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

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ClinicalTrials.gov Identifier: NCT03265288
Recruitment Status : Completed
First Posted : August 29, 2017
Last Update Posted : October 5, 2021
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Laurent Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE February 21, 2017
First Posted Date  ICMJE August 29, 2017
Last Update Posted Date October 5, 2021
Actual Study Start Date  ICMJE October 10, 2018
Actual Primary Completion Date September 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 25, 2017)
  • Absolute change in percent predicted forced expiratory volume in 1 second (FEV1%) [ Time Frame: From baseline to 24 weeks ]
    Standardized, serial FEV1 measurements will be performed during the trial
  • The safety and tolerability of LAU-7b will be assessed by the incidence of treatment emergent adverse events compared to placebo [ Time Frame: From Baseline to 28 weeks ]
    This will be assessed through serial assessments and ad-hoc assessments
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2017)
  • The proportion of patients achieving normalization of the arachidonic acid, docosahexaenoic acid and their ratio in phospholipids [ Time Frame: From baseline to 28 weeks ]
    This will be assessed through serial blood sampling during the trial
  • The absolute and relative (%) change in FEV1 percent predicted at 3, 7, 11, 15 and 28 weeks into the trial [ Time Frame: From baseline to 3, 7, 11, 15 and 28 weeks into the trial ]
    Standardized, serial FEV1 measurements will be performed during the trial
  • The time to first protocol-defined pulmonary exacerbation [ Time Frame: From baseline to 28 weeks ]
    Reports of pulmonary exacerbation during the trial
  • The incidence of protocol-defined pulmonary exacerbation [ Time Frame: From baseline to 28 weeks ]
    Reports of pulmonary exacerbation during the trial
  • The time to first change and usage of antibiotic (other than chronic inhaled antibiotics already started prior to trial or oral chronic azithromycin) [ Time Frame: From baseline to 28 weeks ]
    Reports of pulmonary exacerbation and their treatment during the trial
  • The change from baseline of systemic markers of inflammation in blood [ Time Frame: From baseline to 28 weeks ]
    This will be assessed through serial blood sampling during the trial
  • The change from screening of the body weight and calculated Body Mass Index (BMI) [ Time Frame: From screening to 28 weeks ]
    This will be assessed through serial weighing during the trial
  • The overall change from screening of the Pseudomonas aeruginosa density (colony forming units) in the sputum [ Time Frame: From screening to Weeks 11 and 24 ]
    This will be assessed through induced sputum on 3 occasions during the trial
  • The impact (from baseline) on overall health, daily life, perceived well-being and symptoms measured with the Cystic Fibrosis Questionnaire-Revised (CFQ-R) [ Time Frame: From baseline to 28 weeks ]
    This will be assessed through administration of the questionnaire at planned times during the trial
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 25, 2017)
  • The change in metabolipidomic profile and in markers of oxidative stress in blood [ Time Frame: From baseline to 28 weeks ]
    This will be assessed through serial blood sampling during the trial
  • The change in metabolipidomic profile in blood, the systemic markers of inflammation in blood, the FEV1, the body weight and calculated BMI [ Time Frame: From baseline to 28 weeks ]
    Only in patients who experience a pulmonary exacerbation requiring intravenous antibiotics, this will be assessed prior to- and after the intravenous antibiotic course.
  • The change from baseline of systemic bone formation and resorption biomarkers [ Time Frame: Baseline and 24 weeks ]
    This will be assessed through blood sampling on 2 occasions during the trial
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double-blind, randomized, parallel groups and placebo-controlled trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Patients will be randomly assigned to take either the active drug (fenretinide capsule) or a matching inactive placebo (inactive capsule).
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • 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.
    Other Name: fenretinide
  • Drug: 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.
Study Arms  ICMJE
  • Experimental: LAU-7b
    Active drug fenretinide (as LAU-7b capsules)
    Intervention: Drug: LAU-7b
  • Placebo Comparator: Placebo
    Placebo oral capsule (as inactive capsules identical to active arm)
    Intervention: Drug: Placebo oral capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 12, 2021)
166
Original Estimated Enrollment  ICMJE
 (submitted: August 25, 2017)
136
Actual Study Completion Date  ICMJE September 15, 2021
Actual Primary Completion Date September 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03265288
Other Study ID Numbers  ICMJE LAU-14-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Laurent Pharmaceuticals Inc.
Study Sponsor  ICMJE Laurent Pharmaceuticals Inc.
Collaborators  ICMJE Cystic Fibrosis Foundation
Investigators  ICMJE
Study Chair: Larry C Lands, MD PhD McGill Uinversity Health Centre
Study Chair: Michael W Konstan, MD Rainbow Babies and Children's Hospital/ University Hospitals Cleveland Medical Center
PRS Account Laurent Pharmaceuticals Inc.
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP