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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 : Recruiting
First Posted : August 29, 2017
Last Update Posted : October 9, 2018
Sponsor:
Collaborator:
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: LAU-7b Drug: Placebo oral capsule Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
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
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
Estimated Study Start Date : October 10, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: LAU-7b
Active drug fenretinide (as LAU-7b capsules)
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

Placebo Comparator: Placebo
Placebo oral capsule (as inactive capsules identical to active arm)
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.




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. The time to first protocol-defined pulmonary exacerbation [ Time Frame: From baseline to 28 weeks ]
    Reports of pulmonary exacerbation during the trial

  4. The incidence of protocol-defined pulmonary exacerbation [ Time Frame: From baseline to 28 weeks ]
    Reports of pulmonary exacerbation during the trial

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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


Other Outcome Measures:
  1. 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

  2. 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.

  3. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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) or Symdeko® (ivacaftor/tezacaftor), patients must be taking it for a minimum of 3 months prior to screening, and deemed to tolerate it;
  • No change in CF and allowed systemic chronic therapy for a minimum of 1 month 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 1 month 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03265288


Contacts
Contact: Jean-Marie Houle, PhD 514-941-2313 jmhoule@laurentpharma.com
Contact: Radu Pislariu, MD 514-513-2252 rpislariu@laurentpharma.com

  Show 25 Study Locations
Sponsors and Collaborators
Laurent Pharmaceuticals Inc.
Cystic Fibrosis Foundation Therapeutics
Investigators
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

Responsible Party: Laurent Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03265288     History of Changes
Other Study ID Numbers: LAU-14-01
First Posted: August 29, 2017    Key Record Dates
Last Update Posted: October 9, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Laurent Pharmaceuticals Inc.:
Inflammation
Essential Fatty Acids
Inflammation resolution
Docosahexaenoic acid
Lung function

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases