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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06143891




Registration number
NCT06143891
Ethics application status
Date submitted
16/11/2023
Date registered
22/11/2023
Date last updated
15/11/2024

Titles & IDs
Public title
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.
Scientific title
A Randomized, Double-blind, Multicenter, Phase 3 Study to Evaluate Efficacy and Safety of Belumosudil in Combination With Corticosteroids Versus Placebo in Combination With Corticosteroids in Participants at Least 12 Years of Age With Newly Diagnosed Chronic Graft Versus Host Disease (cGVHD)
Secondary ID [1] 0 0
2023-505394-32
Secondary ID [2] 0 0
EFC17757
Universal Trial Number (UTN)
Trial acronym
ROCKnrol-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Graft Versus Host Disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Belumosudil
Treatment: Drugs - Placebo
Treatment: Drugs - Prednisone
Treatment: Drugs - Prednisolone

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)

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


Treatment: Drugs: Belumosudil
Pharmaceutical form:Tablet-Route of administration:oral

Treatment: Drugs: Placebo
Pharmaceutical form:Table-Route of administration:oral

Treatment: Drugs: Prednisone
Pharmaceutical form:Tablet-Route of administration:oral

Treatment: Drugs: Prednisolone
Pharmaceutical form:Tablet-Route of administration:oral
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival (EFS)
Timepoint [1] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [1] 0 0
Modified Lee Symptom Scale (mLSS)
Timepoint [1] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [2] 0 0
Durable overall response rate
Timepoint [2] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [3] 0 0
Rate of corticosteroid withdrawal
Timepoint [3] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [4] 0 0
Overall response rate (ORR)
Timepoint [4] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [5] 0 0
ORR by 24 weeks
Timepoint [5] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [6] 0 0
Duration of response (DOR)
Timepoint [6] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [7] 0 0
Dose reduction in corticosteroid
Timepoint [7] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [8] 0 0
Failure Free Survival (FFS)
Timepoint [8] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [9] 0 0
Change in patient reported outcome (PRO)
Timepoint [9] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [10] 0 0
Number of participants with treatment-emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)
Timepoint [10] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [11] 0 0
Overall survival
Timepoint [11] 0 0
Until the end of the study (up to 5 years since first patient in).
Secondary outcome [12] 0 0
Time to response (TTR)
Timepoint [12] 0 0
Until the end of study (up to 5 years since first patient in)
Secondary outcome [13] 0 0
Response by organ
Timepoint [13] 0 0
Until the end of study (up to 5 years since first patient in)

Eligibility
Key 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
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:

Medical conditions

* 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 Prior/concomitant therapy
* 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.

Prior/concurrent clinical study experience

* 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 Diagnostic assessments
* Karnofsky (if aged =16 years)/Lansky (if aged <16 years) Performance Score of < 60
* Platelets <25 x 109/L. Platelet transfusion is not allowed within 3 days before the screening hematological test
* Absolute neutrophil count (ANC) <0.5 x 109/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 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/09/2028
Actual
Sample size
Target
260
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Investigational Site Number : 0360005 - Westmead
Recruitment hospital [2] 0 0
Investigational Site Number : 0360003 - Herston
Recruitment hospital [3] 0 0
Investigational Site Number : 0360001 - Melbourne
Recruitment hospital [4] 0 0
Investigational Site Number : 0360004 - Murdoch
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
6961 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
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Michigan
Country [9] 0 0
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North Carolina
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Ohio
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Oregon
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Tennessee
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Texas
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Virginia
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Washington
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Wisconsin
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Argentina
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Buenos Aires
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Argentina
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Ciudad De Buenos Aires
Country [20] 0 0
Austria
State/province [20] 0 0
Linz
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussels
Country [22] 0 0
Belgium
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Vlaams-Brabant
Country [23] 0 0
Belgium
State/province [23] 0 0
Gent
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Belgium
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Liège
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Belgium
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Roeselare
Country [26] 0 0
Brazil
State/province [26] 0 0
Paraná
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Brazil
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São Paulo
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Brazil
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Rio De Janeiro
Country [29] 0 0
Canada
State/province [29] 0 0
Alberta
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Quebec
Country [32] 0 0
Canada
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Saskatchewan
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China
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Changchun
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China
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Changsha
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Fuzhou
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Guangzhou
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Hangzhou
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China
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Hefei
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Jinan
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Tianjin
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Wuhan
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Zhengzhou
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Czechia
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Brno
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Czechia
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Hradec Kralove
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Czechia
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Ostrava
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Czechia
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Praha
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Capital
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Denmark
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Funen
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Jutland
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Pessac
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Pierre Benite
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France
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Rennes
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France
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Vandoeuvre-les-nancy
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Germany
State/province [58] 0 0
Berlin
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Germany
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Dresden
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Germany
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Hamburg
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Germany
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Kiel
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Germany
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Köln
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Germany
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Münster
Country [64] 0 0
Germany
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Tübingen
Country [65] 0 0
Greece
State/province [65] 0 0
Athens
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Greece
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Thessaloniki
Country [67] 0 0
Hong Kong
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HongKong
Country [68] 0 0
Israel
State/province [68] 0 0
Haifa
Country [69] 0 0
Israel
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Jerusalem
Country [70] 0 0
Israel
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Petach Tikva
Country [71] 0 0
Israel
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Ramat Gan
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Israel
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Tel Aviv
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Israel
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Tel HaShomer
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Italy
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Lombardia
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Italy
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Bergamo
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Italy
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Bologna
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Italy
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Genova
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Italy
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Milano
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Italy
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Perugia
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Italy
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Reggio Calabria
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Italy
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Roma
Country [82] 0 0
Italy
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Torino
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Italy
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Udine
Country [84] 0 0
Netherlands
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Amsterdam
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Netherlands
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Groningen
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Netherlands
State/province [86] 0 0
Rotterdam
Country [87] 0 0
Portugal
State/province [87] 0 0
Lisboa
Country [88] 0 0
Spain
State/province [88] 0 0
Andalucia
Country [89] 0 0
Spain
State/province [89] 0 0
Barcelona [Barcelona]
Country [90] 0 0
Spain
State/province [90] 0 0
Castilla Y Leon
Country [91] 0 0
Spain
State/province [91] 0 0
Cataluña
Country [92] 0 0
Spain
State/province [92] 0 0
Comunidad Valenciana
Country [93] 0 0
Spain
State/province [93] 0 0
Madrid, Comunidad De
Country [94] 0 0
Spain
State/province [94] 0 0
Madrid
Country [95] 0 0
Sweden
State/province [95] 0 0
Göteborg
Country [96] 0 0
Sweden
State/province [96] 0 0
Lund
Country [97] 0 0
Sweden
State/province [97] 0 0
Stockholm
Country [98] 0 0
Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Izmir
Country [102] 0 0
United Kingdom
State/province [102] 0 0
Vale Of Glamorgan, The
Country [103] 0 0
United Kingdom
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Leeds
Country [104] 0 0
United Kingdom
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Manchester
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06143891
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06143891