Organoid-Guided drug trial offers hope for cystic fibrosis patients with rare mutations

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: A subject must meet ALL the following criteria in order to participate: 1. Male or female subjects who completed the HIT-CF Organoid Study and are 18 years of age or older on the date of informed consent 2. Confirmed diagnosis of CF as follows: * Sweat chloride value of ≥60 mmol/L based on quantitative pilocarpine iontophoresis (at screening) OR 2 CF-causing mutations AND * chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities 3. Clinically stable CF disease in the opinion of the investigator with no significant changes in health status within 28 days prior to Day 1 4. Forced expiratory volume in one second (FEV1) ≥40% of predicted to ≤90% of predicted at the Screening Visit, based on the Global Lung Function Initiative (GLI) -2012 multi-ethnic all-age reference equations 5. Body mass index (BMI) ≥16 kg/m2 and ≤30 kg/m2 6. Non-smoker and non-tobacco user (including all inhalational nicotine delivery systems) for a minimum of 30 days prior to screening, and subject agrees not to smoke or use tobacco for the duration of the study 7. Subjects of childbearing potential must meet contraception requirements (Section 13.3.1) 8. Willing to remain on a stable medication regimen for CF from 28 days before Day 1 through the last study visit 9. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, and other study procedures 10. Selected by an unblinded coordinating team based on organoid response or random selection 11. Subject will sign and date an informed consent form (ICF Exclusion Criteria: A subject who meets ANY of the following criteria will be excluded from participation: 1. Subject has at least one of the following CFTR-mutations: F508del, G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, R117H, A455E, 3849+10kbC\>T OR A combination of any two of the following mutations: any nonsense mutation, 1717-1G\>A, 621+1G\>T, 3120+1G\>A, 1898+1G-\>A, CFTRdele2,3, and 2183AA-\>G 2. History or current evidence of any clinically significant cardiac (eg, heart failure, left ventricular hypertrophy, myocardial infarction, and arrhythmia), endocrinologic, hematologic, hepatobiliary (eg, clinically significant cirrhosis with or without portal hypertension, hepatitis B or hepatitis C), immunologic, metabolic, urologic, pulmonary (besides CF), neurologic (eg, subarachnoid haemorrhage, intracranial haemorrhage, cerebrovascular accident, intracranial trauma, and autonomic neuropathy), dermatologic, psychiatric, renal, or other major disease, that is unstable or could interfere with the subject's participation in or completion of the study, in the opinion of the investigator 3. Clinically significant screening results that would exclude subject from the study (eg, medical history, physical examination, ECG, vital sign, pulse oximetry, and laboratory profiles) or any conditions that, would make the subject unsuitable for enrolment or could interfere with the subject's participation in or completion of the study, in the opinion of the investigator. The medical monitor must be contacted for review of any subjects with screening results or conditions that may make them unsuitable for enrolment or could interfere with participation in or completion of the study. 4. Prolonged QTcF \>450 msec at screening 5. Abnormal liver function as defined by AST, ALT, gamma-glutamyl transferase (GGT), or alkaline phosphatase ≥3 times or total bilirubin ≥2 times upper limit of the normal range 6. Haemoglobin \<10 g/dL 7. Platelet count \<150,000 cells/mm3 8. Abnormal renal function at screening defined as creatinine clearance \<60 mL/min using the Modified Diet in Renal Disease (MDRD) 9. Hospitalisation, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (in the opinion of the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 28 days of Day 1 10. Lung infection with organisms associated with a more rapid decline in pulmonary status (eg, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). Subjects who have a current or past history of a positive culture must be reviewed with the medical monitor to confirm clinical stability. 11. Subject is currently taking or has taken a CFTR modulator within 28 days prior to Day 1 12. Participation in another clinical trial or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to screening. The duration of the elapsed time may be longer if required by local regulations 13. History of cancer (excluding cervical carcinoma in situ and non-melanoma skin cancer with curative therapy for at least 5 years prior to screening) 14. History of organ or hematologic transplantation 15. History or current evidence of alcohol or drug abuse or dependence within 12 months of screening, in the opinion of the investigator 16. Initiation of any new chronic therapy (eg, ibuprofen, hypertonic saline, azithromycin, dornase alfa, aztreonam for inhalation solution, and tobramycin) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1 17. Known or suspected hypersensitivity or idiosyncratic reaction to the study drugs or any components thereof 18. Pregnant or nursing women 19. Special or vulnerable status (e.g. institutionalized, or person related to or an employee of the sponsor, FAIR Therapeutics, or investigator)