Chronic Graft Versus Host Disease
Conditions
Brief summary
This is a single group, Phase 4, single-arm post-marketing study for treatment. The purpose of this study is to verify the pharmacokinetics, efficacy, and safety of belumosudil mesylate tablets in Chinese adolescent participants (aged from 12 to less than 18) with cGVHD who have had an inadequate response to glucocorticoids or other systemic therapies. Participants will receive treatment with belumosudil tablets 200 mg once daily in 28-day cycles during the study.
Interventions
DRUGBelumosudil
Pharmaceutical form: Tablet Route of administration: Oral
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be 12 to less than 18 years of age at the time of signing the informed consent. * Participant has undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). * Has active moderate to severe cGVHD. * Has received at least one line of prior systemic therapy for cGVHD. * Participant must receive a corticosteroid therapy for cGVHD with a stable dose for at least 2 weeks prior to the first dose of the IMP. * Has a Lansky-Play performance score of ≥60. * Participants should have an expected survival of longer than 6 months. * Body weight of 30 kg and above. * Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * The participant or their legally authorized representative (LAR) must be capable of giving signed informed consent.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * Recurrence of hematologic neoplasms (according to the corresponding criteria for recurrence of primary hematologic neoplasms) or post-transplant lymphoproliferative disease at screening. * Received investigational systemic therapy for cGVHD within 28 days prior to enrollment, unless the prior treatment had been washed out for at least 28 days or 5 half-lives prior to enrollment, whichever is shorter. * Absolute neutrophil count (ANC) \<1.0 × 10\^9/L. * Platelet count \<50 × 10\^9/L. * Alanine aminotransferase (ALT) \>3× the upper limit of normal (ULN), aspartate aminotransferase (AST) \>3 × ULN. * Total bilirubin (TBIL) \>1.5 × ULN (\>3 ULN if Gilbert's syndrome). * Estimated Glomerular Filtration Rate (eGFR) \<30 mL/min/1.73 m\^2 using the revised Bedside Schwartz formula . Revised Schwartz equation: CrCl (mL/min/1.73 m\^2) = 0.413 × (height \[in cm\])/Creatinine (in mg/dL) at screening visit. * Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma concentrations of belumosudil at specified time points | At Day 1 and Day 29(±3) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DoR) | Up to 18 month | Duration of response (DoR): time from the date of the first response to the date of cGVHD progression as defined by 2014 NIH consensus response criteria, start of new systemic treatment for cGVHD, or death, whichever occurs first. DOR is determined only for participants who achieved overall response (PR or CR) as per 2014 NIH consensus response criteria. |
| System organ response rate | Up to 18 month | System organ response rate: proportion of participants who achieve an overall response (CR or PR) for each of the nine individual organs (Skin, Eyes, Mouth, Esophagus, Upper GI, Lower GI, Liver, Lungs, and Joints and fascia) as per 2014 NIH consensus response criteria at any time before the start of new systemic treatment for cGVHD |
| Number and proportion of participants with dose reduction in corticosteroid during the treatment period | Up to 18 month | — |
| Failure-free survival (FFS) | Up to 18 month | Failure-free survival (FFS): time from the date of the first administration of IMP to 1) the date of initiation of new systemic treatment for cGVHD, or 2) date of death, or 3) date of recurrent underlying disease, whichever occurs first |
| Overall survival (OS) | Up to 18 month | Overall survival (OS): time from the date of the first administration of IMP to the date of death due to any cause |
| Overall response rate (ORR) | Up to 18 month | Overall response rate (ORR, including complete response \[CR\] and partial response \[PR\]), which will be assessed by the investigator according to the NIH Consensus Criteria (2014) at any time before the start of new systemic treatment for cGVHD. |
| Change in symptom activity assessed based on patient-reported cGVHD activity | Up to 18 month | — |
| Modified Lee cGVHD Symptom Scale change | Up to 18 month | The scale contains 30 items grouped in 7 subscales (skin, eye, mouth, lung, nutrition, energy, and psychological). Patients report how bothered they feel about each symptom using a five-point Likert scale from not at all (0) to extremely (4). A higher score indicating worse symptoms, reporting score will be normalizing to a 0 to 100 scale. |
| Number and proportion of participants with calcineurin inhibitor (CNI) dose reduction or discontinuation during the treatment period | Up to 18 month | — |
| Number of participants with treatment-emergent adverse events (TEAEs), serious TEAEs, and adverse events of special interest (AESIs) | Up to 18 month | — |
| Change in cGVHD severity based on physician-reported overall cGVHD activity | Up to 18 month | — |
Countries
China
Outcome results
None listed