Clinical trial NCT04729972: Safety Study to Evaluate Bilateral CNTF Implants in Subjects With MacTel Type 2
Official title: Phase II, Multicenter, Open-label Safety Study of Bilateral NT-501 in Participants With Macular Telangiectasia Type 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Macular Telangiectasia Type 2
Keywords: Macular Telangiectasia Type 2
CNTF
Mactel
Lead sponsor: Neurotech Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: The Lowy Medical Research Institute Limited
First posted: 2021-01-29
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multi-center, open-label, 6-month study to evaluate the safety of bilateral CNTF implants in participants with Macular Telangiectasia Type 2.

Detailed description: This was a multicenter, open-label study designed to evaluate the safety of bilateral NT-501 in subjects with MacTel. All subjects who received NT-501 in a single eye prior to or in the Phase 1/2 extension study (NTMT-01/02E) or in 1 of the 2 Phase 3 studies (NTMT-03-A or NTMT-03-B), and met all other eligibility criteria, qualified for participation in the current study; enrolled subjects underwent intraocular implantation of NT-501 in the fellow eye and were followed for 6 months. Note that, throughout this report, all references to "study eye" mean the eye that received NT-501 in the current study (ie, not the eye that was treated in the previous study).

Eligibility criteria: General Inclusion Criteria

1. Participants from the NTMT-03 study must have completed the Month-24 visit
2. Participant in the MacTel Phase 1/2 extension (NTMT-01/02E) study or the Phase 3 study must exit these studies prior to entering the Bilateral Implant safety study (NTMT-02B)
3. Participant must be willing and able to follow the study instructions and be willing and able to complete all required study procedures and visits
4. Participant must be willing and able to provide a signed Informed Consent, as well as written documentation in accordance with the relevant country and local privacy requirements, e.g., written data protection consent
5. Females of childbearing potential must consent to a pregnancy test before entering the study
6. A participant's refusal to allow the collection of blood samples for analysis of serum CNTF, serum Ab or Nab to CNTF, Ab to NTC-201.6A cells and Ab to DFHR levels in one eye will not exclude the participant from study participation

Ocular Inclusion Criteria

1. Participant must have a positive diagnosis of MacTel type 2 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 in the study eye
2. Participant must have steady fixation in the foveal or parafoveal area in the study eye and sufficiently clear media for good quality photographs

General Exclusion Criteria

1. Females of childbearing potential (those who are not surgically sterilized or post- menopausal, i.e., absence of menstruation for 12 months or longer) may not participate in the study if any of the following conditions exists:

   * Pregnant (positive pregnancy test at Visit 1 or intend to become pregnant during the study)
   * Nursing (lactating)
   * Do not agree to use adequate birth control methods for the duration of the study and until 90 days after the last administration of study drug (adequate birth control methods are: hormonal - oral, implantable, transdermal or injectable contraceptives; mechanical - spermicide in conjunction with a barrier such as condom or diaphragm, intrauterine device \[IUD\] or surgical sterilization of partner, or total sexual abstinence)
2. Participant is too ill to likely complete the entire study, based on the investigator's assessment
3. Participant, in the opinion of the investigator, is not suitable for study participation
4. Participant with any screening laboratory finding (serum chemistry, hematology, urinalysis) that in the opinion of the investigator is not suitable for study participation
5. Participant has a history or current evidence of severe hypersensitivity to the NT-501 implant
6. Participant has a history or current evidence of a medical condition (systemic or ophthalmic disease, metabolic dysfunction, physical examination finding or clinical laboratory finding) that may in the opinion of the investigator preclude the safe administration of the NT-501 implant or adherence to the scheduled study visits, safe participation in the study or affect the results of the study (e.g., unstable or progressive cardiovascular, cerebral vascular, pulmonary, Parkinson's, liver or renal disease; depression, cancer, or dementia

Ocular Exclusion Criteria

1. Participant has a history or evidence of the following surgeries/procedures in the study eye, as assessed at Visit 1, including:

   * Submacular surgery
   * Vitrectomy
   * Retinal detachment
   * Incisional glaucoma surgery
   * Trabeculectomy or trabeculoplasty
   * Cataract surgery or laser-assisted in situ keratomileusis (LASIK) performed in the previous 6 months
2. Participant has uncontrolled glaucoma; or ocular hypertension, i.e., IOP ≥ 25 mmHg in the study eye
3. Participant has evidence of intraretinal or subretinal neovascularization or central serous chorioretinopathy in the study eye
4. Participant has evidence of ocular disorder(s) in the study eye of a severity that could confound the interpretation of study results, compromise visual acuity or require medical or surgical intervention during the study period, including retinal vascular occlusion, severe nonproliferative or proliferative diabetic retinopathy, retinal detachment, macular hole, geographic atrophy, intraretinal or subretinal neovascularization, central serous chorio-retinopathy, pathological myopia
5. Participant has a vitreous hemorrhage in the study eye at Visit 1 (Screening)
6. Participant has a spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia
7. Participant has a history or evidence of penetrating ocular trauma in the study eye
8. Participant has an anticipated need for cataract extraction in the study eye within 6 months of Visit 1 (Screening) such as 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
9. Participant has uveitis, history of uveitis in either eye or history of ocular herpes virus in either eye
10. Participant has undergone major surgery within the last 6 months (systemic or ocular in either eye) or who are likely to require major surgery within 6 months of Visit 1 (Screening)
11. Participant has periocular or ocular/intraocular infection or inflammation in either eye (such as infectious conjunctivitis, keratitis, scleritis, endophthalmitis) within 3 months prior to Visit 1 (Screening)
12. Participant has ocular hypotension in either eye (\<6 mmHg) that in the opinion of the Investigator would interfere with the NT-501 implant insertion
13. Participant has a history of scleritis, scleral thinning, periocular, ocular, or intraocular infection or inflammation, cicatrizing conjunctival diseases any other ocular conditions in the study eye that could interfere with or complicate the surgery associated with NT-501implant insertion

Primary outcomes:
measure: Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events
timeFrame: 6 months
Secondary outcomes:
measure: Serum Levels of CNTF and Immunogenicity for NT-501
timeFrame: 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute
state: California
city: Washington
country: United States
facility: National Eye Institute
state: District of Columbia
city: Miami
country: United States
facility: Bascom Palmer
state: Florida
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary, Retina Service
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, Kellogg Eye Center
state: Michigan
city: Beachwood
country: United States
facility: Retina Associates of Cleveland, Inc.
state: Ohio
city: Houston
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Sydney
country: Australia
facility: Save Sight Institute
state: New South Wales
city: East Melbourne
country: Australia
facility: Centre for Eye Research Australia
state: Victoria
city: Nedlands
country: Australia
facility: Lions Eye Institute
state: Western Australia
Study officials:
affiliation: Neurotech Pharmaceuticals, LLC
name: Thomas Aaberg, Jr, MD
role: STUDY_DIRECTOR
References:
citation: Chew EY, Clemons TE, Jaffe GJ, Johnson CA, Farsiu S, Lad EM, Guymer R, Rosenfeld P, Hubschman JP, Constable I, Wiley H, Singerman LJ, Gillies M, Comer G, Blodi B, Eliott D, Yan J, Bird A, Friedlander M; Macular Telangiectasia Type 2-Phase 2 CNTF Research Group. Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial. Ophthalmology. 2019 Apr;126(4):540-549. doi: 10.1016/j.ophtha.2018.09.041. Epub 2018 Oct 4.