Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, CF
Brief summary
This Phase 1/2, first-in-human study evaluated the safety and tolerability of single and multiple escalating doses of MRT5005 administered by nebulization to the respiratory tract of adult subjects with cystic fibrosis (CF).
Interventions
DRUGMRT5005
Nebulization of MRT5005
DRUGNormal saline
Normal Saline for Inhalation
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of CF as defined by both of the following: * Two CF disease-causing cystic fibrosis transmembrane conductance regulator (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. * Forced expiratory volume in 1 second (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, or 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. * Participants were receiving treatment with ivacaftor monotherapy (KALYDECO). * Parts A and B only: Were receiving treatment with triple combination therapy (TRIKAFTA). * Participants 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 was not an exclusion for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts A, B and D: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events | From the first dose of study treatment administration (Day 1) up to 48 weeks (end of the follow-up period) after the last dose of study treatment administration (Part A: Day 337, Part B: Day 365 and Part D: Day 341) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily had a causal relationship with the study treatment. A serious adverse event (SAE) was any untoward medical occurrence (whether considered to be related to study treatment or not) that at any dose: resulted in death; or was life-threatening; or required inpatient hospitalization or prolongation of existing hospitalization; or resulted in persistent or significant disability/incapacity; or was a congenital abnormality/birth defect; or was an important medical event. The TEAEs were defined as events that were newly reported or reported to worsen in severity after the start of study treatment up to 48 weeks (end of follow-up period) after the last dose of study treatment administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts A, B and D: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | Part A:BL, D1(8hPD), D2(24hPD), D3, D8, D15 and D29; Part B:BL, D1(6hPD), D2, D8(PrD and 6hPD), D9, D15(PrD and 6hPD), D16, D22(PrD and 6hPD), D23, D29(PrD and 6hPD), D30, D36, D43 and D57; Part D:BL, D1(2hPD), PrD on D2, D3, D4 and D5, D11, D18 and D32 | Spirometry was performed according to the guidelines published by the American Thoracic Society for standardization of spirometry. The ppFEV1 was assessed during the spirometry testing. For Parts A and B, the baseline value was defined as the average of the results from testing on Day -1 and at pre-dose on Day 1. For Part D, the baseline value was defined as the result from testing pre-dose on Day 1. Here, Baseline= BL, Day= D, pre-dose= PrD, hours post dose= hPD. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 16 active centers. A total of 53 participants were screened from 10 May 2018 to 22 February 2021, of which 11 were screen failures. Screen failures were mainly due to not meeting the eligibility criteria.
Pre-assignment details
Study consisted of 4 parts: Part A-single ascending dose (SAD), Part B-multiple ascending dose (MAD), Part C (bronchoscopy groups) and Part D (daily dosing). A total of 42 participants were randomized (3:1 ratio) in Parts A, B and D to receive either MRT5005 or placebo. Part C was removed from protocol in 3rd amendment (dated 29 July 2019) prior to any participant enrollment in Part C. Participants were allowed to take part in 1 part of study only and results of Parts A, B and D were reported.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized White | 2 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 5 | 0 / 6 | 0 / 2 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 5 / 5 | 6 / 6 | 2 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 1 / 3 | 1 / 3 | 3 / 4 | 1 / 3 | 1 / 3 | 0 / 4 | 2 / 3 | 2 / 5 | 1 / 6 | 1 / 2 |
Outcome results
None listed