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

NCT03265288 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: LAU-14-01
• Study Type: interventional
• Target: 166
• Locations: 3 countries
• Sites: 40

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.

Conditions

Cystic Fibrosis

Keywords

Inflammation; Essential Fatty Acids; Inflammation resolution; Docosahexaenoic acid; Lung function

Outcome Measures

Primary Outcomes (2)

• Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)

  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.

  From baseline to 24 weeks

• Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence

  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

  From Baseline to 28 weeks

Secondary Outcomes (14)

• The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids

  From baseline to 28 weeks

• 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

• 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

• The Time to First Protocol-Defined Pulmonary Exacerbation

  From baseline to 28 weeks

• The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial

  From baseline to 28 weeks

Other Outcomes (3)

• The Change in Metabolipidomic Profile in Blood, the Systemic Markers of Inflammation in Blood, the FEV1, the Body Weight and Calculated BMI

  From baseline to 28 weeks

• The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers

  Baseline and 24 weeks

• The Change From Baseline of Bone Mineral Density

  Baseline and 28 weeks

Study Arms (2)

LAU-7b

EXPERIMENTAL

Active drug fenretinide (as LAU-7b capsules)

Drug: LAU-7b

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo oral capsule

Interventions

LAU-7b DRUG

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.

Also known as: fenretinide

LAU-7b

Placebo oral capsule DRUG

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.

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laurent Pharmaceuticals Inc.: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (40)

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90227, United States

Location

UC Davis Medical Center, Division of Pulmonary & Critical Care Medicine

Sacramento, California, 95817, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Division of pulmonary, critical care and sleep medicine, University of Florida

Gainesville, Florida, 32610, United States

Location

Memorial Healthcare System, Joe DiMaggio Children's Hospital Cystic Fibrosis & Pulmonary Center

Hollywood, Florida, 33021, United States

Location

Avanza Medical Research Center

Pensacola, Florida, 32603, United States

Location

St-Luke's CF Center of Idaho

Boise, Idaho, 83712, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66103, United States

Location

Maine Medical Center Cystic Fibrosis Research

Portland, Maine, 04102, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University, Harper University Hospital

Detroit, Michigan, 48201, United States

Location

The Minnesota Cystic Fibrosis Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

Morristown Medical Center, NJ Adult Cystic Fibrosis Center

Morristown, New Jersey, 07962, United States

Location

Rutgers University Clinical Research Center, RW Johnson University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

University Hospitals Cleveland Medical Center, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Cystic Fibrosis Center, Doernbecher Children's Hospital, Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Medical College of Wisconsin, Div of Pulmonary and Critical Care Medicine

Milwaukee, Wisconsin, 53226, United States

Location

Respiratory Medicine, John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

Department of Respiratory Medicine, Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

Department of Respiratory and Sleep Medicine, Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Mater Misericordiae Ltd

Brisbane, Queensland, 4101, Australia

Location

Monash Lung and Sleep, Monash Health

Clayton, Victoria, 3168, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Institute of Respiratory Health, Harry Perkins Institute

Nedlands, Western Australia, 6009, Australia

Location

Pacific Lung Research Institute at St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

The Ottawa Hospital Center for Practice-Changing Research

Ottawa, Ontario, K1H 8L6, Canada

Location

Centre d'études cliniques CIUSS SLJ, Hôpital Chicoutimi

Chicoutimi, Quebec, G7H 5H6, Canada

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2X2P1, Canada

Location

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

Location

Centre de recherche de l'institut Universitaire de Cardiologie et de Pneumologie de Québec

Québec, Quebec, G1V 4G5, Canada

Location

MeSH Terms

Conditions

Cystic Fibrosis; Inflammation

Interventions

Fenretinide

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Limitations and Caveats

The APPLAUD study started enrollment in November 2018 and was conducted through the COVID-19 pandemic and during market introduction of ETI (elexacaftor/tezacaftor/ivacaftor) in the participating countries. However, the study protocol and the statistical plan were amended to address the higher dropout rates caused by these two factors during the clinical trial and to allow enrolment of patients stabilized on ETI as their background CFTR modulator therapy.

Results Point of Contact

• Title: Dr Jean-Marie Houle, VP Clinical Development
• Organization: Laurent Pharmaceuticals Inc.

jmhoule@laurentpharma.com

514-941-2313

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be randomly assigned to take either the active drug (fenretinide capsule) or a matching inactive placebo (inactive capsule).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized, parallel groups and placebo-controlled trial.

Study Record Dates

• First Submitted: February 21, 2017
• First Posted: August 29, 2017
• Study Start: November 5, 2018
• Primary Completion: September 15, 2021
• Study Completion: September 15, 2021
• Last Updated: October 9, 2024
• Results First Posted: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6); US (27); AU (7)