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

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

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

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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


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




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



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04120883


Contacts
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Contact: Callie Gordon 734-615-8560 callieg@umich.edu
Contact: Yu Cheng MD Zhao, MD 734-232-8262

Locations
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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
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Principal Investigator: David Zacks, MD University of Michigan
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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    Key Record Dates
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.

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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:
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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