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HARP: Hydroxychloroquine Administration for Reduction of Pexophagy

Sponsor
The Hospital for Sick Children (Other)
Overall Status
Completed
CT.gov ID
NCT03856866
Collaborator
(none)
3
Enrollment
1
Location
2
Arms
15.8
Actual Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A series of N-of-1, crossover, randomized, placebo-controlled, double-blinded trial. Hydroxychloroquine (HCQ) and a crossover to placebo (order is randomized and blinded) will be administered in liquid suspension for 84 days (12 weeks) each with an 84 day washout in between. We hypothesize that HCQ will reduce peroxisomal turnover, which will arrest ongoing injury in PBDs caused by PEX1, PEX6 or PEX26.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
3 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
A randomized, blinded, placebo controlled, crossover N of 1 trial.A randomized, blinded, placebo controlled, crossover N of 1 trial.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
All parties will be masked except for research pharmacy who will do the randomization.
Primary Purpose:
Treatment
Official Title:
Hydroxychloroquine Administration for Reduction of Pexophagy
Actual Study Start Date :
Jan 11, 2019
Actual Primary Completion Date :
May 5, 2020
Actual Study Completion Date :
May 5, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Hydroxychloroquine

Hydroxychloroquine: liquid suspension, 4mg/kg/day by mouth, divided bid for 84 days.

Drug: Hydroxychloroquine
Hydroxychloroquine: 4mg/kg/day, divided bid.
Other Names:
  • Apo-Hydroxyquine
  • Plaquenil

    		•
    Placebo Comparator: Placebo

    Liquid suspension compounded to mimic the taste, appearance and texture of the investigational agent.

    Drug: Placebo
    Liquid suspension compounded to mimic the active hydroxycholoquine interventional agent.

    Outcome Measures

    Primary Outcome Measures

    1. Electroretinogram (ERG) voltage changes. [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.

    2. Change in the red blood cell levels of plasmalogen. [12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.]

      Change in the red blood cell levels of plasmalogen (18:0 dimethylacetals/18:0 ratio).

    3. Change in the plasma levels of phytanic acid. [12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.]

      Change in the plasma levels of phytanic acid.

    4. Change in the plasma levels of very-long chain fatty acids. [12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.]

      Change in the plasma levels of very-long chain fatty acids (C26/C22).

    Secondary Outcome Measures

    1. Eye examination: Optical Coherence Tomography [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.

    2. Eye examination: Visual Acuity [12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.]

      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.

    3. Pediatric Inventory for Parents (PIP) following the treatment arms. [36 week. Measurements following each treatment arm.]

      The PIP is a validated measure of parental stress related to the care for children with chronic illness.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Months to 40 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Hospital for Sick Children Toronto Ontario Canada M5G1X8

    Sponsors and Collaborators

    • The Hospital for Sick Children

    Investigators

    • Principal Investigator: Neal Sondheimer, MD, The Hospital for Sick Children

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Neal Sondheimer, Staff Physician - Clinical and Metabolic Genetics, The Hospital for Sick Children
    ClinicalTrials.gov Identifier:
    NCT03856866
    Other Study ID Numbers:
    • 1000061385
    First Posted:
    Feb 27, 2019
    Last Update Posted:
    Dec 17, 2020
    Last Verified:
    Dec 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    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.:
    Yes
    Keywords provided by Neal Sondheimer, Staff Physician - Clinical and Metabolic Genetics, The Hospital for Sick Children
    PBD, Zellweger spectrum, PBD-ZSD
    Additional relevant MeSH terms:
    Zellweger Syndrome
    Hydroxychloroquine

    Study Results

    No Results Posted as of Dec 17, 2020