- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03856866
Hydroxychloroquine Administration for Reduction of Pexophagy (HARP)
Study Overview
Status
Intervention / Treatment
Detailed Description
HARP is a phase II/III, double-blind, placebo-controlled, randomized, crossover series N-of-1 study of the effect of hydroxychloroquine (HCQ) in patients with peroxisomal biogenesis disorders (PBD-ZSD). Patients eligible for the study must have a laboratory diagnosis of PEX1, PEX6 or PEX26 dependent PBD-ZSD from a CLIA or SCC-certified clinical laboratory, a history of abnormal VLCFA levels, and must be at least 84 days from their last HCQ dose. Patients will be excluded for known sensitivity to HCQ, known glucose-6-phosphate dehydrogenase deficiency, if they have an expected survival of less than 9 months or if they are participating in another interventional clinical trial.
HCQ will be administered at a dose of 4mg/kg/day divided into two doses, as a liquid suspension that can be given orally or through nasogastric or gastric tube. Within the study, HCQ or placebo will be given for 84 days, followed by a washout period of 84 days followed by an 84 day crossover to the alternative therapy to assess the effect the study measures.
Study measures will be completed at four intervals (initiation, end of period 1, start of period 2, end of trial). Ophthalmological monitoring of patients has three components, electroretinogram (ERG), visual acuity testing and optical coherence tomography (OCT). Plasma levels of very long-chain fatty acids (VLCFA), plasmalogen and phytanic acid will be assessed. Parents will also be administered The Pediatric Inventory for Parents (PIP), a questionnaire that was developed to evaluate the stress associated with parenting a seriously ill child, at the end of period 1 and period 2.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
Ontario
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Toronto, Ontario, Canada, M5G1X8
- The Hospital for Sick Children
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosed with a peroxisomal defect due to PEX1, PEX6 or PEX26 through a SCC or CLIA-certified clinical genetic testing laboratory.
- Abnormal plasma very-long-chain fatty acid levels.
- All therapies available in Canada have been considered and ruled out, have failed or were justified as being unsuitable for the patient. We note that there are no therapies available.
- At least 84 days from last HCQ dose
Exclusion Criteria:
- Known sensitivity to HCQ.
- Known Glucose-6-phosphate dehydrogenase deficiency.
- Expected survival is less than six months.
- The patient does not provide informed consent.
- The patient is participating in another interventional clinical trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Hydroxychloroquine
Hydroxychloroquine: liquid suspension, 4mg/kg/day by mouth, divided bid for 84 days.
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Hydroxychloroquine: 4mg/kg/day, divided bid.
Other Names:
|
PLACEBO_COMPARATOR: Placebo
Liquid suspension compounded to mimic the taste, appearance and texture of the investigational agent.
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Liquid suspension compounded to mimic the active hydroxycholoquine interventional agent.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Electroretinogram (ERG) voltage changes.
Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
|
Electroretinograms are a diagnostic test that measures the electric activity within cells in response to stimulus.
ERG voltages are depressed in peroxisomal disease, and the quantitative evaluation of ERG voltage is another measure that has been used as an endpoint for clinical trials in peroxisomal disease.
Change in b-wave voltage before and after treatment period.
|
12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Change in the red blood cell levels of plasmalogen.
Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Change in the red blood cell levels of plasmalogen (18:0 dimethylacetals/18:0 ratio).
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12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Change in the plasma levels of phytanic acid.
Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Change in the plasma levels of phytanic acid.
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12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Change in the plasma levels of very-long chain fatty acids.
Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Change in the plasma levels of very-long chain fatty acids (C26/C22).
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12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Eye examination: Optical Coherence Tomography
Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
|
Optical coherence tomography is an imaging study of the retina.
OCT is routinely performed in clinical management of patients with peroxisomal disease.
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12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Eye examination: Visual Acuity
Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Visual acuity testing evaluates the visual performance of patients using the reading of a logMAR chart.
Visual acuity testing is routinely performed in clinical management of patients with peroxisomal disease.
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12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
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Pediatric Inventory for Parents (PIP) following the treatment arms.
Time Frame: 36 week. Measurements following each treatment arm.
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The PIP is a validated measure of parental stress related to the care for children with chronic illness.
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36 week. Measurements following each treatment arm.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Neal Sondheimer, MD, The Hospital for Sick Children
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Kidney Diseases
- Urologic Diseases
- Congenital Abnormalities
- Liver Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Abnormalities, Multiple
- Peroxisomal Disorders
- Zellweger Syndrome
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Hydroxychloroquine
Other Study ID Numbers
- 1000061385
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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