A Study to Test an Oral Medicine, Belumosudil, in Combination With Corticosteroids in Participants at Least 12 Years of Age With Newly Diagnosed Chronic Graft Versus Host Disease.

PHASE3RECRUITING

This is a parallel, Phase 3, two-arm study for the treatment of newly diagnosed moderate or severe chronic GVHD. The study duration for a participant includes up to 4 weeks for screening; a treatment period until clinically meaningful cGVHD progression (defined as progression requiring addition of new systemic treatment for cGVHD), relapse/recurrence of the underlying disease, participant starts new systemic treatment for cGVHD or experiences an unacceptable toxicity, at the request of the participants or the investigators, or until the end of study is reached, whichever comes first; at least 30 days follow-up of adverse events (AEs) after the last dose until resolution or stabilization, if applicable; and long-term follow-up until death or study close-out, whichever comes first.

info
Simpliy with AI

Study details:

Up to 5 years.

info
Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Patients must be at least 12 years of age inclusive, at the time of signing the informed consent
  • Participants who have undergone allogenic HCT with newly diagnosed moderate to severe cGVHD according to NIH consensus diagnosis and staging criteria (2014)
  • Participants who require systemic treatment with corticosteroids for cGVHD
  • Participants who have not received any prior systemic treatment for cGVHD (including ECP)
  • If participants are receiving other immunosuppressive agents for the prophylaxis or treatment of acute GVHD, the dose should be under the threshold pre-defined in protocol
  • Body weight ≥ 40kg
  • Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Participants or their legally authorized representative must be capable of giving signed informed consent
  • Exclusion criteria

  • Histological relapse of the underlying disease after most recent allogeneic HCT
  • Post-transplant lymphoproliferative disease within 4 weeks prior to randomization
  • Female participants who are pregnant or breastfeeding
  • Unable to tolerate a prednisone equivalent dose of corticosteroids ≥ 1 mg/kg/day
  • Participant has had previous exposure to belumosudil.
  • Received any previous systemic treatment for cGVHD with the following exception: Corticosteroids for cGVHD received within 7 days prior to the planned administration of IMP only if in the interest of participant.
  • Received any investigational agents, or any investigational device or procedure, or prohibited therapy for this study within 28 days or 5 elimination half-lives prior to randomization, whichever is longer
  • Karnofsky (if aged ≥16 years)/Lansky (if aged <16 years) Performance Score of < 60
  • Platelets <50 x 10^9/L. Platelet transfusion is not allowed within 3 days before the screening hematological test
  • Absolute neutrophil count (ANC) <1.0 x 10^9/L. The use of granulocyte-colony stimulating factor (G-CSF) is not allowed to reach this level during screening
  • Estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73 m2 using the MDRD-4 variable formula (if aged ≥18 years) or using the Bedside Schwartz formula (if aged <18 years)
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN without liver cGVHD (or >5 × ULN if due to cGVHD with liver cGVHD)
  • Total bilirubin >1.5 × (ULN) (>3 × ULN if Gilbert syndrome)
  • Participant has forced expiratory volume in 1 second (FEV1) of predicted ≤39% or has lung score of 3 according to NIH consensus diagnostic and staging criteria (2014)
  • 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, poorly controlled psychiatric disease or coronary artery disease)
  • Known history of human immunodeficiency virus (HIV)
  • Active viral disease including hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • Active uncontrolled cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection worsening are present according to Investigator's judgement
  • Diagnosed or treated for another malignancy other than the underlying disease allogeneic HCT was indicated for, within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy
  • Unable to swallow tablets
  • 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
  • Any active, uncontrolled infections assessed to be clinically significant by the Investigator
  • info
    Simplify with AI

    Eligibility

    Age eligible for study : 12 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2024-01-23

    Primary completion: 2028-09-29

    Study completion finish: 2028-09-29

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE3

    trial

    Trial ID

    NCT06143891

    Intervention or treatment

    DRUG: Belumosudil

    DRUG: Placebo

    DRUG: Prednisone

    DRUG: Prednisolone

    Conditions

    • Chronic Graft Versus Host Disease

    Find a site

    Closest Location:

    Investigational Site Number : 0360005

    Research sites nearby

    Select from list below to view details:

    • Investigational Site Number : 0360005

      Westmead, New South Wales, Australia

    • Investigational Site Number : 0360003

      Herston, Queensland, Australia

    • Investigational Site Number : 0360001

      Melbourne, Victoria, Australia

    • Investigational Site Number : 0360004

      Murdoch, Western Australia, Australia

    Loading...

