RecruitingPhase 2NCT06237335

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


Sponsor

ReCode Therapeutics

Enrollment

192 participants

Start Date

Feb 1, 2024

Study Type

INTERVENTIONAL

Conditions

Summary

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


Eligibility

Min Age: 18 YearsMax Age: 60 Years

Inclusion Criteria13

  • 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.
  • 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
  • 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

Exclusion Criteria14

  • 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.
  • 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
  • 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

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Interventions

DRUGRCT2100

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

OTHERPlacebo

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

DRUGRCT2100

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

DRUGRCT2100

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

DRUGIvacaftor

ivacaftor administered orally for 6 weeks

DRUGRCT2100

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(23)

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

King's College Hospital

London, United Kingdom

Nottingham University Hospitals

Nottingham, United Kingdom

University Hospital Southampton

Southampton, United Kingdom

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NCT06237335


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