Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults

Cystic Fibrosis Clinical Trial

— APPLAUD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03265288
• Other study ID #: LAU-14-01
• Status: Completed
• Phase: Phase 2
• Start date: October 10, 2018
• Est. completion date: September 15, 2021

Study information

• Verified date: October 2021
• Source: Laurent Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: September 15, 2021
• Est. primary completion date: September 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• LAU-7b
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 oral capsule
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.

Locations

Country	Name	City	State
Australia	Mater Misericordiae Ltd	Brisbane	Queensland
Australia	Monash Lung and Sleep, Monash Health	Clayton	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Institute of Respiratory Health, Harry Perkins Institute	Nedlands	Western Australia
Australia	Respiratory Medicine, John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Department of Respiratory Medicine, Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Department of Respiratory and Sleep Medicine, Westmead Hospital	Westmead	New South Wales
Canada	Centre d'études cliniques CIUSS SLJ, Hôpital Chicoutimi	Chicoutimi	Quebec
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec
Canada	McGill University Health Center	Montréal	Quebec
Canada	The Ottawa Hospital Center for Practice-Changing Research	Ottawa	Ontario
Canada	Centre de recherche de l'institut Universitaire de Cardiologie et de Pneumologie de Québec	Québec City	Quebec
Canada	Pacific Lung Research Institute at St. Paul's Hospital	Vancouver	British Columbia
United States	Albany Medical College	Albany	New York
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	St-Luke's CF Center of Idaho	Boise	Idaho
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University Hospitals Cleveland Medical Center, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Wayne State University, Harper University Hospital	Detroit	Michigan
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	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Medical College of Wisconsin, Div of Pulmonary and Critical Care Medicine	Milwaukee	Wisconsin
United States	The Minnesota Cystic Fibrosis Center, University of Minnesota	Minneapolis	Minnesota
United States	Morristown Medical Center, NJ Adult Cystic Fibrosis Center	Morristown	New Jersey
United States	Rutgers University Clinical Research Center, RW Johnson University Hospital	New Brunswick	New Jersey
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Avanza Medical Research Center	Pensacola	Florida
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Cystic Fibrosis Center, Doernbecher Children's Hospital, Oregon Health & Science University	Portland	Oregon
United States	Maine Medical Center Cystic Fibrosis Research	Portland	Maine
United States	Virginia Commonwealth University	Richmond	Virginia
United States	UC Davis Medical Center, Division of Pulmonary & Critical Care Medicine	Sacramento	California
United States	Washington University Medical School	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Laurent Pharmaceuticals Inc.	Cystic Fibrosis Foundation

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The change in metabolipidomic profile and in markers of oxidative stress in blood	This will be assessed through serial blood sampling during the trial	From baseline to 28 weeks
Other	The change in metabolipidomic profile in blood, the systemic markers of inflammation in blood, the FEV1, the body weight and calculated BMI	Only in patients who experience a pulmonary exacerbation requiring intravenous antibiotics, this will be assessed prior to- and after the intravenous antibiotic course.	From baseline to 28 weeks
Other	The change from baseline of systemic bone formation and resorption biomarkers	This will be assessed through blood sampling on 2 occasions during the trial	Baseline and 24 weeks
Primary	Absolute change in percent predicted forced expiratory volume in 1 second (FEV1%)	Standardized, serial FEV1 measurements will be performed during the trial	From baseline to 24 weeks
Primary	The safety and tolerability of LAU-7b will be assessed by the incidence of treatment emergent adverse events compared to placebo	This will be assessed through serial assessments and ad-hoc assessments	From Baseline to 28 weeks
Secondary	The proportion of patients achieving normalization of the arachidonic acid, docosahexaenoic acid and their ratio in phospholipids	This will be assessed through serial blood sampling during the trial	From baseline to 28 weeks
Secondary	The absolute and relative (%) change in FEV1 percent predicted at 3, 7, 11, 15 and 28 weeks into the trial	Standardized, serial FEV1 measurements will be performed during the trial	From baseline to 3, 7, 11, 15 and 28 weeks into the trial
Secondary	The time to first protocol-defined pulmonary exacerbation	Reports of pulmonary exacerbation during the trial	From baseline to 28 weeks
Secondary	The incidence of protocol-defined pulmonary exacerbation	Reports of pulmonary exacerbation during the trial	From baseline to 28 weeks
Secondary	The time to first change and usage of antibiotic (other than chronic inhaled antibiotics already started prior to trial or oral chronic azithromycin)	Reports of pulmonary exacerbation and their treatment during the trial	From baseline to 28 weeks
Secondary	The change from baseline of systemic markers of inflammation in blood	This will be assessed through serial blood sampling during the trial	From baseline to 28 weeks
Secondary	The change from screening of the body weight and calculated Body Mass Index (BMI)	This will be assessed through serial weighing during the trial	From screening to 28 weeks
Secondary	The overall change from screening of the Pseudomonas aeruginosa density (colony forming units) in the sputum	This will be assessed through induced sputum on 3 occasions during the trial	From screening to Weeks 11 and 24
Secondary	The impact (from baseline) on overall health, daily life, perceived well-being and symptoms measured with the Cystic Fibrosis Questionnaire-Revised (CFQ-R)	This will be assessed through administration of the questionnaire at planned times during the trial	From baseline to 28 weeks