Cystic FibrosisPhase 1NCT02141958
Safety Study of Fenretinide in Adult Patients With Cystic Fibrosis
A Phase 1 study testing Fenretinide in people with Cystic Fibrosis, run by Elias Matouk at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Fenretinide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2014to Feb 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent
- Males or females
- 18 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Adaptive Phase I Intra-patient Dose Escalation Study of Fenretinide in Adult Cystic Fibrosis Patients
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.
Read the detailed description
Patients with cystic fibrosis have an innate imbalance of essential fatty acids, with increased arachidonic acid (AA) levels, decreased docosahexanoic acid (DHA) levels, and elevated AA/DHA ratio. An increasing amount of evidence suggests that this lipid imbalance is a primary effect in CF, playing a major role in the infection-inflammation vicious cycle that leads to respiratory failure. Fenretinide, a derivative of vitamin A, was shown to correct the AA/DHA imbalance in lungs and blood plasma in specific animal model of CF, resulting in reduced lung inflammation and decrease in the severity of pulmonary infections with Pseudomonas aeruginosa.
This is a single center, randomized, double-blinded, placebo-controlled Phase 1 clinical study to evaluate the safety and tolerability of up to 3 increasing oral doses of Fenretinide compared to placebo, and to evaluate the pharmacokinetics of Fenretinide in adult CF patients chronically infected with Pseudomonas aeruginosa. A single cohort of 16 clinically stable adult patients will be randomized to either Fenretinide or placebo, in a 3:1 randomization scheme (12 active, 4 placebo).
- Conditions
- Cystic Fibrosis
- Being tested
- Fenretinide, Placebo
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FenretinideDrug
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.
PlaceboDrug
A matching placebo will be used to keep the study double-blind.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Fenretinide |
| Placebo | Placebo comparator | Four (4) patients will be on Placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Cmax, Tmax, T 1/2, and Css (steady state concentration) with target plasma levels of Fenretinide 1-2 µM as a pharmacokinetic / pharmacodynamic biological activity
Measured: Day 1 and 21 of each treatment cycle
Pharmacodynamic lipid markers: plasma Arachidonic Acid (AA) and Docosahexaenoic Acid (DHA)
Arachidonic Acid as omega-6 proinflammatory fatty acid and Docosahexaenoic Acid (DHA) as an omega-3 anti-inflammatory fatty acid.
Measured: 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
Measured: At baseline and Day 21 of each treatment t cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2014 (estimated)
- Study startApr 2014
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Elias Matouk
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Elias Matouk, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Elias Matouk, MD, Principal investigator, Montreal Chest Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02141958
- Sponsor's protocol ID
- MGU-4HPR-13-01
- Status last verified
- Jul 2016
- First submitted
- 13 May 2014
- Last updated
- 12 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Adaptive Phase I Intra-patient Dose Escalation Study of Fenretinide in Adult Cystic Fibrosis Patients
- ClinicalTrials.gov ID
- NCT02141958
- Acronym / sponsor ID
- MGU-4HPR-13-01
- Conditions
- Cystic Fibrosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Elias MatoukUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 20 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients with cystic fibrosis have an innate imbalance of essential fatty acids, with increased arachidonic acid (AA) levels, decreased docosahexanoic acid (DHA) levels, and elevated AA/DHA ratio. An increasing amount of evidence suggests that this lipid imbalance is a primary effect in CF, playing a major role in the infection-inflammation vicious cycle that leads to respiratory failure. Fenretinide, a derivative of vitamin A, was shown to correct the AA/DHA imbalance in lungs and blood plasma in specific animal model of CF, resulting in reduced lung inflammation and decrease in the severity of pulmonary infections with Pseudomonas aeruginosa.
This is a single center, randomized, double-blinded, placebo-controlled Phase 1 clinical study to evaluate the safety and tolerability of up to 3 increasing oral doses of Fenretinide compared to placebo, and to evaluate the pharmacokinetics of Fenretinide in adult CF patients chronically infected with Pseudomonas aeruginosa. A single cohort of 16 clinically stable adult patients will be randomized to either Fenretinide or placebo, in a 3:1 randomization scheme (12 active, 4 placebo).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fenretinide | Experimental | Drug: FenretinideFenretinide 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. |
| Placebo | Placebo comparator | Drug: PlaceboFour (4) patients will be on Placebo. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed Informed Consent
- Males or females
- 18 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FenretinideFenretinide 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. | Drug | Fenretinide |
| PlaceboA matching placebo will be used to keep the study double-blind. | Drug | Placebo |
Primary outcome
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.
Time frame: During a 21 days treatment cycle, from time taking first dose (Day 1) through last day of each treatment cycle (Day 21)
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.
3 secondary outcomes
Pharmacokinetic profile of the drug, measuring Cmax, Tmax, T1/2, AUC (area under the curve) and Css (steady state concentration), for each dose level
Time frame: Day 1 and 21 of each treatment cycle
Pharmacodynamic lipid markers: plasma Arachidonic Acid (AA) and Docosahexaenoic Acid (DHA)
Time frame: 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
Time frame: At baseline and Day 21 of each treatment t cycle
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elias Matouk, MD principal investigator
Montreal Chest Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fenretinide in people with Cystic Fibrosis, run by Elias Matouk at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: During a 21 days treatment cycle, from time taking first dose (Day 1) through last day of each treatment cycle (Day 21)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2016.