Study to Evaluate the Safety & Tolerability of MRT5005 Administered by Nebulization in Adults With Cystic Fibrosis

A Phase 1/2, Randomized, Double-Blinded, Placebo-Controlled, Combined Single and Multiple Ascending Dose Study Evaluating the Safety, Tolerability, and Biological Activity of MRT5005 Administered by Nebulization to Adult Subjects With Cystic Fibrosis

This Phase 1/2, first-in-human study evaluated the safety and tolerability of single and multiple escalating doses of MRT5005 administered by nebulization to the respiratory tract of adult subjects with cystic fibrosis (CF).

Inclusion Criteria:

• Confirmed diagnosis of CF as defined by both of the following:

  • Two CF disease-causing cystic fibrosis transmembrane conductance regulator (CFTR) mutations in Class I or II (genotype confirmed at the screening visit).
  • Chronic sinopulmonary disease and/or gastrointestinal/nutritional abnormalities consistent with CF disease.

• Clinically stable CF disease, as judged by the investigator.

• Forced expiratory volume in 1 second (FEV1) ≥50% and ≤90% of the predicted normal for age, gender, and height at screening.

• Resting oxygen saturation ≥92% on room air (pulse oximetry).

Exclusion Criteria:

• An acute upper or lower respiratory infection, pulmonary exacerbation, or clinically significant episode of hemoptysis or change in chronic respiratory medications (including antibiotics) for CF lung disease within 28 days prior to dosing with investigational product on Day 1.
• Participants were receiving treatment with ivacaftor monotherapy (KALYDECO).
• Parts A and B only: Were receiving treatment with triple combination therapy (TRIKAFTA).
• Participants with a Class III, IV, or V CFTR gene mutation in at least 1 allele.
• Infection with highly virulent bacteria associated with accelerated decline in pulmonary function and/or decreased survival (e.g., Burkholderia cenocepacia, Burkholderia dolosa, Mycobacterium abscessus).

Treatment with ORKAMBI or SYMDEKO was not an exclusion for this study.