Targeting Interferon Gamma With Emapalumab to Lung Transplant Recipients With Interferon Gamma-high Acute Lung Allograft Dysfunction

Обзор

This study is testing a medication called emapalumab to see if it can help people who have had a lung transplant and are experiencing a sudden drop in lung function, called acute lung allograft dysfunction (ALAD). ALAD is a serious condition that can happen after a lung transplant and can lead to worsening breathing and other complications. Right now, there is no approved treatment for ALAD. The main goal is to see if lung function improves, meaning it returns close to your usual (baseline) level within 90 days.

Подробное описание

You may be able to join if:

You had a lung transplant more than 10 months ago, and Your lung function has dropped by 10% or more compared to your best level in the past 6 months.

What will happen in the study?

As part of your usual care, you will have a procedure called a bronchoscopy (a test that looks inside your lungs). During this test, doctors will collect samples to check for infection and measure certain markers in your lungs and blood.

These results will help determine if you can join the study.

People with certain lung infections will not be able to participate.

Study treatment

The study has two parts:

Part 1 (finding the right dose):

Small groups of participants will receive different doses of emapalumab through an IV (into a vein). The goal is to find the dose that best blocks harmful inflammation in the lungs.

Part 2 (testing how well it works):

Participants will receive the selected dose of emapalumab. Doctors will:

Monitor blood and lung markers, Check for viruses, Follow your progress weekly for about 4 weeks.

Study goals:

The main goal is to see if lung function improves, meaning it returns close to your usual (baseline) level within 90 days.

The study will also look at:

Whether the condition gets worse or improves, How safe the treatment is, Overall outcomes after treatment.

Вмешательства

• Препарат Emapalumab
  This is a one-time infusion
• Препарат Placebo
  This is a one-time infusion of inactive drug

Первичные конечные точки

• Recovery from Acute Lung Allograft Dysfunction, defined by International Society for Heart and Lung Transplantation guidelines as a return to within 10% of baseline FEV1 within 90 days [Срок оценки: 90 days]

Вторичные конечные точки (1)

• CXCL9 area under the curve (AUC), safety outcomes and retransplant-free survival will be used to measure ALAD Progression [Срок оценки: 90 days]

Критерии участия

Критерии включения

• Recipients ≥10 months post-lung transplant who are enrolled in existing biorepository study (IRB #13-10738) will be approached if they have ALAD and elevated AI2 and CXCL9 levels
• Age: ≥18 years old
• Informed Consent: Ability to provide written informed consent to participate in the study.

Критерии исключения

• Active Bacterial Infection: Positive bacterial cultures from bronchoalveolar lavage (BAL) samples at the time of ALAD diagnosis. Viral infections, which are typically treated in lung transplant recipients with a steroid taper and cleared by type I interferons, are not exclusion criteria per se.
• Active CMV or EBV Infection: Active reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV) based on plasma PCR testing.
• Severe Comorbidities: Presence of severe conditions likely to compromise study participation or outcomes (e.g., terminal illness).
• Pregnancy or Breastfeeding: Women who are pregnant or breastfeeding at the time of screening.
• Concurrent Immunosuppressive Therapy Trials: Use of investigational agents or therapies other than standard of care post-transplant immunosuppression.
• Allergy to Study Drug: Known hypersensitivity to emapalumab or any of its components.
• Insufficient Baseline Data: Lack of prior baseline FEV1 data for comparison.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• University of California, Los Angeles — Los Angeles
• University of California, San Francisco — San Francisco

Публикации

• Herlong HF, Maddrey WC, Walser M. The use of ornithine salts of branched-chain ketoacids in portal-systemic encephalopathy. Ann Intern Med. 1980 Oct;93(4):545-50. doi: 10.7326/0003-4819-93-4-545. PMID 7001971
• Concepcion J, Marti M, Vehar S, Corbitt K. Refractory MDA-5 dermatomyositis rapidly progressive interstitial lung disease successfully treated with emapalumab. Ann Rheum Dis. 2025 May;84(5):879-880. doi: 10.1016/j.ard.2025.01.010. Epub 2025 Jan 31. No abstract available. PMID 39893100
• Liu G, Qian S, Liu J, Ma H, Wang Q. Efficacy of emapalumab in treating 3 pediatric patients with epstein-barr virus-associated hemophagocytic lymphohistiocytosis complicated by multiple organ dysfunction. Ann Med. 2025 Dec;57(1):2569991. doi: 10.1080/07853890.2025.2569991. Epub 2025 Oct 9. PMID 41066671
• Shino MY, Todd JL, Neely ML, Kirchner J, Frankel CW, Snyder LD, Pavlisko EN, Fishbein GA, Schaenman JM, Mason K, Kesler K, Martinu T, Singer LG, Tsuang W, Budev M, Shah PD, Reynolds JM, Williams N, Robien MA, Palmer SM, Weigt SS, Belperio JA. Plasma CXCL9 and CXCL10 at allograft injury predict chronic lung allograft dysfunction. Am J Transplant. 2022 Sep;22(9):2169-2179. doi: 10.1111/ajt.17108. Ep PMID 35634722
• Groom JR, Luster AD. CXCR3 in T cell function. Exp Cell Res. 2011 Mar 10;317(5):620-31. doi: 10.1016/j.yexcr.2010.12.017. PMID 21376175
• Feng H, Zhang YB, Gui JF, Lemon SM, Yamane D. Interferon regulatory factor 1 (IRF1) and anti-pathogen innate immune responses. PLoS Pathog. 2021 Jan 21;17(1):e1009220. doi: 10.1371/journal.ppat.1009220. eCollection 2021 Jan. PMID 33476326
• Tellides G, Pober JS. Interferon-gamma axis in graft arteriosclerosis. Circ Res. 2007 Mar 16;100(5):622-32. doi: 10.1161/01.RES.0000258861.72279.29. PMID 17363708
• Zhang H, Zhang D, Xu Y, Zhang H, Zhang Z, Hu X. Interferon-gamma and its response are determinants of antibody-mediated rejection and clinical outcomes in patients after renal transplantation. Genes Immun. 2024 Feb;25(1):66-81. doi: 10.1038/s41435-024-00254-x. Epub 2024 Jan 22. PMID 38246974

Идентификаторы

NCT: NCT07538336 · 25-45438

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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