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

Chronic Graft Versus Host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05567406
• Other study ID #: SFY17661
• Secondary ID: U1111-1277-6715K
• Status: Recruiting
• Phase: Phase 2
• Start date: May 2, 2024
• Est. completion date: August 27, 2025

Study information

• Verified date: March 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: August 27, 2025
• Est. primary completion date: August 27, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bronchiolitis Obliterans Syndrome
• Chronic Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Belumosudil
Pharmaceutical form: Tablet; Route of administration: Oral

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute Site Number : 004	Boston	Massachusetts
United States	Massachusetts General Hospital Site Number : 002	Boston	Massachusetts
United States	Washington University School of Medicine Site Number : 125	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Kadmon, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of participants with clinically significant laboratory abnormalities		Up to approximately 12 months
Primary	Change from baseline in systolic and diastolic blood pressure		Baseline; up to approximately 12 months
Primary	Change from baseline in heart rate		Baseline; up to approximately 12 months
Primary	Change from baseline in corrected QT interval using Fridericia's formula (QTc[F])		Baseline; up to approximately 12 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in calcineurin inhibitor dose	The change in calcineurin inhibitor dose over time will be determined.	Baseline; up to approximately 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in symptom activity as based on cGVHD Activity Assessment Patient Self-Report	Patient-reported outcome	Baseline; up to approximately 12 months
Secondary	Plasma belumosudil concentrations		Day 1 of Cycles 2, 3, 5, and 7 (1 Cycle = 28 days)