Clinical Trial: CNTF Implants for CNGB3 Achromatopsia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Study of the NT-501 Intraocular Implant Releasing Ciliary Neurotrophic Factor (CNTF) in Participants With CNGB3 Achromatopsia

Brief Summary:

Background:

  • Achromatopsia is an inherited condition that causes vision loss because cells in the retina do not work properly. It causes loss of acuity, sensitivity to light, and loss of color vision. There are no effective treatments for achromatopsia.
  • Four genes currently are known to cause achromatopsia. One of these, the cyclic nucleotide-gated channel beta 3 (CNGB3) gene, is the cause in about 50 percent of people.
  • CNTF is a natural chemical found in the body that promotes survival and function of nerve cells. CNTF has been shown to be effective in treating retinal disease in animals and can slow vision loss.
  • CNTF has also been studied in over 250 people with retinal disease other than achromatopsia. In these studies, a CNTF implant was placed into the eye during a simple surgery. The implant releases CNTF inside the eye, near the retina. These studies suggested that a CNTF implant might help vision in some eye diseases.

Objectives:

  • To learn whether a CNTF implant is safe for people with CNGB3 achromatopsia.
  • To learn whether CNTF can improve visual acuity or color vision, and whether it may reduce sensitivity to light in people with CNGB3 achromatopsia.

Eligibility:

You may be able to take part in this study if you:

  • Are at least 18 years old.
  • Test positive for mutations in the CNGB3 gene and have no mutations in another achromatopsia gene.

    Detailed Summary:

    Objective: The objective of this study is to evaluate the safety of ocular NT-501 device with encapsulated NT-201 cells releasing Ciliary Neurotrophic Factor (CNTF) to the retina of participants affected with CNGB3 achromatopsia.

    Study Population: Five participants affected with CNGB3 achromatopsia will be enrolled, with one eye treated per participant.

    Design: This is a Phase I/II, prospective, single-center study. One eye of each participant will receive a vitreous NT-501 device implant releasing CNTF. The study will be completed once the final participant has received three years of follow-up.

    Outcome Measures: The primary outcome is the number and severity of adverse events and systemic and ocular toxicities at six months post-implantation. Additional safety of ocular CNTF implants in participants with CNGB3 achromatopsia will be determined from assessment of retinal function, ocular structure and occurrence of adverse events at all time points. Secondary outcomes include changes in visual function including visual acuity and color vision, electroretinogram (ERG) responses, and retinal imaging with optical coherence tomography (OCT).


    Sponsor: National Eye Institute (NEI)

    Current Primary Outcome:

    • Number of Adverse Events at Six Months Post-Implantation [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation ]
      The primary outcome is the total number of adverse events reported within six months post-implantation.
    • Number of Severe Adverse Events at Six Months Post-Implantation [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation ]
      The number of severe adverse events reported within six months post-implantation.
    • Number of Ocular Adverse Events at Six Months Post-Implantation [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation ]
      The number of eye-related adverse events reported within six months post-implantation.
    • Number of Non-Ocular Adverse Events at Six Months Post-Implantation [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation ]
      The number of non eye-related adverse events reported within six months post-implantation.


    Original Primary Outcome: The primary outcome is the number and severity of adverse event and systemic and ocular toxicities at six months post-implantation.

    Current Secondary Outcome:

    • Number of Adverse Events at All Time Points Post-Implantation [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation ]
      The total number of adverse events reported from Day 1 post-implantation through study completion at Year 3.
    • Number of Severe Adverse Events at All Time Points Post-Implantation [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation ]

      The total number of severe adverse events reported from Day 1 post-implantation through study completion at Year 3.

      Although there were two serious adverse events (SAEs) reported during the study, only one event's severity was classified as "severe."

    • Number of Ocular Adverse Events at All Time Points Post-Implantation [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation ]
      The total number of eye-related adverse events reported from Day 1 post-implantation through study completion at Year 3.
    • Number of Non-Ocular Adverse Events at All Time Points Post-Implantation [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation ]
      The total number of non eye-related adverse events reported from Day 1 post-implantation through study completion at Year 3.
    • Number of Participants Who Experienced an Improvement in Visual Acuity of Greater Than 0.3 logMAR (Logarithm of the Minimum Angle of Resolution) Post-Implantation in the Study Eye. [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation ]

      Improvement of visual acuity was assessed on both the study and control eyes. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. .

      The LogMAR scale [expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30)] converts the geometric sequence of a traditional chart to a linear scale. It measures VA loss; positive values indicate vision loss, whereas negative values denote normal or better VA. A lower LogMAR value indicates better VA. For example, a visual acuity of 20/20 corresponds to a logMAR value of zero (0), and a visual acuity of 20/100 corresponds to a LogMAR value of 0.7.

    • Number of Participants Who Experienced an Improvement in Visual Acuity of Greater Than 0.3 logMAR (Logarithm of the Minimum Angle of Resolution) Post-Implantation in the Untreated Control Eye. [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation ]

      Improvement of visual acuity was assessed on both the study and control eyes. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. .

      The LogMAR scale [expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30)] converts the geometric sequence of a traditional chart to a linear scale. It measures VA loss; positive values indicate vision loss, whereas negative values denote normal or better VA. A lower LogMAR value indicates better VA. For example, a visual acuity of 20/20 corresponds to a logMAR value of zero (0), and a visual acuity of 20/100 corresponds to a LogMAR value of 0.7.

    • Number of Participants Who Experienced an Increase in Either the Rod or Cone Electroretinogram (ERG) Responses of More Than 75% Post-Implantation in the Study Eye. [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation ]
      Full-field ERGs were recorded according to International Society of Clinical Electrophysiology of Vision Standards (ISCEV).
    • Number of Participants Who Experienced an Increase in Either the Rod or Cone Electroretinogram (ERG) Responses of More Than 75% Post-Implantation in the Untreated Control Eye. [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation ]
      Full-field ERGs were recorded according to International Society of Clinical Electrophysiology of Vision Standards (ISCEV).
    • Number of Participants Who Experienced an Improvement in Color Discrimination and/or Matching Post-Implantation in the Study Eye. [ Time Frame: Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation ]
      Color hue discrimination was tes

      Original Secondary Outcome:

      • Additional safety of ocular CNTF implants in participants with CNGB3 achromatopsia will be determined from assessment of retinal function, ocular structure and occurrence of adverse events at all time points.
      • Secondary Outcomes Include Changes in Visual Function Including Visual Acuity and Color Vision, Electroretinogram (ERG) Response, and Retinal Imaging With Optical Coherence Tomography (OCT).


      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: July 20, 2012
      Date Started: July 2012
      Date Completion:
      Last Updated: September 30, 2016
      Last Verified: September 2016