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

Официальное название

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

Обзор

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

Подробное описание

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).

Вмешательства

• Препарат RCT2100
  RCT2100 supplied as varying dose strengths administered via oral inhalation using nebulizer
• Другое Placebo
  Placebo of similar volumes to experimental dose strengths administered via oral inhalation using nebulizer
• Препарат RCT2100
  RCT2100 supplied as varying dose strengths administered via oral inhalation using nebulizer for 4 weeks
• Препарат RCT2100
  RCT2100 supplied at a single dose strength administered via oral inhalation using nebulizer for 12 weeks
• Препарат Ivacaftor
  ivacaftor administered orally for 6 weeks
• Препарат 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

Первичные конечные точки

• Part 1: The number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs). [Срок оценки: From Baseline Through Day 29]
• Part 2: The number of participants with CF with AEs and SAEs. [Срок оценки: From Day 1 through Safety Follow-up, Week 24]
• Part 3: The number of participants with CF with AEs and SAEs. [Срок оценки: From Day 1 through Safety Follow-up, Week 24]

Критерии участия

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 13 центров

• The University of Alabama at Birmingham — Birmingham
• University of Arizona — Tucson
• Stanford University — Palo Alto
• UCSD — San Diego
• National Jewish Health — Denver
• Emory University — Atlanta
• Boston Children's Hospital — Boston
• New York Medical College — Valhalla
• … и ещё 5 центров

Великобритания · 6 центров

• University Hospitals Birmingham — Birmingham
• Royal Papworth Hospital — Cambridge
• Leeds Teaching Hospitals — Leeds
• King's College Hospital — London
• Nottingham University Hospitals — Nottingham
• University Hospital Southampton — Southampton

Франция · 2 центра

• Centre Hospitalier Régional Universitaire de Montpellier - Hôpital Arnaud de Villeneuve — Montpellier
• Hôpital Necker Enfants Malades — Paris

Нидерланды · 1 центр

• UMC Utrecht — Utrecht

Новая Зеландия · 1 центр

• New Zealand Clinical Research (Part 1 Only) — Auckland

Идентификаторы

NCT: NCT06237335 · RCT2100-101 · 2024-512169-15

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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