Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

CNTF Implants for CNGB3 Achromatopsia (CNTF-CNGB3-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01648452
Recruitment Status : Completed
First Posted : July 24, 2012
Results First Posted : February 25, 2014
Last Update Posted : November 21, 2016
Sponsor:
Information provided by (Responsible Party):
Paul A. Sieving, M.D., National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE July 20, 2012
First Posted Date  ICMJE July 24, 2012
Results First Submitted Date  ICMJE January 9, 2014
Results First Posted Date  ICMJE February 25, 2014
Last Update Posted Date November 21, 2016
Study Start Date  ICMJE July 2012
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 30, 2016)
  • 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 Measures  ICMJE
 (submitted: July 20, 2012)
The primary outcome is the number and severity of adverse event and systemic and ocular toxicities at six months post-implantation.
Change History Complete list of historical versions of study NCT01648452 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2016)
  • 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 tested by the Nagel anomaloscope, American Optical Hardy Rand Rittler (AOHRR) color plates, and a low vision version of the Cambridge Color Test (LvCCT) implemented on a ViSaGe System (Cambridge Research Systems Ltd., Rochester, UK) using custom-written software. Hardy Rand Rittler testing followed the guidelines accompanying the test and administered under a Macbeth Lamp at 300 lux.
  • Number of Participants Who Experienced an Improvement in Color Discrimination and/or Matching 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 ]
    Color hue discrimination was tested by the Nagel anomaloscope, American Optical Hardy Rand Rittler (AOHRR) color plates, and a low vision version of the Cambridge Color Test (LvCCT) implemented on a ViSaGe System (Cambridge Research Systems Ltd., Rochester, UK) using custom-written software. Hardy Rand Rittler testing followed the guidelines accompanying the test and administered under a Macbeth Lamp at 300 lux.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2012)
  • 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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CNTF Implants for CNGB3 Achromatopsia
Official Title  ICMJE 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.
  • Have 20/100 vision or worse in at least one eye.
  • Are not pregnant or nursing.

Design:

  • To determine if you can take part, we will ask about your medical history and do a physical examination and an eye examination. Blood and urine samples will be taken.
  • This study requires 11 visits to the National Eye Institute over 3 years.
  • One visit will be for the implant surgery. The implant will be placed in one eye only.
  • Study visits will take place 1 day after implant surgery, and again 1 week later and 1 month, 3 months, 6 months, 1 year, 1.5 years and 3 years later. These visits will help us evaluate the safety and benefit of the implant on your eye.
  • At the 3 year visit, you can choose to keep the CNTF implant in your eye, or you can have us remove it.
Detailed Description

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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Eye Disease
  • Achromatopsia
Intervention  ICMJE Biological: NT-501 CNTF-releasing implant
20 ng/day released into the eye
Study Arms  ICMJE Experimental: NT-501 CNTF-releasing implant
Ocular implantation of a NT-501 CNTF-releasing capsule (20 ng/day) in one eye (the study eye) at baseline
Intervention: Biological: NT-501 CNTF-releasing implant
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 20, 2012)
5
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

To be eligible, the following inclusion criteria must be met, where applicable.

  • Participant must be 18 years of age or older.
  • Participant must carry two alleles for CNGB3 gene mutations and no cyclic nucleotide-gated channel alpha 3 (CNGA3) sequence variations as confirmed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
  • Participant must understand and sign the protocol informed consent.
  • Both female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse, or must agree to use contraception during the first six months following implantation. Acceptable forms of contraception include:hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods (diaphragm, condom) with spermicide, or surgical sterilization (tubal ligation).

Exclusion Criteria:

A participant is not eligible if any of the following exclusion criteria are present.

  • Participant has a history of other ocular disease likely to contribute significantly to visual loss (e.g., optic neuropathy, glaucoma, uveitis, or other retinal disease).
  • Participant is judged by the investigator as not sufficiently healthy to safely undergo ophthalmic surgery.
  • Participant is on anticoagulant therapy that cannot be safely stopped peri-operatively at the implant procedure. Patients on warfarin will always be excluded. Patients on aspirin will be asked to stop the medication at least seven days prior to the surgery (when not contraindicated by the underlying medical condition). The stoppage period for other anticoagulant medications is based on the best clinical judgment of the investigator surgeon and is variable depending on the patient's medical condition and the type of medication.
  • Participant has had diagnosis or treatment of a malignancy (excluding non-melanoma skin cancer) within the previous five years.
  • Participant has received investigational treatment in another clinical study related to an ocular condition in the last six months.
  • Participant is pregnant, lactating or planning to become pregnant in the first six months following implantation.

Study Eye Eligibility Criteria:

The participant must have at least one eye meeting all inclusion criteria and none of the exclusion criteria listed below.

Study Eye Inclusion Criteria:

The study eye must have a best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity letterscore of ≤ 53 (i.e., ≤ 20/100). The visual acuity from the first baseline visit (Baseline 1) will be used for eligibility determination in case of a change in visual acuity at the second baseline visit (Baseline 2).

Study Eye Exclusion Criteria:

  • The study eye has a choroidal nevus or ocular neoplasm with potential risk for malignant transformation.
  • The study eye is judged by the investigator, based on history or examination findings, as high-risk for retinal detachment, vitreous hemorrhage, infection, or uveitis.
  • The study eye has lens, cornea, or other media opacities precluding adequate visualization and testing of the retina.
  • The study eye has undergone intraocular surgery within 12 months prior to enrollment.

Study Eye Selection Criteria in Cases of Bilateral Disease:

  • As this is a genetic condition that usually affects both eyes to a similar degree, if both eyes of a participant meet the study eye eligibility criteria and have comparable visual acuity, the study eye will be selected at the investigator's medical judgment after consultation with the participant.
  • In case of an eye with lower visual acuity, that eye will be selected as the study eye.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01648452
Other Study ID Numbers  ICMJE 120167
12-EI-0167
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Paul A. Sieving, M.D., National Institutes of Health Clinical Center (CC)
Study Sponsor  ICMJE National Eye Institute (NEI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Paul A Sieving, MD, PhD National Eye Institute (NEI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP