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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06143891




Registration number
NCT06143891
Ethics application status
Date submitted
16/11/2023
Date registered
22/11/2023
Date last updated
30/05/2024

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
overall response rate (ORR)
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).

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 <50 x 109/L. Platelet transfusion is not allowed within 3 days before the
screening hematological test

- Absolute neutrophil count (ANC) <1.0 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 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

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
240
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
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
United States of America
State/province [8] 0 0
Wisconsin
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Belgium
State/province [10] 0 0
Gent
Country [11] 0 0
Belgium
State/province [11] 0 0
Leuven
Country [12] 0 0
Belgium
State/province [12] 0 0
Roeselare
Country [13] 0 0
Belgium
State/province [13] 0 0
Sint-Lambrechts-Woluwe
Country [14] 0 0
Brazil
State/province [14] 0 0
São Paulo
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
Czechia
State/province [16] 0 0
Hradec Kralove
Country [17] 0 0
Czechia
State/province [17] 0 0
Praha 2
Country [18] 0 0
Denmark
State/province [18] 0 0
Aarhus N
Country [19] 0 0
Denmark
State/province [19] 0 0
Copenhagen
Country [20] 0 0
Denmark
State/province [20] 0 0
Odense C
Country [21] 0 0
Germany
State/province [21] 0 0
Dresden
Country [22] 0 0
Germany
State/province [22] 0 0
Hamburg
Country [23] 0 0
Germany
State/province [23] 0 0
Münster
Country [24] 0 0
Israel
State/province [24] 0 0
Haifa
Country [25] 0 0
Israel
State/province [25] 0 0
Jerusalem
Country [26] 0 0
Israel
State/province [26] 0 0
Petach Tikva
Country [27] 0 0
Israel
State/province [27] 0 0
Ramat Gan
Country [28] 0 0
Israel
State/province [28] 0 0
Tel Aviv
Country [29] 0 0
Israel
State/province [29] 0 0
Tel HaShomer
Country [30] 0 0
Italy
State/province [30] 0 0
Lombardia
Country [31] 0 0
Italy
State/province [31] 0 0
Bergamo
Country [32] 0 0
Italy
State/province [32] 0 0
Bologna
Country [33] 0 0
Italy
State/province [33] 0 0
Genova
Country [34] 0 0
Italy
State/province [34] 0 0
Milano
Country [35] 0 0
Italy
State/province [35] 0 0
Reggio Calabria
Country [36] 0 0
Italy
State/province [36] 0 0
Roma
Country [37] 0 0
Italy
State/province [37] 0 0
Torino
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona [Barcelona]
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid, Comunidad De
Country [40] 0 0
Spain
State/province [40] 0 0
Málaga
Country [41] 0 0
Spain
State/province [41] 0 0
Salamanca
Country [42] 0 0
Spain
State/province [42] 0 0
Sevilla
Country [43] 0 0
Spain
State/province [43] 0 0
Valencia
Country [44] 0 0
Sweden
State/province [44] 0 0
Göteborg
Country [45] 0 0
Sweden
State/province [45] 0 0
Lund
Country [46] 0 0
Sweden
State/province [46] 0 0
Stockholm
Country [47] 0 0
Turkey
State/province [47] 0 0
Istanbul
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Leeds
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Manchester
Country [50] 0 0
United Kingdom
State/province [50] 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/ct2/show/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
Contact-US@sanofi.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06143891