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

ReCode Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: Ivacaftor; Drug: RCT2100; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06237335

RCT2100-101

2024-512169-15 (EudraCT Number)

Details and patient eligibility

About

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

Full 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).

Enrollment: 192 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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192 participants in 5 patient groups, including a placebo group

RCT2100 (Part 1)

Experimental group

Description:

RCT2100 single dose

Treatment:

Drug: RCT2100

Drug: RCT2100

Drug: RCT2100

Drug: RCT2100

Placebo (Part 1)

Placebo Comparator group

Description:

Placebo single dose

Treatment:

Other: Placebo

RCT2100 (Part 2) 4 week

Experimental group

Description:

RCT2100 multiple dose

Treatment:

Drug: RCT2100

Drug: RCT2100

Drug: RCT2100

Drug: RCT2100

RCT2100 (Part 2) 12 week

Experimental group

Description:

RCT2100 multiple dose

Treatment:

Drug: RCT2100

Drug: RCT2100

Drug: RCT2100

Drug: RCT2100

Experimental: RCT2100 (Part 3) 6 week

Experimental group

Description:

RCT2100 multiple dose

Treatment:

Drug: RCT2100

Drug: RCT2100

Drug: RCT2100

Drug: Ivacaftor

Drug: RCT2100