ORganoId GuIded N-of-1 (ORIGIN-1) Trial: A phase 4 study to investigate whether people with cystic fibrosis (CF) with rare cystic fibrosis transmembrane regulator (CFTR) mutations who have an in vitro response to Trikafta will also have a clinically meaningful response to Trikafta versus placebo

The ORIGIN-1 Trial is investigating whether a lab test using mini-organ models grown from a patient's own tissue (called organoids) can predict which people with rare forms of cystic fibrosis will respond to a powerful medication called Trikafta (elexacaftor/tezacaftor/ivacaftor). Trikafta has been life-changing for people with the most common cystic fibrosis mutation (F508del), but many people with rare mutations are not eligible for it — even though some of them might actually benefit. In this trial, participants with rare CF mutations will take Trikafta and a placebo in alternating cycles. Researchers will compare lung function and symptom changes during each phase, and cross-reference the results with how that person's mini-organ model responded in the lab. The hypothesis is that the lab test can accurately identify who will benefit from the real drug. You may be eligible if you are at least 6 years old, have cystic fibrosis without the F508del mutation, have lung function between 40% and 90% of expected, and have provided or are willing to provide a rectal biopsy for organoid testing. People who have had a lung transplant, have been on a CFTR modulator in the past month, or are pregnant are not eligible. If this approach works, it could open up access to life-changing treatment for many more people with CF.