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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

Phase 4
Recruiting
Conditions
Chronic Graft Versus Host Disease
Interventions
Registration Number
NCT06616415
Lead Sponsor
Sanofi
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
6
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BelumosudilBelumosudilParticipants will receive belumosudil 200 mg tablets orally QD in 28-day cycles until clinically significant progression of cGVHD
Primary Outcome Measures
NameTimeMethod
Plasma concentrations of belumosudil at specified time pointsAt Day 1 and Day 29(±3)
Secondary Outcome Measures
NameTimeMethod
Number and proportion of participants with calcineurin inhibitor (CNI) dose reduction or discontinuation during the treatment periodUp 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 activityUp to 18 month
Change in symptom activity assessed based on patient-reported cGVHD activityUp to 18 month
System organ response rateUp 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

Modified Lee cGVHD Symptom Scale changeUp 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.

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.

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.

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

Trial Locations

Locations (2)

Investigational Site Number: 1560001

🇨🇳

Beijing, China

Investigational Site Number: 1560002

🇨🇳

Shanghai, China

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