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

University of Michigan

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Retinitis Pigmentosa

Treatments: Drug: Hydroxychloroquine lower dose; Drug: Hydroxychloroquine higher dose

Study type: Interventional

Funder types: Other

Identifiers

NCT04120883

HUM00164470

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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8 participants in 2 patient groups

HCQ treatment 1

Experimental group

Description:

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.

Treatment:

Drug: Hydroxychloroquine lower dose

HCQ treatment 2

Experimental group

Description:

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.

Treatment:

Drug: Hydroxychloroquine higher dose