Clinical trial NCT03375047: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
CF
Lead sponsor: Translate Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2017-12-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Types, frequency and severity of treatment-emergent Adverse Events
timeFrame: 12 months after last dose
Secondary outcomes:
measure: Biological activity of nebulized MRT5005
timeFrame: 4 weeks after last dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: University of Indiana
state: Indiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
References:
citation: 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.