Hydroxychloroquine Administration for Reduction of Pexophagy

Brief Title

Hydroxychloroquine Administration for Reduction of Pexophagy

Official Title

Hydroxychloroquine Administration for Reduction of Pexophagy

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.

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 Phase

Phase 2

Study Type


Primary Outcome

Electroretinogram (ERG) voltage changes.

Secondary Outcome

 Eye examination: Optical Coherence Tomography


Zellweger Syndrome



Study Arms / Comparison Groups

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


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 11, 2019

Completion Date

May 5, 2020

Primary Completion Date

May 5, 2020

Eligibility Criteria

        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.




6 Months - 40 Years

Accepts Healthy Volunteers



Neal Sondheimer, MD, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

The Hospital for Sick Children

Study Sponsor

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

Verification Date

December 2020