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

HP-00091412

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.

2020-06-30

2024-06-30

2028-06-30

Withdrawn

Early phase I

Inclusion Criteria: 1. Age: 18 or older. 2. Recipient of a single or double pulmonary allograft at least twelve months before study entry. 3. Clinically diagnosed BOS grade 1 or 2 4. Receiving oral TAC-based immunosuppression according to institutional standards. 5. Capable of understanding the purposes and risks of the study, has given written informed consent and agrees to comply with the study requirements and capable of protocol adherence. 6. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study entry. 7. Stable to enable routine pre and post-transplant bronchoscopy with BAL and biopsy. 8. Fasting cholesterol \< 250 mg/dL, fasting triglycerides \< 250 mg/dL - Exclusion Criteria: 1. Active bacterial, viral or fungal infection not successfully resolved at least 4 weeks prior to study entry. 2. Mechanical ventilation. 3. At screening FEV1 \< 1 liter and/or \< FEV1 of 25 % predicted. 4. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy. 5. Women who breastfeed. 6. Known hypersensitivity to sirolimus. 7. Serum creatinine value of \> 2.5 mg/dL or chronic dialysis use or liver disease with a bilirubin \> 2 mg/dL. 8. Subjects with severe underlying disease other than BOS that is thought to become fatal within four months of clinical assessment. 9. Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to study entry. This is defined as any treatment that is implemented under an Investigational New Drug. 10. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures. 11. Any co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the patient's participation in the clinical trial. 12. Clinically significant bronchial strictures unresponsive to dilatation procedures. 13. Subjects with malignancy diagnosed within one year prior to screen (with the exception of skin cancers). 14. Lipid panel fasting cholesterol \> 250 mg/dL, fasting triglycerides \>250 mg/dL -

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2023-05-06