A Clinical Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Belumosudil in Chinese Adolescents With cGVHD Who Have Had an Inadequate Response to Glucocorticoids or Other Systemic Therapies

Sanofi6 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Graft Versus Host Disease

Interventions

Belumosudil

Eligibility

Sex: ALLMin age: 12 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Plasma concentrations of belumosudil at specified time points

Time frame: At Day 1 and Day 29(±3)

Secondary Outcomes

Overall response rate (ORR)

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.

Time frame: Up to 18 month

Duration of response (DoR)

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.

Time frame: Up to 18 month

System organ response rate

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

Time frame: Up to 18 month

Number and proportion of participants with dose reduction in corticosteroid during the treatment period

Time frame: Up to 18 month

Failure-free survival (FFS)

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

Time frame: Up to 18 month

Overall survival (OS)

Overall survival (OS): time from the date of the first administration of IMP to the date of death due to any cause

Time frame: Up to 18 month

Change in cGVHD severity based on physician-reported overall cGVHD activity

Time frame: Up to 18 month

Change in symptom activity assessed based on patient-reported cGVHD activity

Time frame: Up to 18 month

Modified Lee cGVHD Symptom Scale change

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.

Time frame: Up to 18 month

Number and proportion of participants with calcineurin inhibitor (CNI) dose reduction or discontinuation during the treatment period

Time frame: Up to 18 month

Number of participants with treatment-emergent adverse events (TEAEs), serious TEAEs, and adverse events of special interest (AESIs)

Time frame: Up to 18 month

A Clinical Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Belumosudil in Chinese Adolescents With cGVHD Who Have Had an Inadequate Response to Glucocorticoids or Other Systemic Therapies

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes