Safety Study of Fenretinide in Adult Patients With Cystic Fibrosis

NCT02141958 | Completed Phase 1 DMC

• 1 other identifier: MGU-4HPR-13-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and tolerability of ascending doses of a novel oral formulation of Fenretinide to adult cystic fibrosis (CF) patients, once-daily for 21 days (treatment cycle). This study will include up to three (3) dose levels with minimum 7 day breaks in between treatment cycles. For each dose level, blood samples will be collected for exploratory pharmacokinetic (PK) and pharmacodynamic (PD) evaluation.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Assessment of the safety and tolerability of ascending doses of oral Fenretinide, each dose to be administered to adult cystic fibrosis (CF) patients once-daily (QD) during a 21 days treatment cycle.

  Changes in clinical signs and symptoms of safety data during a 21 days treatment cycle, such safety data assessment including physical examinations, ECGs, vital signs, pulmonary function (spirometry), clinical laboratory results, assessment of ophthalmological condition, and adverse events reported. The safety data will be used to authorize dose escalations. Up to three (3) doses of Fenretinide will be assessed in up to three (3) treatment cycles of 21 days.

  During a 21 days treatment cycle, from time taking first dose (Day 1) through last day of each treatment cycle (Day 21)

Secondary Outcomes (3)

• Pharmacokinetic profile of the drug, measuring Cmax, Tmax, T1/2, AUC (area under the curve) and Css (steady state concentration), for each dose level

  Day 1 and 21 of each treatment cycle

• Pharmacodynamic lipid markers: plasma Arachidonic Acid (AA) and Docosahexaenoic Acid (DHA)

  At baseline and Day 21 of each treatment cycle

• Pharmacodynamic inflammatory markers: Immunoglobulin G, Interleukin 1β, Interleukin 6, Interleukin 8, Interleukin 10, Macrophage inflammatory protein-1β, Tumor necrosis factors and Vascular endothelial growth factor

  At baseline and Day 21 of each treatment t cycle

Other Outcomes (2)

• Pre-specified exploratory parameter: pulmonary function using the Forced Expiratory Volume in 1 second test

  At baseline and Day 21 of each treatment cycle

• Pre-specified exploratory parameter: quality of life using the Cystic Fibrosis Quality of life Questionnaire Revised (CFQ-R)

  At baseline and Day 21 of each treatment cycle

Study Arms (2)

Fenretinide

EXPERIMENTAL

Fenretinide will be administrated orally once per day for 21 consecutive days, in up to three treatment cycles of ascending doses, with a minimum of 7-day drug-free period between cycles. Twelve (12) patients will be on Fenretinide.

Drug: Fenretinide

Placebo

PLACEBO COMPARATOR

Four (4) patients will be on Placebo.

Drug: Placebo

Interventions

Fenretinide DRUG

Fenretinide oral capsules of 100mg, each selected dose being administered once daily for 21 days (treatment cycle). Up to three total daily dose levels will be assessed in the study, as follows: 100mg of Fenretinide (one capsule) for the first treatment cycle, 200mg of Fenretinide (two capsules) in the second treatment cycle, and 300mg or 400mg of Fenretinide (3 or 4 capsules) will be selected for the third treatment cycle, based on safety and PK data collected.

Fenretinide

Placebo DRUG

A matching placebo will be used to keep the study double-blind.

Placebo

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent
• Males or females
• years and older
• Diagnosis: Patients must have a diagnosis of cystic fibrosis (positive sweat chloride test) or confirmation of two genetic mutations, one mutation on each of the two alleles of the Cystic fibrosis transmembrane conductance regulator (CFTR) gene causing Cystic Fibrosis
• Chronic cystic fibrosis lung disease with baseline Forced Exploratory Volume in one second equal or superior to 40% predicted value for age, gender and height
• Clinically stable patients will be enrolled in the study, i.e. stable at least one month after successful treatment of pulmonary exacerbation
• Chronic pulmonary Pseudomonas aeruginosa colonization and/or infection (sustained microbiological evidence from sputum for the past 6 months, prior to enrollment)
• Pancreatic function: Patient must take pancrelipase supplementation if diagnosed with pancreatic insufficiency as prescribed by a physician. Enzyme supplementation should not be modified during the trial
• Female patients should be on an effective contraceptive method during the study.

You may not qualify if:

• Pregnancy : due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible
• Breastfeeding by study patient is NOT allowed
• Clinically abnormal renal function: Serum Creatinine \> 132 micromoles/L
• Clinically abnormal liver function: Total bilirubin \>1.5 x Upper Limit of the Normal range (ULN), Alanine Aminotransferase (ALT) and/or Aspartate AminoTransferase (AST) \> 3 x ULN and Alkaline Phosphatase (ALP) \> 2 x ULN
• Known history of a severe allergy or sensitivity to retinoids
• Presence of a cancerous tumor, active or in remission, treated or not
• Presence of nyctalopia or hemeralopia at enrolment, or any other serious retinal, ophthalmological condition (eg: retinitis pigmentosa, choroidoretinitis and xerophthalmia), including glaucoma
• Presence of serious dermatological conditions at entry, including inflammatory or xerotic pathologies such as psoriasis or ichthyosis
• Prior therapy with Fenretinide. Other retinoids (eg: vitamin A supplements) are allowed, but their dosing regimen should remain constant throughout the study
• Participation in another drug clinical trial within 30 days prior to the enrollment
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
• Patients unable to comply with the study protocol and follow-up schedule for any psychological, familial, sociological or geographical reason.
• Patients with known allergies to excipients in the oral capsule formulation proposed to be used in the study

Sponsors & Collaborators

• Elias Matouk: lead

Study Sites (1)

Montreal Chest Institute

Montreal, Quebec, H2X 2P4, Canada

Location

MeSH Terms

Conditions

Cystic Fibrosis

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Elias Matouk, MD

  Montreal Chest Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 20, 2014
• Study Start: April 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: July 12, 2016

Record last verified: 2016-07

Locations

CA (1)