Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults
- Registration Number
- NCT03265288
- Lead Sponsor
- Laurent Pharmaceuticals Inc.
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 166
- Screening FEV1 between 40% and 100% predicted value for age, gender and height, in patients capable of properly performing the test;
- History of pulmonary exacerbation, defined as at least one (1) pulmonary exacerbation in the year prior to Screening which resulted in documented intravenous or Oral antibiotics;
- Patients are eligible independently of their history of pulmonary Pseudomonas aeruginosa (PsA) infection and their PsA status at screening;
- If taking Kalydeco® (ivacaftor), Orkambi® (ivacaftor/lumacaftor), Symdeko® (ivacaftor/tezacaftor) or other commercially available CFTR modulator products, patients must be taking it for a minimum of 3 months prior to screening if naïve to CFTR modulators and 1 month if switched from another CFTR modulator product and deemed to tolerate it;
- No change in CF and allowed systemic chronic therapy for a minimum of 5 weeks prior to randomization, of which 2 weeks minimum are prior to screening;
- Female patients of child bearing potential should be on highly effective contraceptive methods during the study;
- Male patients with spouse or partner of child bearing potential, or pregnant, are eligible if they use an appropriate method of contraception.
- Pregnancy: due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible;
- Breast milk feeding by study patient is NOT allowed;
- Clinically abnormal renal function: serum creatinine > 132 μM (1.5 mg/dL);
- Clinically abnormal liver function: Total bilirubin >1.5 x ULN (in the absence of demonstrated Gilbert's syndrome), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2.5 x ULN;
- Patients with plasma retinol levels below 0.7 µM;
- Presence of nyctalopia or hemeralopia at enrolment, or any other serious retinal, ophthalmological condition;
- Presence of serious dermatological conditions at entry, including inflammatory or xerotic skin pathologies such as psoriasis or ichthyosis;
- Intake of chronic systemic steroids in the month prior to screening and during the study;
- History of acute infections (viral/bacterial/fungal) within 5 weeks prior to randomization, of which 2 weeks minimum are prior to screening, whether or not treated and resolved;
- Presence of infection with Burkholderia cepacia (including all species within the Burkholderia cepacia complex group, and Burkholderia gladioli) in the 12 months prior to screening;
- Patients with a confirmed diagnosis (as per the Cystic Fibrosis Foundation diagnostic criteria) of Allergic BronchoPulmonary Aspergillosis (ABPA) and actively being treated with corticosteroids and/or anti fungal agents.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LAU-7b LAU-7b Active drug fenretinide (as LAU-7b capsules) Placebo Placebo oral capsule Placebo oral capsule (as inactive capsules identical to active arm)
- Primary Outcome Measures
Name Time Method Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) From baseline to 24 weeks 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.
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence From Baseline to 28 weeks 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
- Secondary Outcome Measures
Name Time Method The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids From baseline to 28 weeks 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.
The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial From baseline to 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.
The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial From baseline to 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.
The Time to First Protocol-Defined Pulmonary Exacerbation From baseline to 28 weeks Reports of IV antibiotics-treated pulmonary exacerbations during the trial that meet the Fuch's criteria and after the first treatment cycle.
The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial From baseline to 28 weeks 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.
The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) From baseline to 28 weeks 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.
Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) From baseline to 28 weeks 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.
Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) From baseline to 28 weeks Usage (days) of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
The Change From Baseline of Systemic Markers of Inflammation in Blood Change from baseline to Week 24 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.
The Change From Screening of the Body Weight From screening to 28 weeks This was assessed through serial weighing during the trial. Measurements performed at clinical sites using calibrated balances.
The Change From Screening of the Body Mass Index (BMI) From screening to 28 weeks This was assessed through serial weighing during the trial and calculation of BMI. Measurements performed at clinical sites using calibrated balances.
The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum From screening to Week 24 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.
The Impact (From Baseline) on Overall Health, Daily Life, Perceived Well-being and Symptoms Measured With the Cystic Fibrosis Questionnaire-Revised (CFQ-R) From baseline to 24 weeks 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.
The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood From baseline to 24 weeks This was assessed through serial blood sampling during the trial. Samples were analyzed using validated methods at specialized laboratories.
Trial Locations
- Locations (40)
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, 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
Scroll for more (30 remaining)Long Beach Memorial Medical Center🇺🇸Long Beach, California, United States