Study to Evaluate the Safety & Tolerability of MRT5005 Administered by Nebulization in Adults With Cystic Fibrosis (RESTORE-CF)

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).

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: MRT5005; Drug: Normal saline

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • University of Indiana
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • University Hospitals
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A, B and D: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily had a causal relationship with the study treatment. A serious adverse event (SAE) was any untoward medical occurrence (whether considered to be related to study treatment or not) that at any dose: resulted in death; or was life-threatening; or required inpatient hospitalization or prolongation of existing hospitalization; or resulted in persistent or significant disability/incapacity; or was a congenital abnormality/birth defect; or was an important medical event. The TEAEs were defined as events that were newly reported or reported to worsen in severity after the start of study treatment up to 48 weeks (end of follow-up period) after the last dose of study treatment administration.	From the first dose of study treatment administration (Day 1) up to 48 weeks (end of the follow-up period) after the last dose of study treatment administration (Part A: Day 337, Part B: Day 365 and Part D: Day 341)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A, B and D: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	Spirometry was performed according to the guidelines published by the American Thoracic Society for standardization of spirometry. The ppFEV1 was assessed during the spirometry testing. For Parts A and B, the baseline value was defined as the average of the results from testing on Day -1 and at pre-dose on Day 1. For Part D, the baseline value was defined as the result from testing pre-dose on Day 1. Here, Baseline= BL, Day= D, pre-dose= PrD, hours post dose= hPD.	Part A:BL, D1(8hPD), D2(24hPD), D3, D8, D15 and D29; Part B:BL, D1(6hPD), D2, D8(PrD and 6hPD), D9, D15(PrD and 6hPD), D16, D22(PrD and 6hPD), D23, D29(PrD and 6hPD), D30, D36, D43 and D57; Part D:BL, D1(2hPD), PrD on D2, D3, D4 and D5, D11, D18 and D32

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2018
• Primary Completion (Actual): March 15, 2022
• Study Completion (Actual): March 15, 2022

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: December 11, 2017
• First Posted (Actual): December 15, 2017

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; CF
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Saline Solution
• Other Study ID Numbers: MRT5005-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No