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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: MRT5005
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, CF