Clinical trial NCT05567406: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Graft Versus Host Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-10-05
Enrollment: 36
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with treatment emergent adverse events and serious adverse events
timeFrame: Up to approximately 48 months
measure: Number of participants with clinically significant laboratory abnormalities
timeFrame: Up to approximately 12 months
measure: Change from baseline in systolic and diastolic blood pressure
timeFrame: Baseline; up to approximately 12 months
measure: Change from baseline in heart rate
timeFrame: Baseline; up to approximately 12 months
measure: Change from baseline in corrected QT interval using Fridericia's formula (QTc[F])
timeFrame: Baseline; up to approximately 12 months
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 12 months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to approximately 12 months
measure: Change from baseline in the Lee Symptom Scale Score: Number of participants with a ≥ 7-point reduction
timeFrame: Baseline; up to approximately 12 months
measure: Change from baseline in the Lee Symptom Scale Score: Number of participants with a ≥ 7-point reduction on 2 consecutive assessments
timeFrame: Baseline; up to approximately 12 months
measure: Change from baseline in the Lee Symptom Scale Score: Duration of a ≥ 7 point reduction
timeFrame: Baseline; up to approximately 12 months
measure: Response rate by organ system
timeFrame: Up to approximately 12 months
measure: Time to Response (TTR)
timeFrame: Up to approximately 12 months
measure: Time to Next Treatment (TTNT)
timeFrame: Up to approximately 12 months
measure: Number of participants who have a best response of PR and CR
timeFrame: Up to approximately 12 months
measure: Change from baseline in corticosteroid dose
timeFrame: Baseline; up to approximately 12 months
measure: Change from baseline in calcineurin inhibitor dose
timeFrame: Baseline; up to approximately 12 months
measure: Failure-free survival (FFS)
timeFrame: Up to approximately 12 months
measure: Overall survival (OS)
timeFrame: Up to approximately 12 months
measure: Change from baseline in cGVHD global severity rating using the Clinician-Reported Global cGVHD Activity Assessment
timeFrame: Baseline; up to approximately 12 months
measure: Change from baseline in symptom activity as based on cGVHD Activity Assessment Patient Self-Report
timeFrame: Baseline; up to approximately 12 months
measure: Plasma belumosudil concentrations
timeFrame: Day 1 of Cycles 2, 3, 5, and 7 (1 Cycle = 28 days)
Other outcomes:
Locations:
city: Miami
country: United States
facility: Nicklaus Children's Hospital - Miami - Southwest 62nd Avenue- Site Number : 129
state: Florida
city: Baltimore
country: United States
facility: University of Maryland School of Medicine - Baltimore- Site Number : 128
state: Maryland
city: Valhalla
country: United States
facility: Westchester Medical Center- Site Number : 130
state: New York
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: