A Study to Determine the Safety and Efficacy of NT-501 in Macular Telangiectasia Type 2 - Protocol A

A Phase III Multicenter Randomized, Sham Controlled, Study to Determine the Safety and Efficacy of NT-501 in Macular Telangiectasia Type 2

This study is a phase 3, randomized, multi-center study to evaluate the efficacy and safety of the NT-501 implants in participants with macular telangiectasia type 2.

Study Overview

• Status: Completed
• Conditions: Macular Telangiectasia Type 2 (MacTel)
• Intervention / Treatment: Combination product: NT-501; Procedure: Sham Procedure

Detailed Description

Phase 3, prospective, multicenter, masked, sham-controlled study with the overall study objective to evaluate the efficacy and safety of NT-501 for the treatment of MacTel. Secondary objective was to evaluate the safety of NT-501 in participants with MacTel. This was a multicenter study conducted at 20 study centers in the United States, Australia, France, and the United Kingdom.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Lions Eye Institute
• France
  • Paris, France, 75010
    • Lariboisiere Hospital
• United Kingdom
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital NHS Foundation Trust
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust
• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic Medical Group
    • Los Angeles, California, United States, 90095
      • Jules Stein Eye Institute / David Geffen School of Medicine
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Stanford University
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Retina Consultants of Southern Colorado, P.C.
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Retina Associates of New Orleans
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institute of Health, NIH
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Associated Retinal Consultants, P.C.
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Retina Associates of Cleveland, Inc.
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74114
      • Tulsa Retina Consultants
  • Oregon
    • Portland, Oregon, United States, 97221
      • Retina Northwest, PC
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Southeastern Retina Associates, PC
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah John A. Moran Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Participant must have at least one study eye with a positive diagnosis of MacTel with evidence of fluorescein leakage typical of MacTel and at least one of the other features that include hyperpigmentation that is outside of a 500 micron radius from the center of the fovea, retinal opacification, crystalline deposits, right-angle vessels, or inner/outer lamellar cavities
2. Participant must have an Inner Segment - Outer Segment Junction Line (IS/OS) Photo Receptor (PR) break in the study eye(s) and en face EZ (area of IS/OS loss) as measured by spectral-domain optical coherence tomography (SD-OCT) between 0.16 mm^2 and 2.00 mm^2
3. Participant's best corrected visual acuity (BCVA) is a 54-letter score or better (20/80 or better) as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at screening.
4. Participant must have steady fixation in the foveal or parafoveal area and sufficiently clear media for good quality photographs
5. Participant must be greater than 21 years of age or less than 80 years of age at screening
6. Participant must be able to provide written informed consent to participate in the study, in accordance with the International Conference on Harmonisation Good Clinical Practices guidelines, and local regulations, before initiating any study-related procedures
7. Women of childbearing potential must agree to use highly effective contraception (Germany and France only)

Key Exclusion Criteria:

1. Participant is medically unable to comply with study procedures or follow-up visits
2. Participant received intravitreal steroid therapy for non-neovascular MacTel within the last 3 months
3. Participant has ever received intravitreal anti-vascular endothelial growth factor (VEGF) therapy in the study eye OR has, within the past 3 months, received intravitreal anti-VEGF in the fellow eye at randomization
4. Participant has evidence of ocular disease other than MacTel that, in the judgment of the examining physician, may confound the diagnosis, procedures or outcome of the study (eg, glaucoma, severe nonproliferative or proliferative diabetic retinopathy, uveitis)
5. Participant has a chronic requirement (eg, ≥ 4 weeks at a time) for ocular medications and/or has a diagnosed disease that, in the judgment of the examining physician, may be vision threatening or may affect the primary outcome (artificial tears are permitted)
6. Participant has evidence of intraretinal neovascularization or subretinal neovascularization (SRNV), as evidenced by hemorrhage, hard exudate, subretinal fluid or intraretinal fluid in either eye
7. Participant has evidence of central serous chorio-retinopathy in either eye
8. Participant has evidence of pathologic myopia in either eye
9. Participant has significant corneal or media opacities in either eye
10. Participant has had a vitrectomy, penetrating keratoplasty, trabeculectomy, or trabeculoplasty
11. Participant has any of the following lens opacities: cortical opacity > standard 3, posterior subcapsular opacity > standard 2, or a nuclear opacity > standard 3 as measured on the Age-Related Eye Disease Study (AREDS) clinical lens grading system
12. Participant has undergone lens removal in the previous 3 months or YAG laser within 4 weeks
13. Participant was a participant in any other clinical trial of an intervention (drug or device) within the last 6 months
14. Participant is on chemotherapy
15. Participant is pregnant or breastfeeding
16. Participant has a history of malignancy that would compromise the 24-month study survival
17. Participant with a history of ocular herpes virus in either eye
18. Participant has, in the opinion of the investigator, any physical or mental condition that would increase the risk of participation in the study or may interfere with the study procedures, evaluations, and outcome assessments
19. Participant has evidence of intraretinal hyperreflectivity by OCT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NT-501; Test product	Combination product: NT-501; Each NT-501 implant consisted of hCNTF-secreting NTC-201-6A.02 cells encapsulated within supportive matrices and surrounded by a semipermeable polymer membrane. The NTC-201-6A cells continuously secrete CNTF from the NT-501 implant into the vitreous cavity. Implanted by a qualified Health Care Professional.
Sham Comparator: Sham; A sham surgical procedure was performed to mimic the implant procedure; there was no comparator product.	Procedure: Sham Procedure; The sham surgery involved a superficial conjunctival incision performed under local anesthetic and closure with a single suture.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Rate of Change in the Area of EZ Area of Loss From Baseline Through Month 24	The rate of change in the area of EZ loss (IS/OS; macular photoreceptor loss) from baseline through month 24, as assessed using SD-OCT in the study eye of subjects with MacTel.	End point timeframe is through Month 24. Baseline, Month 6, 12, 16, 20 and 24. Month 6 was collected but not included in the primary analyses.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Aggregate Retinal Sensitivity Loss and Aggregate Interpolated Retinal Sensitivity Loss by Microperimetry (mITT Population)	Change from baseline in retinal sensitivity loss as measured by as measured by Macular Integrity Assessment (MAIA)	Baseline through 24 months.
Monocular Reading Speed (mITT Population)	Change from baseline through Month 24 for Monocular reading speed assessed using International Reading Speed Texts (IReST) cards developed by the IReST Study Group 21	Baseline through 24 months.

Collaborators and Investigators

• Sponsor: Neurotech Pharmaceuticals
• Collaborators: The Lowy Medical Research Institute Limited
• Investigators: Principal Investigator: Paul S Bernstein, MD, University of Utah - John A. Moran Eye Center

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2017
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): September 23, 2022

Study Registration Dates

• First Submitted: October 3, 2017
• First Submitted That Met QC Criteria: October 19, 2017
• First Posted (Actual): October 20, 2017

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: August 28, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Ciliary Neurotrophic Factor (CNTF); MacTel; Macular Telangiectasia Type 2
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Telangiectasis
• Other Study ID Numbers: NTMT-03-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes