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

• ClinicalTrials.gov Identifier: NCT04120883
• Recruitment Status: Recruiting
• First Posted: October 9, 2019
• Last Update Posted: February 28, 2020
• Sponsor: University of Michigan
• Collaborator: Cures Within Reach
• Information provided by (Responsible Party): David Zacks, University of Michigan

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Retinitis Pigmentosa	Drug: Hydroxychloroquine lower dose; Drug: Hydroxychloroquine higher dose	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: 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).
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Oral Hydroxychloroquine for Retinitis Pigmentosa Caused by P23H-RHO (Substitution of Proline to Histidine at Codon 23 of the Rhodopsin Protein)
• Actual Study Start Date: February 25, 2020
• Estimated Primary Completion Date: October 2022
• Estimated Study Completion Date: October 2022

Arms and Interventions

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 Name: 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 Name: plaquenil

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Callie Gordon; 734-615-8560; callieg@umich.edu

Contact: Yu Cheng MD Zhao, MD; 734-232-8262

Locations

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Callie Gordon 734-615-8560 callieg@umich.edu

Sponsors and Collaborators

University of Michigan

Cures Within Reach

Investigators

• Principal Investigator: David Zacks, MD; University of Michigan

More Information

• Responsible Party: David Zacks, Professor of Ophthalmology and Visual Sciences, University of Michigan
• ClinicalTrials.gov Identifier: NCT04120883
• Other Study ID Numbers: HUM00164470
• First Posted: October 9, 2019
• Last Update Posted: February 28, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified, individual participant data that underlie reported results will be shared.
• Supporting Materials: Study Protocol
• Time Frame: Data be available beginning 9 months after publication and ending 36 months after publication.
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David Zacks, University of Michigan:

P23H-RHO; eye disease

Additional relevant MeSH terms:

Retinitis; Retinitis Pigmentosa; Retinal Diseases; Eye Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Degeneration; Genetic Diseases, Inborn; Hydroxychloroquine; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents