Clinical trial NCT04120883: Oral Hydroxychloroquine (HCQ) for Retinitis Pigmentosa Caused by P23H- Rhodopsin (RHO)
Official title: Oral Hydroxychloroquine for Retinitis Pigmentosa Caused by P23H-RHO (Substitution of Proline to Histidine at Codon 23 of the Rhodopsin Protein)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Retinitis Pigmentosa
Keywords: P23H-RHO
eye disease
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Cures Within Reach
First posted: 2019-10-09
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change in Ellipsoid zone area measured by Spectral-Domain Optical Coherence Tomography (SD-OCT)
timeFrame: screening up to 18 months
measure: Change in Retinal sensitivity (decibels) measured by scotopic and mesopic microperimetry
timeFrame: screening up to 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: David Zacks, MD
role: PRINCIPAL_INVESTIGATOR
References: