Active, not recruiting
Phase 2
A Phase 2 Study Evaluating Safety and Tolerability of RCT2100 (CFTR mRNA) in Healthy Participants and in Participants With CF
Condition(s) studied
Cystic Fibrosis
Investigational drug(s) / intervention(s)
RCT2100PlaceboRCT2100RCT2100IvacaftorRCT2100
RCT2100: RCT2100 supplied as varying dose strengths administered via oral inhalation using nebulizer
Placebo: Placebo of similar volumes to experimental dose strengths administered via oral inhalation using nebulizer
RCT2100: RCT2100 supplied as varying dose strengths administered via oral inhalation using nebulizer for 4 weeks
RCT2100: RCT2100 supplied at a single dose strength administered via oral inhalation using nebulizer for 12 weeks
Ivacaftor: ivacaftor administered orally for 6 weeks
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
Study summary
This is the first-in-human study with RCT2100 and is designed to provide safety and tolerability data for future clinical studies.
Eligibility
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.
Primary outcome measure(s)
- Part 1: The number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs). — From Baseline Through Day 29
Safety and tolerability as assessed by number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Part 2: The number of participants with CF with AEs and SAEs. — From Day 1 through Safety Follow-up, Week 24
Safety and tolerability of multiple-ascending doses of inhaled RCT2100 administered to participants with CF
- Part 3: The number of participants with CF with AEs and SAEs. — From Day 1 through Safety Follow-up, Week 24
To assess the safety and tolerability of RCT2100 co-administered with ivacaftor in participants with CF.
Trial sites (23)
| Facility | City | Region | Status |
| The University of Alabama at Birmingham |
Birmingham |
Alabama |
|
| University of Arizona |
Tucson |
Arizona |
|
| Stanford University |
Palo Alto |
California |
|
| UCSD |
San Diego |
California |
|
| National Jewish Health |
Denver |
Colorado |
|
| Emory University |
Atlanta |
Georgia |
|
| Boston Children's Hospital |
Boston |
Massachusetts |
|
| New York Medical College |
Valhalla |
New York |
|
| The University of North Carolina at Chapel Hill |
Chapel Hill |
North Carolina |
|
| Oregon Health & Science University |
Portland |
Oregon |
|
| University of Pittsburgh |
Pittsburgh |
Pennsylvania |
|
| UT Southwestern Medical Center |
Dallas |
Texas |
|
| University of Washington |
Seattle |
Washington |
|
| 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 |
|
| King's College Hospital |
London |
United Kingdom |
|
| Nottingham University Hospitals |
Nottingham |
United Kingdom |
|
| University Hospital Southampton |
Southampton |
United Kingdom |
|
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