Clinical trial NCT03265288: Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults
Official title: APPLAUD: A Double-Blind, Randomized, Placebo-Controlled, Phase II Study of the Efficacy and Safety of LAU-7b in the Treatment of Cystic Fibrosis in Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Inflammation
Essential Fatty Acids
Inflammation resolution
Docosahexaenoic acid
Lung function
Lead sponsor: Laurent Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2017-08-29
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, parallel groups and placebo-controlled trial.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)
timeFrame: From baseline to 24 weeks
measure: Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
timeFrame: From Baseline to 28 weeks
Secondary outcomes:
measure: The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids
timeFrame: From baseline to 28 weeks
measure: The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial
timeFrame: From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial
measure: The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial
timeFrame: From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial
measure: The Time to First Protocol-Defined Pulmonary Exacerbation
timeFrame: From baseline to 28 weeks
measure: The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial
timeFrame: From baseline to 28 weeks
measure: The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
timeFrame: From baseline to 28 weeks
measure: Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
timeFrame: From baseline to 28 weeks
measure: Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
timeFrame: From baseline to 28 weeks
measure: The Change From Baseline of Systemic Markers of Inflammation in Blood
timeFrame: Change from baseline to Week 24
measure: The Change From Screening of the Body Weight
timeFrame: From screening to 28 weeks
measure: The Change From Screening of the Body Mass Index (BMI)
timeFrame: From screening to 28 weeks
measure: The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum
timeFrame: From screening to Week 24
measure: The Impact (From Baseline) on Overall Health, Daily Life, Perceived Well-being and Symptoms Measured With the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
timeFrame: From baseline to 24 weeks
measure: The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood
timeFrame: From baseline to 24 weeks
Other outcomes:
measure: The Change in Metabolipidomic Profile in Blood, the Systemic Markers of Inflammation in Blood, the FEV1, the Body Weight and Calculated BMI
timeFrame: From baseline to 28 weeks
measure: The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers
timeFrame: Baseline and 24 weeks
measure: The Change From Baseline of Bone Mineral Density
timeFrame: Baseline and 28 weeks
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center, Division of Pulmonary & Critical Care Medicine
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: Division of pulmonary, critical care and sleep medicine, University of Florida
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System, Joe DiMaggio Children's Hospital Cystic Fibrosis & Pulmonary Center
state: Florida
city: Pensacola
country: United States
facility: Avanza Medical Research Center
state: Florida
city: Boise
country: United States
facility: St-Luke's CF Center of Idaho
state: Idaho
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Portland
country: United States
facility: Maine Medical Center Cystic Fibrosis Research
state: Maine
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Wayne State University, Harper University Hospital
state: Michigan
city: Minneapolis
country: United States
facility: The Minnesota Cystic Fibrosis Center, University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Medical School
state: Missouri
city: Morristown
country: United States
facility: Morristown Medical Center, NJ Adult Cystic Fibrosis Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers University Clinical Research Center, RW Johnson University Hospital
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Cystic Fibrosis Center, Doernbecher Children's Hospital, Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Div of Pulmonary and Critical Care Medicine
state: Wisconsin
city: New Lambton Heights
country: Australia
facility: Respiratory Medicine, John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Department of Respiratory Medicine, Royal Prince Alfred Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Department of Respiratory and Sleep Medicine, Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Misericordiae Ltd
state: Queensland
city: Clayton
country: Australia
facility: Monash Lung and Sleep, Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Institute of Respiratory Health, Harry Perkins Institute
state: Western Australia
city: Vancouver
country: Canada
facility: Pacific Lung Research Institute at St. Paul's Hospital
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Center for Practice-Changing Research
state: Ontario
city: Chicoutimi
country: Canada
facility: Centre d'études cliniques CIUSS SLJ, Hôpital Chicoutimi
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Québec City
country: Canada
facility: Centre de recherche de l'institut Universitaire de Cardiologie et de Pneumologie de Québec
state: Quebec
Study officials:
affiliation: McGill Uinversity Health Centre
name: Larry C Lands, MD PhD
role: STUDY_CHAIR
affiliation: Rainbow Babies and Children's Hospital/ University Hospitals Cleveland Medical Center
name: Michael W Konstan, MD
role: STUDY_CHAIR
References: