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

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.

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.

Inclusion Criteria: * 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. Exclusion Criteria: * 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.