    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: Belumosudil
    • Participants will receive belumosudil 200 mg tablets Per os(PO) once daily (QD) per 28-day cycles starting on Day 1 until discontinuation criteria are met or until end of study
    • note: 200mg two times a day (BID) is used in some cases, when the subject is taking a proton pump inhibitor or a strong CYP3A4 inducer)
    DRUG: Belumosudil
    • Pharmaceutical form:Tablet-Route of administration:oral
    PLACEBO_COMPARATOR: Placebo
    • Participants will receive matching placebo tablets PO QD per 28-day cycles starting on Day 1 until discontinuation criteria are met or until end of study
    DRUG: Placebo
    • Pharmaceutical form:Table-Route of administration:oral

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Event-Free Survival (EFS)from the date of randomization to the date of any predefined event, whichever occurs firstUntil the end of the study (up to 5 years since first patient in).

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    modified Lee Symptom Scale (mLSS)Proportion of participants who achieve a clinically relevant reduction in mLSS of at least 6 points from baseline (Only in participants at least 18 years of age)Until the end of the study (up to 5 years since first patient in).
    overall response rate (ORR)Proportion of participants who achieve an overall response (PR or CR) as per 2014 NIH consensus response criteria by 48 weeks and maintained the response for a duration of at least 6 monthsUntil the end of the study (up to 5 years since first patient in).
    rate of corticosteroid withdrawalProportion of participants who successfully discontinue all systemic corticosteroids for cGVHD for at least 30 days before the occurrence of cGVHD progression, or start of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or unacceptable toxicityUntil the end of the study (up to 5 years since first patient in).
    Overall response rate (ORR)Proportion of participants who achieve an overall response (CR or PR) as per 2014 NIH consensus response criteria at any time before the start of new systemic treatment for cGVHDUntil the end of the study (up to 5 years since first patient in).
    ORR by 24 weeksProportion of participants who achieve an overall response (CR or PR) as per 2014 NIH consensus response criteria by 24 weeks (Cycle 7 Day 1) before the start of new systemic treatment for cGVHDUntil the end of the study (up to 5 years since first patient in).
    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 criteriaUntil the end of the study (up to 5 years since first patient in).
    Dose reduction in corticosteroidProportion of participants with a reduction in daily corticosteroid doseUntil the end of the study (up to 5 years since first patient in).
    Failure Free Survival (FFS)Failure Free Survival (FFS) is defined as the time from the date of randomization to the date of start of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or death, whichever occurs first.Until the end of the study (up to 5 years since first patient in).
    Change in patient reported outcome (PRO)Change from baseline in Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) (Only in participants at least 18 years of age) and the European Quality of Life Group Questionnaire with 5 Dimensions and 5 Levels (EQ5D5L)Until the end of the study (up to 5 years since first patient in).
    Number of participants with treatment-emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)Not SpecifiedUntil the end of the study (up to 5 years since first patient in).
    Overall survivalThe time from the date of randomization to the date of death due to any causeUntil the end of the study (up to 5 years since first patient in).

    Frequently Asked Questions

    Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

    No questions submitted. Be the first to ask a question!

    You may be eligible to participate in this trial based on your search.Apply for study
    Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

    References

    Clinical Trials Gov: A Study to Test an Oral Medicine, Belumosudil, in Combination With Corticosteroids in Participants at Least 12 Years of Age With Newly Diagnosed Chronic Graft Versus Host Disease.

    Other trails to consider

    Top searched conditions