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RECRUITINGPhase 2INTERVENTIONAL

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

A Phase 1/2, Multicenter Study Evaluating the Safety, Tolerability, and Biodistribution of RCT2100 With Single-Ascending Doses in Healthy Participants and Multiple-Ascending Doses and Proof-of-Concept in Participants With Cystic Fibrosis

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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

Who May Be Eligible (Plain English)

Part 1 Major Who May Qualify: - 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 willing to sign a consent form form (ICF), and is willing and able to comply with the protocol. Part 1 Major Who Should NOT Join This Trial: - 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 Who May Qualify: - 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 Who Should NOT Join This Trial: - Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15) ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

DRUG

RCT2100

RCT2100 supplied as varying dose strengths administered via oral inhalation using nebulizer

OTHER

Placebo

Placebo of similar volumes to experimental dose strengths administered via oral inhalation using nebulizer

DRUG

RCT2100

RCT2100 supplied as varying dose strengths administered via oral inhalation using nebulizer for 4 weeks

DRUG

RCT2100

RCT2100 supplied at a single dose strength administered via oral inhalation using nebulizer for 12 weeks

DRUG

Ivacaftor

ivacaftor administered orally for 6 weeks

DRUG

RCT2100

RCT2100 supplied at varying dose strengths. Co- administered via oral inhalation using nebulizer for 4 weeks with ivacaftor after initial 2 weeks of ivacaftor dosing run in period

Locations (20)

The University of Alabama at Birmingham
Birmingham, Alabama, United States
University of Arizona
Tucson, Arizona, United States
Stanford University
Palo Alto, California, United States
UCSD
San Diego, California, United States
National Jewish Health
Denver, Colorado, United States
Emory University
Atlanta, Georgia, United States
Boston Children's Hospital
Boston, Massachusetts, United States
New York Medical College
Valhalla, New York, United States
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Oregon Health & Science University
Portland, Oregon, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
UT Southwestern Medical Center
Dallas, Texas, United States
University of Washington
Seattle, Washington, United States
Centre Hospitalier Régional Universitaire de Montpellier - Hôpital Arnaud de Villeneuve
Montpellier, France
Hôpital Necker Enfants Malades
Paris, France
UMC Utrecht
Utrecht, Netherlands
New Zealand Clinical Research (Part 1 Only)
Auckland, New Zealand
University Hospitals Birmingham
Birmingham, United Kingdom
Royal Papworth Hospital
Cambridge, United Kingdom
Leeds Teaching Hospitals
Leeds, United Kingdom