Number of participants with clinically significant laboratory abnormalities

Time frame: Up to approximately 12 months

Change from baseline in systolic and diastolic blood pressure

Time frame: Baseline; up to approximately 12 months

Change from baseline in heart rate

Time frame: Baseline; up to approximately 12 months

Change from baseline in corrected QT interval using Fridericia's formula (QTc[F])

Time frame: 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.

Time frame: Up to approximately 12 months

Secondary Outcomes

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

Time frame: Up to approximately 12 months

Change from baseline in the Lee Symptom Scale Score: Number of participants with a ≥ 7-point reduction

Data from ClinicalTrials.gov

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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.

Time frame: 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

Time frame: Baseline; up to approximately 12 months

Change from baseline in the Lee Symptom Scale Score: Duration of a ≥ 7 point reduction

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline; up to approximately 12 months

Change from baseline in calcineurin inhibitor dose

The change in calcineurin inhibitor dose over time will be determined.

Time frame: 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.

Time frame: 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.

Time frame: Up to approximately 12 months

Change from baseline in cGVHD global severity rating using the Clinician-Reported Global cGVHD Activity Assessment

Patient-reported outcome

Time frame: Baseline; up to approximately 12 months

Change from baseline in symptom activity as based on cGVHD Activity Assessment Patient Self-Report

Patient-reported outcome

Time frame: Baseline; up to approximately 12 months

Plasma belumosudil concentrations

Time frame: Day 1 of Cycles 2, 3, 5, and 7 (1 Cycle = 28 days)