ROCKnrol-1: 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.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Up to 5 years
Study Design
Arms and Interventions
| Arm | Intervention/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
Other Names:
Drug: Prednisone
Pharmaceutical form:Tablet-Route of administration:oral
Drug: Prednisolone
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
Drug: Prednisone
Pharmaceutical form:Tablet-Route of administration:oral
Drug: Prednisolone
Pharmaceutical form:Tablet-Route of administration:oral
|
Outcome Measures
Primary Outcome Measures
- Event-Free Survival (EFS) [Until the end of the study (up to 5 years since first patient in).]
from the date of randomization to the date of any predefined event, whichever occurs first
Secondary Outcome Measures
- modified Lee Symptom Scale (mLSS) [Until the end of the study (up to 5 years since first patient in).]
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)
- overall response rate (ORR) [Until the end of the study (up to 5 years since first patient in).]
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 months
- rate of corticosteroid withdrawal [Until the end of the study (up to 5 years since first patient in).]
Proportion 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 toxicity
- Overall response rate (ORR) [Until the end of the study (up to 5 years since first patient in).]
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 cGVHD
- ORR by 24 weeks [Until the end of the study (up to 5 years since first patient in).]
Proportion 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 cGVHD
- Duration of response (DOR) [Until the end of the study (up to 5 years since first patient in).]
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
- Dose reduction in corticosteroid [Until the end of the study (up to 5 years since first patient in).]
Proportion of participants with a reduction in daily corticosteroid dose
- Failure Free Survival (FFS) [Until the end of the study (up to 5 years since first patient in).]
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.
- Change in patient reported outcome (PRO) [Until the end of the study (up to 5 years since first patient in).]
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)
- Number of participants with treatment-emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs) [Until the end of the study (up to 5 years since first patient in).]
- Overall survival [Until the end of the study (up to 5 years since first patient in).]
The time from the date of randomization to the date of death due to any cause
Eligibility Criteria
Criteria
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:
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope Site Number : 8400001 | Duarte | California | United States | 91010 |
Sponsors and Collaborators
- Sanofi
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EFC17757
- 2023-505394-32
- U1111-1280-4918