Cystic Fibrosis
Conditions
Brief summary
Mucus clearance is impaired in cystic fibrosis. Inhaled surfactants may reduce adhesive forces between mucus and airway surfaces and improve mucus clearance. This in turn my improve lung health. The investigators propose to measure mucus clearance before and after lucinactant or vehicle administration in patients with cystic fibrosis.
Detailed description
This single-center pilot study is designed as a double-blind, randomized, cross-over clinical trial to evaluate the effects of inhaled lucinactant, an investigational peptide-containing synthetic surfactant (6 ml of 20 mg total phospholipid (TPL)/mL solution x 5 doses) in patients with mild to moderate CF lung disease. Lucinactant and vehicle will be delivered via a 510k approved vibrating mesh nebulizer, the Pari eFlowTM. The study duration corresponds to a 2-10 day screening phase, followed by a 20 day post-randomization phase that consists of two treatment periods (3 days each) and a washout period (14 days). A total of 16 patients will be enrolled and randomly assigned to one of two treatment sequences (Lucinactant followed by vehicle or vehicle followed by lucinactant). The primary outcome will be the rate of MC, as assessed via gamma scintigraphy, post-lucinactant and post vehicle. Secondary outcomes will include the rate of cough clearance (CC), lung clearance index (LCI), absolute change from baseline in FEV1 after 5 doses of study medication, CF-specific quality of life score (via CFQ-R instrument), in vitro assessments of sputum rheology, and various safety parameters.
Interventions
DRUGLucinactant first
lucinactant 120 mg (20 mg/ml) x 5 doses over 24 hours, then washout period x 14 days, then vehicle x 5 doses over 24 hrs
DRUGPlacebo first
6 mL normal saline x 5 doses over 24 hours, then washout period x 14 days, then lucinactant x 5 doses over 24 hours
Sponsors
Cystic Fibrosis Foundation
Windtree Therapeutics
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cystic fibrosis * FEV1\>40%
Exclusion criteria
* Unstable lung disease * Unable or unwilling to stop hypertonic saline and dornase alfa for 3 days prior to each study period * Relevant drug allergy or intolerance * Recent investigational drug use (30 days)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mucociliary Clearance | 1 hour after final treatment (5th dose) minus baseline | Clearance of radiolabeled particles, following inhalation, are followed over time. Average clearance rate through 60 minutes post inhaled isotope deposition is calculated. Absolute difference between baseline and post-treatment (e.g. \<60 minutes after the last dose of lucinactant or placebo) reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spirometry | after 5 doses | Percent change (relative) in FEV1 between pre-treatment baseline and following 5 doses of study treatment. Post treatment values obtained 3 and approximately 22 hours after 5th dose were averaged to determine the treatment effect. |
Countries
United States
Participant flow
Pre-assignment details
two week washout period between treatment phases of this cross-over study
Participants by arm
| Arm | Count |
|---|---|
| Lucinactant First, Then Placebo 20 mg/ml x 6 ml (5 doses) lucinactant then 0.9% NaCl x 6 ml (5 doses) | 8 |
| Placebo First, Then Lucinactant 0.9% NaCl x 6 ml (5 doses) then 20 mg/ml x 6 ml lucinactant (5 doses) | 8 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Lucinactant First, Then Placebo | Placebo First, Then Lucinactant | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 7 Participants | 15 Participants |
| Age, Continuous | 28.3 years STANDARD_DEVIATION 8.8 | 25.9 years STANDARD_DEVIATION 6.4 | 27.1 years STANDARD_DEVIATION 7.5 |
| Baseline Mucociliary Clearance Rate | 9.2 Percentage Clearance STANDARD_DEVIATION 4.8 | 12.0 Percentage Clearance STANDARD_DEVIATION 10.5 | 10.5 Percentage Clearance STANDARD_DEVIATION 8.1 |
| Region of Enrollment United States | 8 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 16 | 8 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 |
Outcome results
Primary
Change in Mucociliary Clearance
Clearance of radiolabeled particles, following inhalation, are followed over time. Average clearance rate through 60 minutes post inhaled isotope deposition is calculated. Absolute difference between baseline and post-treatment (e.g. \<60 minutes after the last dose of lucinactant or placebo) reported.
Time frame: 1 hour after final treatment (5th dose) minus baseline
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lucinactant | Change in Mucociliary Clearance | 7.4 percent clearance | Standard Deviation 9.3 |
| Placebo | Change in Mucociliary Clearance | 9.5 percent clearance | Standard Deviation 10 |
Secondary
Spirometry
Percent change (relative) in FEV1 between pre-treatment baseline and following 5 doses of study treatment. Post treatment values obtained 3 and approximately 22 hours after 5th dose were averaged to determine the treatment effect.
Time frame: after 5 doses
Population: per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lucinactant | Spirometry | .81 percent change | Standard Deviation 0.9 |
| Placebo | Spirometry | .23 percent change | Standard Deviation 1.1 |