BELUMOSUDIL MESILATE for Chronic graft versus host disease

Inclusion criteria

• {"criterion_text":"- Participant must be 1 to <18 years of age, at the time the consent/assent is signed. For Phase 1: participant must be 1 to <12 years of age, at the time the consent/assent is signed. For Phase 2: participant must be 1 to <18 years of age, at the time the consent/assent is signed."}
• {"criterion_text":"- Life expectancy of >6 months"}
• {"criterion_text":"- Participants can take the IMP orally or via a nasogastric tube"}
• {"criterion_text":"- Participant has undergone an allogeneic HCT"}
• {"criterion_text":"- Has active moderate to severe cGVHD, defined using the NIH Consensus diagnosis and staging criteria for which systemic therapy is required"}
• {"criterion_text":"- cGVHD is refractory to or has recurred after at least 2 prior lines of systemic treatment"}
• {"criterion_text":"- Has received at least two lines of prior systemic therapy for cGVHD, but no more than 5 lines."}
• {"criterion_text":"- If participant receives corticosteroid therapy for cGVHD, the dose must be stable for at least 2 weeks prior to the first dose of the IMP"}
• {"criterion_text":"- Has a Lansky-Play (if aged ≤16) or Karnofsky (if aged >16) performance scale of ≥60"}
• {"criterion_text":"- Body weight of 8 kg and above"}
• {"criterion_text":"- Contraceptive use by sexually active male and female should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies"}

Exclusion criteria

• {"criterion_text":"- Progressive underlying disease or post-transplant lymphoproliferative disease within 4 weeks prior to the first dose of the IMP."}
• {"criterion_text":"- Treatment with any non-GVHD investigational agent, or any investigational device or procedure, within 28 days (or 5 half-lives, whichever is longer) of enrollment, prior to the first dose of the IMP"}
• {"criterion_text":"- For Phase 1 only: Administration with strong CYP3A4 inducers is not allowed within 14 days or 5 half-lives (whichever is longer) of the first dose of IMP until the study intervention discontinuation."}
• {"criterion_text":"- For Phase 1 only: PPIs are not allowed within 1 day or 5 half-lives (whichever is longer) of the first dose of IMP and Day 15 of Cycle 1. They can be restarted on Cycle 1 Day 16."}
• {"criterion_text":"- Absolute neutrophil count <1.0 × 109/L. The use of granulocyte-colony stimulating factor (G-CSF) is not allowed to reach this level during screening"}
• {"criterion_text":"- Platelet count <25× 109/L. Platelet transfusions are not allowed within 72 hours before hematology screening test. Participants with platelet transfusion refractoriness will be excluded. (Participants who have suboptimal responses to at least 2 transfusions will be considered as platelet transfusion refractory)"}
• {"criterion_text":"- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3× upper limit of normal (ULN) (> 5x ULN if abnormalities are due to cGVHD)"}
• {"criterion_text":"- Total bilirubin >1.5 × ULN (>3 x ULN if Gilbert’s syndrome)"}
• {"criterion_text":"- Glomerular filtration rate (GFR) <30 mL/min/1.73 m2 using the revised Bedside Schwartz calculator"}
• {"criterion_text":"- Participants with an active viral disease including hepatitis B virus (HBV) and hepatitis C virus (HCV)"}
• {"criterion_text":"- Active uncontrolled Cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection"}
• {"criterion_text":"- Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years prior to the first dose of the IMP"}
• {"criterion_text":"- Known history of human immunodeficiency virus (HIV)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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, active, uncontrolled infections, or poorly controlled psychiatric disease)"}
• {"criterion_text":"- Has a forced expiratory volume (in the first second; FEV1) ≤ 39% or has lung score of 3"}
• {"criterion_text":"- Female participants who are pregnant or breastfeeding"}
• {"criterion_text":"- Current treatment with systemic agents for cGVHD (apart from corticosteroids and calcineurin inhibitors), such as ibrutinib, ruxolitinib, sirolimus, mycophenolate (MMF), methotrexate, rituximab, imatinib, extracorporeal photopheresis (ECP) and any investigational cGVHD treatment. Prior treatment with these agents and/or therapy is allowed with a washout of at least 28 days or 5 half-lives, whichever is shorter, prior to the first dose of the IMP"}
• {"criterion_text":"- The use of herbal and recreational drugs within 7 days before the start of study intervention"}
• {"criterion_text":"- Participant has had previous exposure to belumosudil"}
• {"criterion_text":"- Administration of live or live-attenuated vaccines is prohibited within 28 days or 5 elimination half-lives of the respective vaccine, whichever is longer, prior to IMP administration and until study intervention discontinuation"}

Primary endpoints

• {"endpoint_text":"- Phase 1: AUC","definition_or_measurement_approach":"Area under the concentration-time curve (AUC) as a pharmacokinetic parameter (Phase 1 PK measurement)."}
• {"endpoint_text":"- Phase 2: Proportion of participants who achieve an overall response (partial response [PR] or complete response [CR]) by Week 25 or Cycle 7 Day 1 whichever is first","definition_or_measurement_approach":"Proportion (percentage) of participants achieving overall response defined as PR or CR assessed by the study's response criteria by Week 25 or Cycle 7 Day 1, whichever occurs first."}

