Zellweger SyndromePhase 2HARPNCT03856866
Hydroxychloroquine Administration for Reduction of Pexophagy
A Phase 2 study testing Hydroxychloroquine in people with Zellweger Syndrome and Peroxisome Biogenesis Disorders, run by The Hospital for Sick Children at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 40 years
- Conditions the study is for
- Zellweger Syndrome, Peroxisome Biogenesis Disorders
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteCanada
- Study dates
- 11 Jan 2019to 5 May 2020
- Phase
- Phase 2
- 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 6 months to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- Hydroxychloroquine, Placebo
- Keywords
- PBD, Zellweger spectrum, PBD-ZSD
- Medical subject headings
- Zellweger Syndrome, Peroxisome biogenesis disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Apo-Hydroxyquine, Plaquenil
Hydroxychloroquine: 4mg/kg/day, divided bid.
PlaceboDrug
Liquid suspension compounded to mimic the active hydroxycholoquine interventional agent.
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine | Experimental | Hydroxychloroquine: liquid suspension, 4mg/kg/day by mouth, divided bid for 84 days. Receives: Drug: Hydroxychloroquine |
| Placebo | Placebo comparator | Liquid suspension compounded to mimic the taste, appearance and texture of the investigational agent. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Electroretinogram (ERG) voltage changes.
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.
Measured: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
Change in the red blood cell levels of plasmalogen.
Change in the red blood cell levels of plasmalogen (18:0 dimethylacetals/18:0 ratio).
Measured: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
Change in the plasma levels of phytanic acid.
Change in the plasma levels of phytanic acid.
Measured: 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.
Change in the plasma levels of very-long chain fatty acids (C26/C22).
Measured: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
Secondary outcomes (3)
Eye examination: Optical Coherence Tomography
Optical coherence tomography is an imaging study of the retina. OCT is routinely performed in clinical management of patients with peroxisomal disease.
Measured: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
Eye examination: Visual Acuity
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.
Measured: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
Pediatric Inventory for Parents (PIP) following the treatment arms.
The PIP is a validated measure of parental stress related to the care for children with chronic illness.
Measured: 36 week. Measurements following each treatment arm.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2019
- Study start11 Jan 2019
- Primary completion5 May 2020
- Study completion5 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Zellweger SyndromeStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- A randomized, blinded, placebo controlled, crossover N of 1 trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Neal Sondheimer, The Hospital for Sick Children
- Investigators
- Neal Sondheimer, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03856866
- Sponsor's protocol ID
- 1000061385
- Acronym
- HARP
- Status last verified
- Dec 2020
- First submitted
- 5 Nov 2018
- Last updated
- 17 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxychloroquine Administration for Reduction of Pexophagy
- ClinicalTrials.gov ID
- NCT03856866
- Acronym / sponsor ID
- HARP / 1000061385
- Keywords
- PBD, Zellweger spectrum, PBD-ZSD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- 11 Jan 2019 (actual)
- Primary completion
- 5 May 2020 (actual)
- Study completion
- 5 May 2020 (actual)
- First posted
- 27 Feb 2019 (actual)
- 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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A randomized, blinded, placebo controlled, crossover N of 1 trial.
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine | Experimental | Drug: HydroxychloroquineHydroxychloroquine: liquid suspension, 4mg/kg/day by mouth, divided bid for 84 days. |
| Placebo | Placebo comparator | Drug: PlaceboLiquid suspension compounded to mimic the taste, appearance and texture of the investigational agent. |
Who may qualify
- Ages
- 6 months to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
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 |
|---|---|---|
| HydroxychloroquineAlso: Apo-Hydroxyquine, PlaquenilHydroxychloroquine: 4mg/kg/day, divided bid. | Drug | Hydroxychloroquine |
| PlaceboLiquid suspension compounded to mimic the active hydroxycholoquine interventional agent. | Drug | Placebo |
Primary outcome
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.
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.
Change in the red blood cell levels of plasmalogen (18:0 dimethylacetals/18:0 ratio).
Change in the plasma levels of phytanic acid.
Time frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
Change in the plasma levels of phytanic acid.
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.
Change in the plasma levels of very-long chain fatty acids (C26/C22).
3 secondary outcomes
Eye examination: Optical Coherence Tomography
Time frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
Eye examination: Visual Acuity
Time frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.
Pediatric Inventory for Parents (PIP) following the treatment arms.
Time frame: 36 week. Measurements following each treatment arm.
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 17 Dec 2020.
- Individual participant dataSharing planned: Undecided
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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.
Neal Sondheimer, MD principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxychloroquine in people with Zellweger Syndrome and Peroxisome Biogenesis Disorders, run by The Hospital for Sick Children 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 4 inclusion and 5 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 17 Dec 2020. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Electroretinogram (ERG) voltage changes. (time frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.). The study lists 4 primary outcomes in all. 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 17 Dec 2020; AzTrials last refreshed its copy on 5 Nov 2026.