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

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

Tracking Information

• First Submitted Date: September 7, 2017
• First Posted Date: December 15, 2017
• Last Update Posted Date: November 16, 2020
• Actual Study Start Date: May 10, 2018
• Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 28, 2020)

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 (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

Current Secondary Outcome Measures (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 (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: Study to Evaluate the Safety & Tolerability of MRT5005 Administered by Nebulization in Adults With Cystic Fibrosis
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cystic Fibrosis

Intervention

• Drug: MRT5005
  Nebulization of MRT5005
• Drug: Normal saline
  Normal Saline for Inhalation

Study Arms

• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: January 28, 2020): 40
• Original Estimated Enrollment (submitted: December 11, 2017): 32
• Estimated Study Completion Date: December 2021
• Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03375047
• Other Study ID Numbers: 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

• Plan to Share IPD: Undecided

• Current Responsible Party: Translate Bio, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Translate Bio, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Translate Bio, Inc.
• Verification Date: November 2020