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NCT06237335PHASE2RecruitingAccepts Healthy Volunteers

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

ReCode Therapeutics

Start Date

2/1/2024

Completion Date

12/31/2026

Summary

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

Detailed Description

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).

Eligibility Criteria

Age Range: 18 years to 60 years

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.

Interventions

DRUG

RCT2100

OTHER

Placebo

DRUG

RCT2100

DRUG

RCT2100

DRUG

Ivacaftor

DRUG

RCT2100

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Conditions

Cystic Fibrosis

Locations

The University of Alabama at Birmingham

Birmingham, Alabama 35294

United States

University of Arizona

Tucson, Arizona 85719

United States

Stanford University

Palo Alto, California 94304

United States

UCSD

San Diego, California 92037

United States

National Jewish Health

Denver, Colorado 80206

United States

Emory University

Atlanta, Georgia 30322

United States

Boston Children's Hospital

Boston, Massachusetts 02215

United States

New York Medical College

Valhalla, New York 10595

United States

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27599

United States

Oregon Health & Science University

Portland, Oregon 97239

United States

University of Pittsburgh

Pittsburgh, Pennsylvania 15213

United States

UT Southwestern Medical Center

Dallas, Texas 75390

United States

University of Washington

Seattle, Washington 98195

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