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

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ClinicalTrials.gov Identifier: NCT03375047
Recruitment Status : Recruiting
First Posted : December 15, 2017
Last Update Posted : November 16, 2020
Sponsor:
Information provided by (Responsible Party):
Translate Bio, Inc.

Tracking Information
First Submitted Date  ICMJE September 7, 2017
First Posted Date  ICMJE December 15, 2017
Last Update Posted Date November 16, 2020
Actual Study Start Date  ICMJE May 10, 2018
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
Types, frequency and severity of treatment-emergent Adverse Events [ Time Frame: 12 months after last dose ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2020)
Biological activity of nebulized MRT5005 [ Time Frame: 4 weeks after last dose ]
Changes from baseline in ppFEV1
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
Delivery of mRNA [ Time Frame: 24 hours after 5th dose ]
Assessment of delivery of the mRNA to the bronchial epithelial cells by qPCR
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Safety & Tolerability of MRT5005 Administered by Nebulization in Adults With Cystic Fibrosis
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • Drug: MRT5005
    Nebulization of MRT5005
  • Drug: Normal saline
    Normal Saline for Inhalation
Study Arms  ICMJE
  • Experimental: Low Dose
    8 mg MRT5005
    Intervention: Drug: MRT5005
  • Experimental: Low/Mid Dose
    12 mg MRT5005
    Intervention: Drug: MRT5005
  • Experimental: Mid Dose
    16 mg MRT5005
    Intervention: Drug: MRT5005
  • Experimental: Mid/High Dose
    20 mg MRT5005
    Intervention: Drug: MRT5005
  • Experimental: High Dose
    24 mg MRT5005
    Intervention: Drug: MRT5005
  • Placebo Comparator: Placebo Comparator
    Normal Saline 0.9% USP
    Intervention: Drug: Normal saline
  • Experimental: Daily Dose
    20 mg MRT5005 delivered in 5 consecutive daily doses of 4mg
    Intervention: Drug: MRT5005
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. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 28, 2020)
40
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2017)
32
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Elizabeth Brown 781-386-7261 ebrown@translate.bio
Contact: Caroline O'Hara 8572092450 cohara@translate.bio
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03375047
Other Study ID Numbers  ICMJE MRT5005-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Translate Bio, Inc.
Study Sponsor  ICMJE Translate Bio, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Translate Bio, Inc.
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP