Principal Investigator: Paul Bernstein
Keywords: Inherited retinal disease , Gene therapy , Clinical research trial Department: Ophthalmology-Services
IRB Number: 00132411
Specialty: Ophthalmology
Sub Specialties: Retinal Diseases
Recruitment Status: Active, not recruiting

Contact Information

Susan Allman
Kimberley.Wegner@hsc.utah.edu
801-581-5142

Simple Summary

To evaluate the safety and tolerability of gene therapy with 4D-125 for the treatment of X-linked retinitis pigmentosa caused by mutations in the RPGR gene

Inclusion Criteria

Inclusion Criteria for Natural History Cohort

  1. Male, ≥ 6 years of age at the time of informed consent

  2. Hemizygous non-syndromic RPGR mutation confirmed by genetic testing from a CLIA-certified laboratory during pre-screening if not previously documented

  3. Clinical diagnosis of non-syndromic retinitis pigmentosa

  4. At least one eye with the following, as assessed by the Investigator:

    1. BCVA ≥ 34 ETDRS letters (~20/200)

    2. measurable ellipsoid zone (EZ) area > 0.5mm2 line on macular SD-OCT, confirmed by a central reading center

    3. mean total retinal sensitivity 1 db on microperimetry confirmed by a central reading center

  5. Ability to perform tests of visual and retinal function and structure, and ability to comply with other protocol-specified procedures as assessed by Investigator

  6. Provide written informed consent.  Minors must provide written or verbal assent (if possible) and informed consent by a legally authorized representative (i.e. parent/guardian)

Inclusion Criteria for Interventional Cohorts

  1. Male, > 18 years of age

  2. Hemizygous non-syndromic RPGR mutation confirmed by genetic testing from a CLIA-certified laboratory during pre-screening if not previously documented

  3. Clinical diagnosis of non-syndromic retinitis pigmentosa

  4. Ability to perform tests of visual and retinal function and structure, and ability to comply with other protocol-specified procedures

  5. Phase I Dose Exploration:  At least one eye amenable to IVT injection, AND:

    1. BCVA < 78 ETDRS letters (~20/32) and > 34 ETDRS letters (~20/200)

    2. measurable ellipsoid zone line on macular SD-OCT, as confirmed by a central reading center

    3. > 5 non-zero points on microperimetry and mean total retinal sensitivity assessed by microperimetry > 0.1 db and < 8 db confirmed by central reading center

  6. Phase 2 Dose Expansion:  At least one eye amenable to IVT injection AND both eyes must have:

    1. BCVA > 34 ETDRS letters (~20/200)

    2. measurable ellipsoid zone line on macular SD-OCT, as confirmed by a central reading center

    3. and mean total retinal sensitivity assessed by microperimetry > 1 db confirmed by central reading center

  7. To prevent possible transmission of investigational product via seminal fluid, all sexually active males must agree to use a condom during intercourse for 3 months after administration of investigational product; and should not father a child or donate sperm during this period.

  8. Provide written informed consent.

Exclusion Criteria

Exclusion Criteria (All Cohorts) 

  1. Received an investigational drug, agent, device, or therapy (ocular or non-ocular) in the 6 months prior to receiving 4D-125

  2. Prior gene therapy (ocular or non-ocular) and/or ocular stem cell therapy

  3. Pre-existing eye conditions or surgical complications that would preclude participation in an interventional clinical trial or interfere with the interpretation of study endpoints NOTE: The presence of macular edema due to XLRP is not considered exclusionary

  4. Cataract surgery, vitrectomy, retinal laser, intraocular (non-steroid) and/or peri-ocular injection in the eye designated for injection within 6 months prior to receiving 4D-125 (interventional cohorts only)

  5. History of intraocular inflammation or intraocular steroid use in either eye

  6. Contraindication to oral prednisone, or use of topical corticosteroids; or presence of condition that may preclude the use of corticosteroids or immunosuppressive agents 

  7. Intercurrent illness or condition that, in the opinion of the Investigator, may place the subject at an unacceptable risk, prevent the subject from completing the trial, or confound interpretation of trial results

Participant Reimbursement

Participants will be paid $48 per visit for out of pocket expenses incurred to attend the required clinic visits up to a total of $432 for completion of study. Additional assistance with travel expenses is available with prior approval.