Clinical trial NCT03316300: A Study to Determine the Safety and Efficacy of NT-501 in Macular Telangiectasia Type 2 - Protocol A
Official title: A Phase III Multicenter Randomized, Sham Controlled, Study to Determine the Safety and Efficacy of NT-501 in Macular Telangiectasia Type 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Macular Telangiectasia Type 2 (MacTel)
Keywords: Ciliary Neurotrophic Factor (CNTF)
Macular Telangiectasia Type 2
MacTel
Lead sponsor: Neurotech Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: The Lowy Medical Research Institute Limited
First posted: 2017-10-20
Enrollment: 120
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After confirming eligibility in conjunction with the reading center, the study eye of each subject was randomized (1:1) to either have NT-501 implanted or to undergo the sham procedure.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The Rate of Change in the Area of EZ Area of Loss From Baseline Through Month 24
timeFrame: 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 outcomes:
measure: Mean Change in Aggregate Retinal Sensitivity Loss and Aggregate Interpolated Retinal Sensitivity Loss by Microperimetry (mITT Population)
timeFrame: Baseline through 24 months.
measure: Monocular Reading Speed (mITT Population)
timeFrame: Baseline through 24 months.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic Medical Group
state: California
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute / David Geffen School of Medicine
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute at Stanford University
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado, P.C.
state: Colorado
city: Metairie
country: United States
facility: Retina Associates of New Orleans
state: Louisiana
city: Bethesda
country: United States
facility: National Institute of Health, NIH
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Royal Oak
country: United States
facility: Associated Retinal Consultants, P.C.
state: Michigan
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Cleveland
country: United States
facility: Retina Associates of Cleveland, Inc.
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Retina Consultants
state: Oklahoma
city: Portland
country: United States
facility: Retina Northwest, PC
state: Oregon
city: Knoxville
country: United States
facility: Southeastern Retina Associates, PC
state: Tennessee
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah John A. Moran Eye Center
state: Utah
city: Perth
country: Australia
facility: Lions Eye Institute
state: Western Australia
city: Paris
country: France
facility: Lariboisiere Hospital
city: Oxford
country: United Kingdom
facility: Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust
state: Oxfordshire
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
Study officials:
affiliation: University of Utah - John A. Moran Eye Center
name: Paul S Bernstein, MD
role: PRINCIPAL_INVESTIGATOR
References: