A Phase 2 Study Evaluating Safety and Tolerability of RCT2100 (CFTR mRNA) in Healthy Participants and in Participants With CF

This is the first-in-human study with RCT2100 and is designed to provide safety and tolerability data for future clinical studies.

This is a multi-part study to assess the safety, tolerability, and biodistribution of a single ascending dose of inhaled RCT2100 administered via nebulizer to healthy participants (Part 1), the safety and tolerability of multiple-ascending doses of inhaled RCT2100 administered to participants with CF (Part 2), and the safety and tolerability of RCT2100 co-administered with ivacaftor in participants with CF (Part 3).

Part 1 Major Inclusion Criteria: * Healthy, adult, male or female, 18-55 years of age, inclusive, at screening. * Body weight greater than or equal to 50 kg and body mass index (BMI) between 16-32 kg/m2, inclusive * The participant has a forced expiratory volume in one second (FEV1) of at least 80% predicted * The participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening. * Understands the study procedures in the informed consent form (ICF), and is willing and able to comply with the protocol. Part 1 Major Exclusion Criteria: * History or presence of clinically significant medical, surgical, clinical laboratory, or psychiatric condition or disease. * The participant has supine blood pressure (BP) \>150 mm Hg (systolic) or \>90 mm Hg (diastolic), following at least 5 minutes of supine rest. * The participant has abnormal clinical laboratory tests at screening, as assessed by the study-specific laboratory. * The participant is a smoker or has used nicotine or nicotine-containing products 6 weeks before the first dose of study drug. Former smokers with greater than 10 pack years of smoking history are excluded. Part 2 Major Inclusion Criteria: * Confirmed diagnosis of CF * Forced expiratory volume in 1 second ≥50% and ≤100% of predicted mean value for age, sex, and height * a) Not eligible for CFTR modulators based on having mutations of CFTR gene on both alleles that are not responsive to CFTR modulator therapy OR * b) Eligible for CFTR modulators (based on local prescribing information) but not using CFTR modulators due to intolerance or contraindications Part 2 Major Exclusion Criteria: * Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15) * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for sinopulmonary disease within 4 weeks before the first dose of study drug * Lung infection with organisms associated with a more rapid decline in pulmonary status * Arterial oxygen saturation on room air less than 94% at screening * Treatment with a CFTR modulator (Kalydeco, Trikafta, Symdeko, Orkambi, or Alyftrek) within 12 weeks of Screening Other protocol defined Inclusion/Exclusion criteria may apply. Part 3 Major Inclusion Criteria: * Confirmed diagnosis of CF * Forced expiratory volume in 1 second ≥50% and ≤100% of predicted mean value for age, sex, and height * a) Not eligible for CFTR modulators based on having mutations of CFTR gene on both alleles that are not responsive to CFTR modulator therapy OR * b) Eligible for dual or triple CFTR modulators (based on local prescribing information) but not using CFTR modulators due to intolerance or contraindications Part 3 Major Exclusion Criteria: * Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15) * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for sinopulmonary disease within 4 weeks before the first dose of study drug * Lung infection with organisms associated with a more rapid decline in pulmonary status * Arterial oxygen saturation on room air less than 94% at screening * Treatment with a CFTR modulator (Kalydeco, Trikafta, Symdeko, Orkambi, or Alyftrek) within 12 weeks of Screening Other protocol defined Inclusion/Exclusion criteria may apply.