Chronic graft-versus-host-disease MedDRA version: 27.0 Level: PT Classification code 10066261 Term: Chronic graft versus host disease System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Product Name: Sar445761
Product Code: Sar445761
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Belumosudil mesIlate
Current Sponsor code: Sar445761
Concentration unit: mg milligram(s)
Co
Sponsors
Kadmon Corporation, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants 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 Karnofsky Performance Score of = 60 (if aged 16 years or older); Lansky 5. Performance Score of = 60 (if aged =65 years) no F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1. Participant 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •The objective of this study is to evaluate the efficacy of belumosudil, at dose levels of 200 mg QD and 200 mg BID, in participants with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy;Secondary Objective: •The secondary objectives of the study are to evaluate: •Duration of response (DOR) •Changes in the Lee Symptom Scale Score •Response by organ system •Time to response (TTR) •Time to next treatment (TTNT) •Percentage of participants who have a best response of PR and percentage of participants who have a best response of CR •Change in corticosteroid dose •Change in calcineurin inhibitor dose •Failure-free-survival (FFS) •Overall survival (OS) •Change in cGVHD global severity rating using the Clinician-Reported Global cGVHD Activity Assessment •Change in symptom activity using the cGVHD Activity Assessment Patient Self-Report •PK of belumosudil in participants with cGVHD •Safety ;Primary end point(s): Overall Response Rate (ORR);Timepoint(s) of evaluation of this end point: up to approximately 40 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/ Duration of Response (DOR) 2/ Change in Lee Symptom Scale Score 3/ Response rate by organ system 4/ Percentage of participants who have a best response of PR or CR 5/ Change in corticosteroid dose 6/ Change in calcineurin inhibitor dose 7/ Failure-free survival (FFS) 8/ Overall Survival (OS) 9/ Change in cGVHD severity as based on the Physician-reported global cGVHD Activity Assessment 10/ Change in symptom activity as based on cGVHD Activity Assessment Patient Self-Report 11/ Determine the Peak Plasma Concentration (Cmax) of belumosudil 12/ Determine the observed time to reach peak plasma concentration (Tmax) of belumosudil 13/ Determine the half-life (T1/2) of belumosudil 14/ Determine the area under the plasma concentration versus time curve (AUC) of belumosudil 15/ Time to Response 16/ Time to next treatment 17/ Number pf participants with adverse event and serious adverse events;Timepoint(s) of evaluation of this end point: 1/ to 6/ and 9/ and 10/ and 15/ and 16/: up to approximately 40 months 7/ and 8/: up to approximately 7 years 11/ to 14/: Pre-dose and post-dose sampling within 12 hours 17/: Up to 28 days after the last dose of study treatment i.e., up to approximately 7 years | — |
Countries
United States
Contacts
Public Contact-
Sanofi-Aventis Recherche & Developpement
Outcome results
None listed