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 will evaluate the safety and tolerability of single and multiple escalating doses of MRT5005 administered by nebulization to the respiratory tract of adult subjects with CF.

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
  • Colorado
    • Denver, Colorado, United States, 80206
      • Recruiting
      • National Jewish Health
  • Florida
    • Gainesville, Florida, United States, 32608
      • Recruiting
      • University of Florida
    • Orlando, Florida, United States, 32803
      • Completed
      • Central Florida Pulmonary Group
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • University of Indiana
  • Maine
    • Portland, Maine, United States, 04102
      • Recruiting
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Recruiting
      • Johns Hopkins University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • UPMC Children's Hospital of Pittsburgh
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Completed
      • New Orleans Center for Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Recruiting
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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

  • Two CF disease-causing 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.
• 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, 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.
• Receiving treatment with ivacaftor monotherapy (KALYDECO)
• For all groups except Daily dosing: Receiving treatment with triple combination therapy (TRIKAFTA).
• Subjects 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 is 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

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose; 8 mg MRT5005	Drug: MRT5005; Nebulization of MRT5005
Experimental: Low/Mid Dose; 12 mg MRT5005	Drug: MRT5005; Nebulization of MRT5005
Experimental: Mid Dose; 16 mg MRT5005	Drug: MRT5005; Nebulization of MRT5005
Experimental: Mid/High Dose; 20 mg MRT5005	Drug: MRT5005; Nebulization of MRT5005
Experimental: High Dose; 24 mg MRT5005	Drug: MRT5005; Nebulization of MRT5005
Placebo Comparator: Placebo Comparator; Normal Saline 0.9% USP	Drug: Normal saline; Normal Saline for Inhalation
Experimental: Daily Dose; 20 mg MRT5005 delivered in 5 consecutive daily doses of 4mg	Drug: MRT5005; Nebulization of MRT5005

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Types, frequency and severity of treatment-emergent Adverse Events	Safety and tolerability of nebulized MRT5005 will be assessed through the types, frequency and severity of treatment-emergent Adverse Events experienced by participants on the trial	12 months after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biological activity of nebulized MRT5005	Changes from baseline in ppFEV1	4 weeks after last dose

Collaborators and Investigators

• Sponsor: Translate Bio, Inc.

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 (Anticipated): October 1, 2021
• Study Completion (Anticipated): December 1, 2021

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): November 16, 2020
• Last Update Submitted That Met QC Criteria: November 12, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; CF
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: MRT5005-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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