A Study to Test How Effective Belumosudil Tablets Are for Treating Adult Participants With Chronic Lung Allograft Dysfunction (ROCKaspire)

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study, Followed by Open-label Extensions, to Evaluate the Efficacy of Oral Belumosudil in Adult Participants With Chronic Lung Allograft Dysfunction (CLAD) Following Bilateral Lung Transplantation

This double-blind, randomized, placebo-controlled, multinational, multicenter, parallel-group, Phase 3, 2-arm, study will investigate the efficacy and safety of belumosudil compared with placebo, both administered on top of azithromycin and standard-of-care regimen of immunosuppression in male or female participants at least 1 year after bilateral lung transplant, who are at least 18 years of age and who have evidence of progressive CLAD despite azithromycin therapy.

Study details include:

The study duration will be up to 31 weeks for participants not entering the open-label extension (OLE) period and up to 57 weeks for participants entering the OLE period but not the long-term OLE.

The treatment duration will be up to 26 weeks for participants not entering the OLE period and up to 52 weeks for participants entering the OLE period but not the long-term OLE.

The number of visits will be up to 10 visits for participants not entering the OLE period and up to 16 visits for participants entering the OLE period but not the long-term OLE.

For participants who enter the long-term OLE, treatment and study participation will continue with visits every 12 weeks per protocol specifications.

Study Overview

• Status: Recruiting
• Conditions: Lung Transplant Rejection
• Intervention / Treatment: Drug: Belumosudil; Drug: Azithromycin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free number for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Belgium
  • Godinne, Belgium, B-5530
    • Recruiting
    • Investigational Site Number : 0560002
  • Leuven, Belgium, 3000
    • Recruiting
    • Investigational Site Number : 0560001
• Finland
  • Helsinki, Finland, 00290
    • Recruiting
    • Investigational Site Number : 2460001
• France
  • Marseille, France, 13015
    • Recruiting
    • Investigational Site Number : 2500006
• Hungary
  • Budapest, Hungary, 1083
    • Recruiting
    • Investigational Site Number : 3480001
• Israel
  • Petah-Tikva, Israel, 49100
    • Recruiting
    • Investigational Site Number : 3760001
• Italy
  • Milano, Italy, 20122
    • Recruiting
    • Investigational Site Number : 3800001
  • Palermo, Italy, 90133
    • Recruiting
    • Investigational Site Number : 3800004
  • Pavia, Italy, 27100
    • Recruiting
    • Investigational Site Number : 3800003
  • Siena, Italy, 53100
    • Recruiting
    • Investigational Site Number : 3800002
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • Investigational Site Number : 5280001
• Spain
  • Valencia, Spain, 46026
    • Recruiting
    • Investigational Site Number : 7240004
  • A Coruña [La Coruña]
    • La Coruña, A Coruña [La Coruña], Spain, 15006
      • Recruiting
      • Investigational Site Number : 7240002
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Recruiting
      • Investigational Site Number : 7240003
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • Investigational Site Number : 7240001
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • UAB Lung Health Center Site Number : 8400026
  • Florida
    • Orlando, Florida, United States, 32804
      • Recruiting
      • Advent Health Transplant Institute Site Number : 8400023
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland School of Medicine Site Number : 8400009
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5000
      • Recruiting
      • University of Michigan Hospital - 1500 E Medical Center Dr Site Number : 8400014
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine - Division of Pulmonary & Critical Care Medicine Site Number : 8400012
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • New York Presbyterian/Columbia University Medical Center Site Number : 8400002
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Recruiting
      • Temple University Hospital Site Number : 8400007
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor University Medical Center - Dallas Site Number : 8400011
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Research Institute Site Number : 8400021

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant ≥1 year post bilateral lung transplantation at the time of screening
• Participants presenting with CLAD
• Participants who have received at least 8 weeks of azithromycin

Exclusion Criteria:

• Lung function decline that can be explained by non-CLAD causes including but not limited to acute lung allograft rejection (>A1), antibody-mediated rejection within 4 weeks of screening, airway stenosis, or tracheobronchomalacia
• Participants who have received other treatments for CLAD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belumosudil + Azithromycin; Participants will receive 200 mg belumosudil orally once daily	Drug: Belumosudil; Tablet, Oral; Other Names: REZUROCK; Drug: Azithromycin; Tablet, Oral
Placebo Comparator: Placebo + Azithromycin; Participants will receive placebo orally once daily	Drug: Azithromycin; Tablet, Oral; Drug: Placebo; Tablet, Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline to Week 26 in forced expiratory volume in 1 second (FEV1)	Baseline to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate at Week 26	Defined as the proportion of participants with ≤10% decline in FEV1 at Week 26 compared with baseline	Baseline to Week 26
Absolute change from baseline to Week 26 in FEV1		Baseline to Week 26
Absolute change from baseline to Week 26 in percent predicted FEV1		Baseline to Week 26
Percent change from baseline to Week 26 in forced vital capacity (FVC)		Baseline to Week 26
Absolute change from baseline to Week 26 in FVC		Baseline to Week 26
Absolute change from baseline to Week 26 in percent predicted FVC		Baseline to Week 26
Percent change from baseline to Week 26 in total lung capacity (TLC)		Baseline to Week 26
Time to CLAD progression during the double-blind treatment period	Defined as the first of the following events: >10% decline in FEV1 compared with baseline, or change in CLAD stage, or re-transplantation, or death	Baseline to Week 26
Time to re-transplantation or death		Up to 7 days after the administration of last dose of study drug
Percent change from baseline to Week 26 in 6-minute walk distance		Baseline to Week 26
Absolute change from baseline to Week 26 in 6-minute walk distance		Baseline to Week 26
Absolute change from baseline to Week 26 in 6-minute walk nadir oxygen saturation		Baseline to Week 26
Change from baseline to Week 26 in Saint George Respiratory Questionnaire (SGRQ)	Total score and scores by domain	Baseline to Week 26
Change from baseline to Week 26 in EQ-5D-5L	Visual analogue scale and individual dimensions	Baseline to Week 26
Change from baseline to Week 26 in Patient-Reported Outcomes Measurement Information System-29 profile version 2.1	Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) profile V2.1 (domain scores)	Baseline to Week 26
Number of participants with adverse events (AEs) and serious adverse events (SAEs)	Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), as well as laboratory abnormalities during the double-blind treatment period and the open-label extensions	Up to 7 days after the administration of last dose of study drug

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Estimated): September 17, 2026
• Study Completion (Estimated): June 2, 2028

Study Registration Dates

• First Submitted: October 7, 2023
• First Submitted That Met QC Criteria: October 7, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Azithromycin; Belumosudil
• Other Study ID Numbers: EFC17801; U1111-1280-6777 (Registry Identifier: ICTRP); 2023-503462-23 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No