UAB - Center for Clinical and Translational Science

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

Purpose

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).

Condition

Cystic Fibrosis

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

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.

Study Design

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Part A - SAD Group 1: MRT5005 8 mg	Participants received single dose of MRT5005 8 milligrams (mg) by nebulization on Day 1.	Drug: MRT5005 Nebulization of MRT5005
Experimental Part A - SAD Group 2: MRT5005 16 mg	Participants received single dose of MRT5005 16 mg by nebulization on Day 1.	Drug: MRT5005 Nebulization of MRT5005
Experimental Part A - SAD Group 3: MRT5005 20 mg	Participants received single dose of MRT5005 20 mg by nebulization on Day 1.	Drug: MRT5005 Nebulization of MRT5005
Experimental Part A - SAD Group 4: MRT5005 24 mg	Participants received single dose of MRT5005 24 mg by nebulization on Day 1.	Drug: MRT5005 Nebulization of MRT5005
Placebo Comparator Part A - SAD Groups: Pooled Placebo	Participants received single dose of placebo (normal saline) by nebulization on Day 1. Data were analyzed as a pooled population for all participants who received placebo in Part A SAD groups and reported in this arm.	Drug: Normal saline Normal Saline for Inhalation
Experimental Part B - MAD Group 1: MRT5005 8 mg	Participants received MRT5005 8 mg once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29).	Drug: MRT5005 Nebulization of MRT5005
Experimental Part B - MAD Group 2: MRT5005 12 mg	Participants received MRT5005 12 mg once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29).	Drug: MRT5005 Nebulization of MRT5005
Experimental Part B - MAD Group 3: MRT5005 16 mg	Participants received MRT5005 16 mg once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29).	Drug: MRT5005 Nebulization of MRT5005
Experimental Part B - MAD Group 4: MRT5005 20 mg	Participants received MRT5005 20 mg once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29).	Drug: MRT5005 Nebulization of MRT5005
Placebo Comparator Part B - MAD Groups: Pooled Placebo	Participants received placebo (normal saline) once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29). Data were analyzed as a pooled population for all participants who received placebo in Part B MAD groups and reported in this arm.	Drug: Normal saline Normal Saline for Inhalation
Experimental Part D: MRT5005 4 mg	Participants received MRT5005 4 mg once daily by nebulization from Day 1 to Day 5.	Drug: MRT5005 Nebulization of MRT5005
Placebo Comparator Part D: Placebo	Participants received placebo (normal saline) once daily by nebulization from Day 1 to Day 5.	Drug: Normal saline Normal Saline for Inhalation

More Details

Status: Completed
Sponsor: Sanofi