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

Phase 1/2

Recruiting

Conditions: Cystic Fibrosis

Interventions: Drug: RCT2100
Other: Placebo

Registration Number: 2024-512169-15-00

Lead Sponsor: Recode Therapeutics Inc.

Brief Summary: To assess the safety and tolerability of multiple-ascending doses of inhaled RCT2100 administered via nebulizer to participants with CF

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) and multiple-ascending doses of inhaled RCT2100 administered to participants with CF (Part 2).

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

Males or females aged 18 years or older on the date of informed consent

Confirmed diagnosis of CF

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

Forced expiratory volume in 1 second ≥40% and ≤100% of predicted mean value for age, sex, and height (equations of the Global Lung Function Initiative [GLI]) at the Screening Visit. Spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria for acceptability and repeatability

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 (Day 1)

Lung infection with organisms associated with a more rapid decline in pulmonary status (including, but not limited to, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). For participants who have had a history of a positive culture, the Investigator will apply the following criteria to establish whether the participant is free of infection from such organisms: • The participant has not had a respiratory tract culture positive for these organisms within the 12 months before the date of informed consent • The participant has had at least two respiratory tract cultures negative for such organisms within the 12 months before the date of informed consent, with the first and last of these separated by at least 3 months, and the most recent one within the 6 months before the date of informed consent

Arterial oxygen saturation on room air less than 94% at screening

Values of AST, ALT, alkaline phosphatase or gamma-glutamyl transferase (GGT) ≥3×ULN

Estimated glomerular filtration rate < 30 mL/minute/1.73 m2 calculated with the Chronic Kidney Disease Epidemiology Collaboration formula

Treatment with a CFTR modulator (Eg. Kalydeco, Trikafta, Symdeko, or Orkambi) within 12 weeks of Screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RCT2100 (Part 1)	RCT2100	RCT2100 single dose
Placebo (Part 1)	Placebo	Placebo single dose
RCT2100 (Part 2) 4 week	RCT2100	RCT2100 multiple dose
RCT2100 (Part 2) 12 week	RCT2100	RCT2100 multiple dose

Primary Outcome Measures

Name	Time	Method
Safety and tolerability as assessed by number of participants with AEs and SAEs		Safety and tolerability as assessed by number of participants with AEs and SAEs

Secondary Outcome Measures

Name	Time	Method
Biodistribution parameters may be derived from concentrations of RCT2100 components in blood (where feasible). Parameters may include but are not limited to the following: AUC, Cmax, Tmax, and t1/2		Biodistribution parameters may be derived from concentrations of RCT2100 components in blood (where feasible). Parameters may include but are not limited to the following: AUC, Cmax, Tmax, and t1/2
Absolute change in percent predicted FEV1 (ppFEV1) from baseline to Week 4 (escalation cohorts 1 to 3) or Week 12 (expansion cohort)		Absolute change in percent predicted FEV1 (ppFEV1) from baseline to Week 4 (escalation cohorts 1 to 3) or Week 12 (expansion cohort)
Change from baseline in CF questionnaire-revised (CFQ-R) respiratory domain score through Week 4 (escalation cohorts 1 to 3) or Week 12 (expansion cohort)		Change from baseline in CF questionnaire-revised (CFQ-R) respiratory domain score through Week 4 (escalation cohorts 1 to 3) or Week 12 (expansion cohort)
Incidence and titer of anti-CFTR binding antibodies		Incidence and titer of anti-CFTR binding antibodies
Based on safety and tolerability at projected efficacious doses		Based on safety and tolerability at projected efficacious doses

Trial Locations

Locations (4): Universitair Medisch Centrum Utrecht
🇳🇱
Utrecht, Netherlands
Centre Hospitalier Universitaire De Montpellier
🇫🇷
Montpellier, France
Hopital Necker Enfants Malades
🇫🇷
Paris, France
Centre Hospitalier Universitaire De Toulouse
🇫🇷
Toulouse, France
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Kors van der Ent
Site contact
0031302504944
k.vanderent@umcutrecht.nl