A Phase 4, Multicenter, Open-label Study to Evaluate Long-term Safety and Efficacy of Revakinagene Taroretcel-Lwey (NT-501) Previously Implanted During a Phase 1, Phase 2, or Phase 3 Clinical Study and to Evaluate NT-501 Implanted in Participants Who Underwent the Sham Procedure in a Phase 3 Clinical Study of Macular Telangiectasia Type 2 (MacTel)
Trial Snapshot
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- Enrollment
- 234
- Locations
- 59
- Primary Endpoint
- Incidence of ocular and nonocular adverse events (AEs) and serious adverse events (SAEs)
Study Overview
Brief Summary
The purpose of this global, multicenter, open-label, Phase 4 clinical extension study is to evaluate the long-term safety and efficacy of revakinagene taroretcel-lwey (Encelto™; hereinafter referred to as NT-501), in participants with macular telangiectasia type 2 (MacTel) who previously received the intraocular implant in a Phase 1, Phase 2, or Phase 3 clinical study and have retained at least 1 NT-501 at study entry. In addition, this study will evaluate the safety and efficacy of NT501 in participants who previously underwent the sham procedure in a Phase 3 MacTel clinical study and elect to have NT-501 implanted intraocularly in this Phase 4 study.
Detailed Description
This extension study consists of 3 arms:
- Arm 1 (Phase 3 Treated Participants' Long-term Follow-up): Arm 1 is to assess the long-term safety and efficacy of NT-501 in participants who received NT-501 in a previous MacTel Phase 3 clinical study (NTMT-03-A or NTMT-03-B) and have retained at least 1 NT-501at study entry.
- Arm 2 (Phase 1 and Phase 2 Long-term Follow-up): Similar to Arm 1, Arm 2 is to assess the long-term safety of NT-501 in participants who received NT-501 in a previous MacTel Phase 1 or Phase 2 clinical study (NTMT-01, NTMT-02, or NTMT-01/02E) and have retained at least 1 NT-501 at study entry.
- Arm 3 (Phase 3 Sham to Implant Crossover): Arm 3 will evaluate the safety and efficacy of NT-501 in participants who previously underwent the sham procedure in a Phase 3 MacTel clinical study (NTMT-03-A or NTMT-03-B) and elect to have NT-501 implanted intraocularly in this extension study.
Arms 1 and 2 are noninterventional and observational studies. For participants who previously received a single NT-501 implant, the implanted eye is designated the study eye. For participants who received an NT-501 in both eyes (ie, the first implant received in NTMT-01, NTMT-02, NTMT-01/02E, NTMT-03A, or NTMT-03B, and the second implant received in NTMT-02B), both eyes will be designated as study eyes.
Only participants in Arm 3 will receive active intervention during this Phase 4 study. A participant can receive NT-501 in either eye that meets eligibility criteria according to investigator assessment, and in accordance with participant choice. However, if only 1 eye is eligible for implantation based on all inclusion/exclusion criteria, then that eye will be selected for NT-501 implantation. The eye selected for NT-501 implantation will be designated as the study eye.
Regardless of study eye designation, both eyes of each participant in all 3 study arms will be evaluated during the study.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •To be eligible to participate in this study, an individual participant must meet all the following criteria:
- •Male or female adult participants who previously completed an NT-501 MacTel clinical study and:
- •Arm 1: received NT-501 intraocular implant in either Phase 3 study (NTMT-03-A or NTMT-03-B) and have retained at least 1 NT-501 at study entry.
- •Arm 2: received NT-501 intraocular implant in the Phase 1 study (NTMT-01), Phase 2 study (NTMT-02), or in the substudy of the Phase 1 and Phase 2 extension study (NTMT-01/02E) and have retained at least 1 NT-501 at study entry.
- •Note: participants who received NT-501 in both eyes (ie, participated in study NTMT-02B) will be enrolled in either Arm 1 or Arm 2 based on the study in which the first NT 501 was implanted (ie, participants who received the first implant in a Phase 3 study will be enrolled in Arm 1 and those who received the first implant in the Phase 1 study or Phase 2 study will be enrolled in Arm 2).
- •Arm 3: underwent the sham procedure in either Phase 3 study (NTMT-03-A or NTMT-03-B)
- •Participant or their legally authorized representative must be able to provide written informed consent to participate in the study, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, and local regulations, before initiating any clinical study related procedures.
- •Arm 3: female participants of childbearing potential must agree to use highly effective contraception. Highly effective forms of contraception (generally a first-year typical use pregnancy risk of 1% or less) include the following: contraceptive implants; an intrauterine device; permanent contraceptive procedures (vasectomy, bilateral salpingectomy, bilateral tubal occlusion, or partial salpingectomy); abstinence. A combination of male condom with either cap, diaphragm, or sponge with spermicide (ie, double barrier methods) is also considered an acceptable, but not highly effective, method of birth control.
Exclusion Criteria
- •To participate in this study, the potential participant must not meet any of the following criteria. (Note that the ocular exclusion criteria are relevant to the study eye[s], unless indicated for both eyes):
- •Exclusion Criteria Applicable to Arms 1, 2, and 3:
- •Participant is medically unable to comply with clinical study procedures or visits.
