An International Phase II, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of LAU-7b administered once-daily for 6 months for the treatment of CF.
An International Phase II, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of LAU-7b administered once-daily for 6 months for the treatment of CF. All patients will remain on their CF standard-of-care treatments over the trial duration. The goal for the treatment with LAU-7b in CF is to preserve lung function by reducing the persistent inflammation in the lung and to improve its capacity to defend against resistant bacteria such as Pseudomonas aeruginosa. The treatment regimen will consist of 6 consecutive "dosing cycles" of 21 days each, spaced by study drug-free periods of 7 days. A total of 136 eligible adult patients with CF will be randomized to receive 300 mg LAU-7b or placebo in a 1:1 ratio. The participation in the study will last about 7 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
166
LAU-7b will be administered orally once-a-day with the first meal of the day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
Placebo will be administered orally once-a-day with the first meal of the day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)
Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph. The outcome measure is presented using the Least Squares Mean at the Week 24 time point and the Least Squares Mean of all post-baseline time points through Week 24 averaged.
Time frame: From baseline to 24 weeks
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
This was assessed through adverse event monitoring at all visits, including spontaneously reported events and those obtained through serial probing of the subjects, and from safety laboratory tests
Time frame: From Baseline to 28 weeks
The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids
Assessed through 4 blood sampling occasions during the trial. Plasma samples were analyzed using a validated LC/MS method and corrected for phospholipid content. Highest proportion of normalization during treatment was determined versus analyte ranges obtained from a group of 20 healthy, non-CF individuals.
Time frame: From baseline to 28 weeks
The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial
Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph.
Time frame: From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial
The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial
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Long Beach Memorial Medical Center
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
UC Davis Medical Center, Division of Pulmonary & Critical Care Medicine
Sacramento, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Division of pulmonary, critical care and sleep medicine, University of Florida
Gainesville, Florida, United States
Memorial Healthcare System, Joe DiMaggio Children's Hospital Cystic Fibrosis & Pulmonary Center
Hollywood, Florida, United States
Avanza Medical Research Center
Pensacola, Florida, United States
St-Luke's CF Center of Idaho
Boise, Idaho, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
...and 30 more locations
Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph.
Time frame: From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial
The Time to First Protocol-Defined Pulmonary Exacerbation
Reports of IV antibiotics-treated pulmonary exacerbations during the trial that meet the Fuch's criteria and after the first treatment cycle.
Time frame: From baseline to 28 weeks
The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial
The number per subject of Protocol-Defined IV antibiotics-treated pulmonary exacerbations (events) during the trial that meet the Fuch's criteria. Also presented are the number per subject of IV antibiotics-treated pulmonary exacerbations and combined number per subject of IV- or Oral antibiotics-treated pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
Time frame: From baseline to 28 weeks
The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
The time to first change and usage of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
Time frame: From baseline to 28 weeks
Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
Usage (number of antibiotic treatments per subject) of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
Time frame: From baseline to 28 weeks
Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
Usage (days) of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
Time frame: From baseline to 28 weeks
The Change From Baseline of Systemic Markers of Inflammation in Blood
This was assessed through scheduled blood sampling during the trial on three occasions. Both ITT and PP populations results presented. Samples were analyzed using validated analytical methods.
Time frame: Change from baseline to Week 24
The Change From Screening of the Body Weight
This was assessed through serial weighing during the trial. Measurements performed at clinical sites using calibrated balances.
Time frame: From screening to 28 weeks
The Change From Screening of the Body Mass Index (BMI)
This was assessed through serial weighing during the trial and calculation of BMI. Measurements performed at clinical sites using calibrated balances.
Time frame: From screening to 28 weeks
The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum
This was assessed through induced sputum (and spontaneously obtained during COVID-19 pandemic) on 3 occasions during the trial. Samples were analyzed at a central laboratory. An area under the curve (AUC from baseline to Week 24 inclusive) of colony forming unit/mL is calculated.
Time frame: From screening to Week 24
The Impact (From Baseline) on Overall Health, Daily Life, Perceived Well-being and Symptoms Measured With the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
This was assessed through administration of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at four planned times during the trial. The CFQ-R respiratory sub-score (range 0-100) was extracted and analyzed. The Minimum Clinically Important Difference (MCID) for the respiratory sub-score is 4 units. A higher score means a better outcome.
Time frame: From baseline to 24 weeks
The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood
This was assessed through serial blood sampling during the trial. Samples were analyzed using validated methods at specialized laboratories.
Time frame: From baseline to 24 weeks