NCT04415476

Standard Therapy Using Tacrolimus, Mycophenolate Mofetil and Prednisone For Chronic Lung Transplant Rejection (BOS)

A Randomized, Open-label,Controlled Phase II b Study to Demonstrate Efficacy and Safety of Sirolimus Chronic Rejection After Lung Transplant

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Maryland, Baltimore · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective single-center, open-label, randomized, controlled pilot study in the treatment of chronic rejection (CR), defined as grade 1 and 2 BOS, in adult recipients of a pulmonary allograft (single or double lungs).To assess the efficacy and safety of sirolimus plus tacrolimus and prednisone (S) compared to standard therapy (tacrolimus, mycophenolate mofetil (MMF) and prednisone) (ST) for chronic rejection, defined as grades 1 and 2 bronchiolitis obliterans syndrome (BOS); BOS defined as ≥ 20% decline from maximal post-transplant FEV1.

Detailed description

This is a prospective single-center, open-label, randomized, controlled pilot study in the treatment of chronic rejection (CR), defined as grade 1 and 2 BOS, in adult recipients of a pulmonary allograft (single or double lungs). Patients meeting entry criteria shall demonstrate a sustained decline in FEV1 having met stage 1 or 2 BOS. Patients randomized to the study arm, will be treated with Sirolimus (S) orally in place of MMF in addition to tacrolimus and prednisone compared to those patients randomized to defined ST alone (tacrolimus, MMF and prednisone). The trial duration will be approximately Primary endpoints will include: Efficacy failure between ST and S randomized group investigational treatment regimens will be determined at 96 weeks after the last patient is randomization and enrolled at approximately study year 2. The control arm will receive standard of care treatment (ST) and immunosuppression according to the University of Maryland lung transplant protocol. Efficacy failure will be defined as the combined end point of progression of BOS (defined as at least a 20 % decline from the initial randomization FEV1 value confirmed by two separate measurements three weeks apart or more) or re-transplantation or death. The co-primary end point of FEV1 and FVC changes to define functional stabilization in the S arm compared to ST is to be completed when the last patient randomized (patient #30) has been enrolled for 2 years as well. Efficacy of S is to be assessed using following parameters to determine its effect on lung function: 1. Forced expiratory volume in one second (FEV1) 2. Forced vital capacity (FVC) 3. FEF 25-75 Secondary endpoints will include: * General S tolerability * Incidence and severity of adverse events (AE) * Changes in clinical laboratory parameters from baseline after randomization * Changes in vital signs * Changes in physical examinations * Incidence of infections * Average maintenance doses of calcineurin inhibitors, antimetabolite agents, and corticosteroids * Number of courses of augmented immunosuppressants * Number and days of hospitalization * Incidence of malignancies * Overall mortality (including transplant-related mortality) * Retransplantation

Conditions

• Disorder Related to Lung Transplantation
• Chronic Rejection of Lung Transplant
• Decreased Immunologic Activity

Interventions

Type	Name	Description
DRUG	Assigned Interventions	This is a prospective single-center, open-label, randomized, controlled pilot study in the treatment of chronic rejection (CR), defined as grade 1 and 2 BOS, in adult recipients of a pulmonary allograft (single or double lungs). Patients meeting entry criteria shall demonstrate a sustained decline in FEV1 having met stage 1 or 2 BOS. Patients randomized to the study arm, will be treated with Sirolimus (S) orally in place of MMF in addition to tacrolimus and prednisone compared to those patients randomized to defined ST alone (tacrolimus, MMF and prednisone). The trial duration will be approximately 2 years for each subject randomized. Treatment compliance and safety will be monitored by clinic visits at 4-6 week intervals for the 2 year subject duration and will include standard physical examinations and monitoring of routine clinical and laboratory parameters including cause of hospitalizations and rate of adverse events including death in each group. T

Timeline

• Start date: 2020-06-30
• Primary completion: 2024-06-30
• Completion: 2028-06-30
• First posted: 2020-06-04
• Last updated: 2023-05-06

Regulatory

• FDA-regulated drug study