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

NCT03375047 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: MRT5005-101
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 16

Brief Summary

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).

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; CF

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Parts A, B and D: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

  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

Study Arms (12)

Part A - SAD Group 1: MRT5005 8 mg

EXPERIMENTAL

Participants received single dose of MRT5005 8 milligrams (mg) by nebulization on Day 1.

Drug: MRT5005

Part A - SAD Group 2: MRT5005 16 mg

EXPERIMENTAL

Participants received single dose of MRT5005 16 mg by nebulization on Day 1.

Drug: MRT5005

Part A - SAD Group 3: MRT5005 20 mg

EXPERIMENTAL

Participants received single dose of MRT5005 20 mg by nebulization on Day 1.

Drug: MRT5005

Part A - SAD Group 4: MRT5005 24 mg

EXPERIMENTAL

Participants received single dose of MRT5005 24 mg by nebulization on Day 1.

Drug: MRT5005

Part A - SAD Groups: Pooled Placebo

PLACEBO COMPARATOR

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

Part B - MAD Group 1: MRT5005 8 mg

EXPERIMENTAL

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

Part B - MAD Group 2: MRT5005 12 mg

EXPERIMENTAL

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

Part B - MAD Group 3: MRT5005 16 mg

EXPERIMENTAL

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

Part B - MAD Group 4: MRT5005 20 mg

EXPERIMENTAL

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

Part B - MAD Groups: Pooled Placebo

PLACEBO COMPARATOR

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

Part D: MRT5005 4 mg

EXPERIMENTAL

Participants received MRT5005 4 mg once daily by nebulization from Day 1 to Day 5.

Drug: MRT5005

Part D: Placebo

PLACEBO COMPARATOR

Participants received placebo (normal saline) once daily by nebulization from Day 1 to Day 5.

Drug: Normal saline

Interventions

MRT5005 DRUG

Nebulization of MRT5005

Part A - SAD Group 1: MRT5005 8 mg; Part A - SAD Group 2: MRT5005 16 mg; Part A - SAD Group 3: MRT5005 20 mg; Part A - SAD Group 4: MRT5005 24 mg; Part B - MAD Group 1: MRT5005 8 mg; Part B - MAD Group 2: MRT5005 12 mg; Part B - MAD Group 3: MRT5005 16 mg; Part B - MAD Group 4: MRT5005 20 mg; Part D: MRT5005 4 mg

Normal saline DRUG

Normal Saline for Inhalation

Part A - SAD Groups: Pooled Placebo; Part B - MAD Groups: Pooled Placebo; Part D: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Sanofi: lead

Study Sites (16)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Indiana

Indianapolis, Indiana, 46202, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

University Hospitals

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• 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.

  PMID: 31215818 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: December 15, 2017
• Study Start: May 10, 2018
• Primary Completion: March 15, 2022
• Study Completion: March 15, 2022
• Last Updated: February 9, 2026
• Results First Posted: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (16)