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

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

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: RCT2100; Other: Placebo; Drug: RCT2100; Drug: RCT2100; Drug: RCT2100; Drug: Ivacaftor

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).

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Priya Ryali, MBA; Phone Number: 650-629-7900; Email: clinicaltrials@recodetx.com

Study Locations

• France
  • Montpellier, France
    • Recruiting
    • Centre Hospitalier Régional Universitaire de Montpellier - Hôpital Arnaud de Villeneuve
  • Paris, France
    • Recruiting
    • Hopital Necker Enfants Malades
• Netherlands
  • Utrecht, Netherlands
    • Recruiting
    • UMC Utrecht
• New Zealand
  • Auckland, New Zealand
    • Completed
    • New Zealand Clinical Research (Part 1 Only)
• United Kingdom
  • Birmingham, United Kingdom
    • Recruiting
    • University Hospitals Birmingham
  • Cambridge, United Kingdom
    • Recruiting
    • Royal Papworth Hospital
  • Leeds, United Kingdom
    • Recruiting
    • Leeds Teaching Hospitals
  • London, United Kingdom
    • Recruiting
    • King's College Hospital
  • Nottingham, United Kingdom
    • Recruiting
    • Nottingham University Hospitals
  • Southampton, United Kingdom
    • Recruiting
    • University Hospital Southampton
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • The University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Recruiting
      • University of Arizona
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
    • San Diego, California, United States, 92037
      • Recruiting
      • UCSD
  • Colorado
    • Denver, Colorado, United States, 80206
      • Recruiting
      • National Jewish Health
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Boston Children's Hospital
  • New York
    • Valhalla, New York, United States, 10595
      • Recruiting
      • New York Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • The University of North Carolina at Chapel Hill
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RCT2100 (Part 1); RCT2100 single dose	Drug: RCT2100; RCT2100 supplied as varying 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: 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
Placebo Comparator: Placebo (Part 1); Placebo single dose	Other: Placebo; Placebo of similar volumes to experimental dose strengths administered via oral inhalation using nebulizer
Experimental: RCT2100 (Part 2) 4 week; RCT2100 multiple dose	Drug: RCT2100; RCT2100 supplied as varying 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: 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
Experimental: RCT2100 (Part 2) 12 week; RCT2100 multiple dose	Drug: RCT2100; RCT2100 supplied as varying 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: 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
Experimental: Experimental: RCT2100 (Part 3) 6 week; RCT2100 multiple dose	Drug: RCT2100; RCT2100 supplied as varying 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: 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; Drug: Ivacaftor; ivacaftor administered orally for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: The number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs).	Safety and tolerability as assessed by number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Baseline Through Day 29
Part 2: The number of participants with CF with AEs and SAEs.	Safety and tolerability of multiple-ascending doses of inhaled RCT2100 administered to participants with CF	From Day 1 through Safety Follow-up, Week 24
Part 3: The number of participants with CF with AEs and SAEs.	To assess the safety and tolerability of RCT2100 co-administered with ivacaftor in participants with CF.	From Day 1 through Safety Follow-up, Week 24

Collaborators and Investigators

• Sponsor: ReCode Therapeutics
• Investigators: Study Chair: John Matthews, MBBS, MCRP, PhD, ReCode Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Actual): February 1, 2024

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; mRNA; CF
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis; ivacaftor
• Other Study ID Numbers: RCT2100-101; 2024-512169-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No