Oral Hydroxychloroquine (HCQ) for Retinitis Pigmentosa Caused by P23H- Rhodopsin (RHO)

Oral Hydroxychloroquine for Retinitis Pigmentosa Caused by P23H-RHO (Substitution of Proline to Histidine at Codon 23 of the Rhodopsin Protein)

This research study is being done to learn what effect 12 months of treatment with oral hydroxychloroquine (HCQ) will have on the retina in people with retinitis pigmentosa (RP). The hypothesis is that treatment with HCQ is safe and tolerable in patients with autosomal dominant retinitis pigmentosa (adRP) caused by P23H-RHO, and may arrest progression of retinal degeneration by altering the autophagy pathway in photoreceptors.

Participants that meet eligibility and agree to the study will be asked to take the study medication (HCQ) for 12 months and have evaluations for up to approximately 18 months from the baseline visit. There will be a total of 6 visits (1 is a phone visit) and will include general examinations, blood work, electrocardiograms, along with special testing of the retina.

Study Overview

• Status: Recruiting
• Conditions: Retinitis Pigmentosa
• Intervention / Treatment: Drug: Hydroxychloroquine lower dose; Drug: Hydroxychloroquine higher dose

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Callie Gordon; Phone Number: 734-615-8560; Email: callieg@umich.edu
• Study Contact Backup: Name: Courtney Snyder; Phone Number: 734-936-9798; Email: cosoto@umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Callie Gordon; Phone Number: 734-615-8560; Email: callieg@umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Stated willingness to comply with all study procedures and availability for the duration of the study
• Signed and dated informed consent form
• Early Treatment Diabetic Retinopathy Study Best Corrected Visual Acuity (ETDRS BCVA) of 20 letters (approximately 20/400 Snellen) or better in at least one eye
• Clinical diagnosis of autosomal dominant retinitis pigmentosa
• Confirmed to have one copy of the P23H-RHO pathogenic variant by genetic testing at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory
• Clarity of ocular media and adequate pupillary dilation to allow for adequate clinical ocular examination and retinal imaging
• Ability to perform testing required by the study as determined by the investigator
• Ability to take oral medication (medication tablets must be swallowed whole) and be willing to adhere to the daily medication regimen
• For females of reproductive potential: use of highly effective contraception beginning no later than 1 week after the first screening visit, and agreement to use such a method during study participation and through the end of the washout period (6 months after the end of HCQ administration)
• Agreement to adhere to Lifestyle Considerations throughout study duration (take the study drug with meals, avoid taking over-the-counter antacids or kaolin-containing products 4 hours before or after taking the study drug)

Exclusion Criteria:

• Use of any other drugs which are known to prolong the QT interval
• Concurrent use of any of the following drugs, if the drug cannot be discontinued or substituted: digoxin, antiepileptic medications, cimetidine, methotrexate, cyclosporine, praziquantel, ampicillin
• Current or previous use of tamoxifen
• Pregnancy or lactation
• Known allergy or hypersensitivity to hydroxychloroquine or any other 4-aminoquinoline drugs (chloroquine, amodiaquine, mefloquine, quinacrine, etc.), or known history of glucose-6-phosphate dehydrogenase deficiency
• Treatment with another investigational medical intervention for retinitis pigmentosa within 3 months, or any ever previous treatment with an investigational surgical intervention
• Any pre-existing cardiac, renal, hepatic, or hematologic disease, any prior history of psoriasis or porphyria, or any alcoholism
• Abnormal screening laboratory values including aspartate transaminase (AST) or alanine transaminase (ALT) > 2.0 x upper limit of normal, subnormal glomerular filtration rate (< 90 mL/min/1.73m2) or abnormal complete blood count attributable to underlying hematologic disease such as malignancy, aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HCQ treatment 1; In treatment arm 1, the dose of study drug will be 4 mg/kg/day. The daily dose will not exceed 400 mg. In both groups, the dose will be rounded down to 100, 200, 300, or 400 mg/day.	Drug: Hydroxychloroquine lower dose; The participants weight will be measured and converted to kilograms. The participants will receive 4 mg/kg/day. At the first follow-up visit (4 months) weight will be re-measured and the study drug dosing will be adjusted accordingly if the dosing has changed. Participants receiving 100 mg daily will be instructed to ingest one 200 mg tablet every other day. Participants receiving 200 mg daily will be instructed to ingest one 200 mg tablet daily. Participants receiving 300 mg daily will be instructed to alternate days ingesting two 200 mg tablets and one 200 mg tablet. Participants receiving 400 mg daily will be instructed to ingest two 200 mg tablets daily.; Other Names: plaquenil
Experimental: HCQ treatment 2; In treatment arm 2, the dose of the study drug will be 5 mg/kg/day. The daily dose will not exceed 400 mg. In both groups, the dose will be rounded down to 100, 200, 300, or 400 mg/day.	Drug: Hydroxychloroquine higher dose; The start of intervention for treatment arm 2 of the study will be delayed until preliminary safety of the drug is established with the 6 patients in treatment arm 1 at the first follow-up visit (4 months). The participants in this group will receive 5 mg/kg/day. At the first follow-up visit (4 months) weight will be re-measured and the study drug dosing will be adjusted accordingly if the dosing has changed. Participants receiving 100 mg daily will be instructed to ingest one 200 mg tablet every other day. Participants receiving 200 mg daily will be instructed to ingest one 200 mg tablet daily. Participants receiving 300 mg daily will be instructed to alternate days ingesting two 200 mg tablets and one 200 mg tablet. Participants receiving 400 mg daily will be instructed to ingest two 200 mg tablets daily.; Other Names: plaquenil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ellipsoid zone area measured by Spectral-Domain Optical Coherence Tomography (SD-OCT)	These will be performed at: screening, baseline, 4 months, 12 months, and 18 months	screening up to 18 months
Change in Retinal sensitivity (decibels) measured by scotopic and mesopic microperimetry	These will be performed at: screening, baseline, 4 months, 12 months, and 18 months	screening up to 18 months

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Cures Within Reach
• Investigators: Principal Investigator: David Zacks, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2020
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: October 8, 2019
• First Submitted That Met QC Criteria: October 8, 2019
• First Posted (Actual): October 9, 2019

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: eye disease; P23H-RHO
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Dystrophies; Retinitis; Retinitis Pigmentosa; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: HUM00164470

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified, individual participant data that underlie reported results will be shared.
• IPD Sharing Time Frame: Data be available beginning 9 months after publication and ending 36 months after publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal can access the data. Types of analyses: to achieve proposed aims. Proposals should be directed to the study Principal Investigator. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No