Secondary endpoints

• {"endpoint_text":"- Phase 1: Number of participants with treatment- emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)","definition_or_measurement_approach":"Counts and incidence of TEAEs, serious TEAEs and AESIs collected throughout treatment (safety monitoring)."}
• {"endpoint_text":"- Phase 1: Cmax","definition_or_measurement_approach":"Maximum observed plasma concentration (Cmax) measured in PK sampling."}
• {"endpoint_text":"- Phase 1: AUC0-6h","definition_or_measurement_approach":"AUC from time 0 to 6 hours (AUC0-6h) as a PK parameter measured in Phase 1."}
• {"endpoint_text":"- Phase 1: ORR","definition_or_measurement_approach":"Overall response rate (ORR) measured per study response criteria in Phase 1."}
• {"endpoint_text":"- Phase 1: DOR","definition_or_measurement_approach":"Duration of response (DOR) as measured from response until relapse or progression."}
• {"endpoint_text":"- Phase 1: response by organ","definition_or_measurement_approach":"Organ-specific response assessments as defined in the protocol (response per organ)."}
• {"endpoint_text":"- Phase 1: failure-free survival (FFS)","definition_or_measurement_approach":"Time-to-event endpoint measuring time until failure (per protocol definition)."}
• {"endpoint_text":"- Phase 1: overall survival (OS)","definition_or_measurement_approach":"Time from enrollment to death from any cause."}
• {"endpoint_text":"- Phase 1: time to response (TTR)","definition_or_measurement_approach":"Time from first dose to first documented response."}
• {"endpoint_text":"- Phase 2: Number of participants with treatment- emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)","definition_or_measurement_approach":"Counts and incidence of TEAEs, serious TEAEs and AESIs collected throughout treatment (safety monitoring) in Phase 2."}
• {"endpoint_text":"- Phase 2: Ctrough of belumosudil","definition_or_measurement_approach":"Trough plasma concentration (Ctrough) of belumosudil measured at designated timepoints."}
• {"endpoint_text":"- Phase 2: DOR","definition_or_measurement_approach":"Duration of response measured in Phase 2 from first response until relapse/progression."}
• {"endpoint_text":"- Phase 2: response by organ","definition_or_measurement_approach":"Organ-specific response assessments as defined in protocol for Phase 2."}
• {"endpoint_text":"- Phase 2: FFS","definition_or_measurement_approach":"Failure-free survival as defined in the protocol for Phase 2."}
• {"endpoint_text":"- Phase 2: OS","definition_or_measurement_approach":"Overall survival measured in Phase 2."}
• {"endpoint_text":"- Phase 2: time to response (TTR)","definition_or_measurement_approach":"Time from first dose to first documented response in Phase 2."}

Methods

• Referral letters to healthcare professionals (referal-letter-to-hp) in multiple languages (EN/FR/DE/NL/IT/ES) to inform HCPs about the study (document titles: K2-recruitment-material-referal-letter-to-hp-*)
• Infographic patient brochure / patient-facing brochures (K2-recruitment-material-infographic-patient-brochure-*) targeted to patients and caregivers
• Understanding-study video materials with OST and voiceover scripts (K2-recruitment-material-understanding-study-video-ost-script-*, -vo-script-*) for patient/caregiver education
• Study passports and age-specific study passports for children/adolescents (K2-recruitment-material-study-passport-7-12, -13-17) for families and participants
• K1 recruitment arrangements documents (K1-recruitment-arrangements-en and localized versions) describing recruitment approach
• Patient diary materials (d4-patient-facing-material-patient-diary-*) provided to participants as part of study procedures

France

Earliest CTIS Part Ii Submission Date

17-09-2025

Latest Decision Or Authorization Date

30-09-2025

Processing Time Days

13

Number Of Sites

2

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

01-10-2025

Processing Time Days

19

Number Of Sites

2

Number Of Participants

3

Belgium

Earliest CTIS Part Ii Submission Date

01-09-2025

Latest Decision Or Authorization Date

14-11-2025

Processing Time Days

74

Number Of Sites

2

Number Of Participants

3

Italy

Earliest CTIS Part Ii Submission Date

18-08-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

91

Number Of Sites

3

Number Of Participants

5

Netherlands

Earliest CTIS Part Ii Submission Date

02-09-2025

Latest Decision Or Authorization Date

04-11-2025

Processing Time Days

63

Number Of Sites

1

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

15-09-2025

Latest Decision Or Authorization Date

31-10-2025

Processing Time Days

46

Number Of Sites

4

Number Of Participants

5

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Endpoint Clinical Inc.

Responsibilities

sponsorDuties code 3

Name

Labcorp Central Laboratory Services LP

Responsibilities

sponsorDuties code 4 (central laboratory services)

Third parties

• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"sponsorDuties code 3","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"sponsorDuties code 15 (Centralized 24-Hour Emergency System)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"sponsorDuties code 14","organisation_type":"Pharmaceutical company"}