Hydroxychloroquine Administration for Reduction of Pexophagy

NCT03856866 | Completed Phase 2 FDA Drug

• 1 other identifier: 1000061385
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Zellweger Syndrome; Peroxisome Biogenesis Disorders

Keywords

PBD, Zellweger spectrum, PBD-ZSD

Outcome Measures

Primary Outcomes (4)

• 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.

  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).

  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.

  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).

  12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.

Secondary Outcomes (3)

• Eye examination: Optical Coherence Tomography

  12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.

• Eye examination: Visual Acuity

  12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm.

• Pediatric Inventory for Parents (PIP) following the treatment arms.

  36 week. Measurements following each treatment arm.

Study Arms (2)

Hydroxychloroquine

EXPERIMENTAL

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

Drug: Hydroxychloroquine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine: 4mg/kg/day, divided bid.

Also known as: Apo-Hydroxyquine, Plaquenil

Hydroxychloroquine

Placebo DRUG

Liquid suspension compounded to mimic the active hydroxycholoquine interventional agent.

Placebo

Eligibility Criteria

• Age: 6 Months - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Conditions

Zellweger Syndrome; Peroxisome biogenesis disorders

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Neal Sondheimer, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All parties will be masked except for research pharmacy who will do the randomization.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician - Clinical and Metabolic Genetics

Model Details: A randomized, blinded, placebo controlled, crossover N of 1 trial.

Study Record Dates

• First Submitted: November 5, 2018
• First Posted: February 27, 2019
• Study Start: January 11, 2019
• Primary Completion: May 5, 2020
• Study Completion: May 5, 2020
• Last Updated: December 17, 2020

Record last verified: 2020-12

Locations

CA (1)