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

A regiszterben nem jelölt feltételek

• 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.