- •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.
- •Participant has undergone explantation of NT-501 prior to screening. Note: A participant who received bilateral implants and underwent explantation in only 1 eye prior to screening may be enrolled in the study.
- •Participant received Encelto commercial implant in the fellow eye, if applicable, less than 3 months prior to study screening.
- •Exclusion Criteria Applicable to Arm 3 Only:
- •Participant has significant corneal or media opacities in the study eye to be implanted.
- •Participant has evidence of pathologic myopia in the study eye to be implanted.
- •Participant has any of the following lens opacities in the study eye to be implanted: 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. Note: the participant can be reconsidered for enrollment 90 days after undergoing cataract surgery.
- •Participant has undergone lens removal in the study eye to be implanted in the previous 3 months or YAG laser within 4 weeks of the screening/baseline visit.
- •Participant has evidence of ocular disease in the study eye to be implanted 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).
- •Received intravitreal steroid therapy in the study eye to be implanted within 6 months prior to screening.
- •Evidence of active exudative intraretinal neovascularization or subretinal neovascularization in the study eye to be implanted, as evidenced by hemorrhage, hard exudate, subretinal fluid, or intraretinal fluid.
- •Evidence of central serous chorioretinopathy in the study eye to be implanted within 3 months prior to screening.
- •A history of ocular herpes virus in the study eye to be implanted.
- •Participant is on chemotherapy.
- •Participant is pregnant or breastfeeding.
- •Participation in any other clinical study of an intervention (drug or device) within 6 months prior to the screening/baseline visit.
- •A history of malignancy that would compromise survival during the clinical study.
Arms & Interventions
Arm 2 (Phase 1 and Phase 2 Long-term Follow-up)
For participants who received NT-501 (ENCELTO) in a previous Phase 1 study (NTMT-01), Phase 2 study (NTMT-02), in the sub study of Phase 1 and Phase 2 extension study (NTMT-01/02E), or for participants who received NT-501 (ENCELTO) in both eyes (i.e. participated in study NTMT-02B) but received the first NT-501 (ENCELTO) implant in a Phase 1 or Phase 2 study. No new treatment intervention will be administered. Arm 2 is focused on long term follow-up for participant who already has the ENCELTO implant at time of study screening and enrollment.
Intervention: NT-501/revakinagene taroretcel-lwey (Combination Product)
Arm 1 (Phase 3 Long-term Follow-up)
For participants who received NT-501 (ENCELTO) in a previous Phase 3 study (NTMT-03-A or NTMT-03-B), or for participants who received NT-501 (ENCELTO) in both eyes (i.e. participated in study NTMT-02B) but received the first NT-501 (ENCELTO) implant in a Phase 3 study. No new treatment intervention will be administered. Arm 1 is focused on long term follow-up for participant who already has the ENCELTO implant at time of study screening and enrollment.
Intervention: NT-501/revakinagene taroretcel-lwey (Combination Product)
Arm 3 (Phase 3 Sham to Implant Crossover)
For participants who underwent Sham procedure in either Phase 3 study (NTMT-03-A or NTMT-03-B) and will receive NT-501 in this study.
Intervention: NT-501/revakinagene taroretcel-lwey (Combination Product)
Outcomes
Primary Outcomes
Incidence of ocular and nonocular adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Baseline and annually for up to 5 yrs for Arms 1 and 2 and baseline, perioperative, and annually for up to 5 yrs for Arm 3 participants
Incidence of ocular and nonocular adverse events (AEs) and serious adverse events (SAEs)
Percentage of participants with a loss of 15 letters or more in best corrected visual acuity (BCVA) compared to presurgery baseline BCVA
Time Frame: Baseline and annually for up to 5 yrs for Arms 1 and 2 and baseline, perioperative, and annually for up to 5 yrs for Arm 3 participants
Percentage of participants with a loss of 15 letters or more in best corrected visual acuity (BCVA) compared to presurgery baseline BCVA using the Early Treatment Diabetic Retinopathy Study (ETDRS) distance chart
Secondary Outcomes
- Change from presurgery baseline in ellipsoid zone (EZ) area loss(Baseline and annually for up to 5 yrs for Arms 1 and 2 and baseline, perioperative, and annually for up to 5 yrs for Arm 3 participants)
- Change from presurgery baseline in BCVA(Baseline and annually for up to 5 yrs for Arms 1 and 2 and baseline, perioperative, and annually for up to 5 yrs for Arm 3 participants)
- Change from presurgery baseline in aggregate retinal sensitivity(Baseline and annually for up to 5 yrs for Arms 1 and 2 and baseline, perioperative, and annually for up to 5 yrs for Arm 3 participants)
- Change from presurgery baseline in monocular reading speed(Baseline and annually for up to 5 yrs for Arms 1 and 2 and baseline, perioperative, and annually for up to 5 yrs for Arm 3 participants)
- Change from presurgery baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25)(Baseline and annually for up to 5 yrs for Arms 1 and 2 and baseline, perioperative, and annually for up to 5 yrs for Arm 3 participants)