Macular Telangiectasia Type 2
Conditions
Keywords
Macular Telangiectasia Type 2, CNTF, Mactel
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).
Interventions
COMBINATION_PRODUCTNT-501 CNTF implant
Single implantation of CNTF-secreting NT-501 device into fellow (untreated) eye
Sponsors
The Lowy Medical Research Institute Limited
Neurotech Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events | 6 months | Assess the incidence and severity of adverse events (AEs) following bilateral ocular implantation of NT-501 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Levels of CNTF and Immunogenicity for NT-501 | 6 months | Incidence of positive serum levels of CNTF and immunogenicity for NT-501 with quantification of antibodies (Ab) to CNTF, neutralizing antibodies (NAb) to CNTF, Ab to NTC-201-6A cells, and Ab to mouse dihydrofolate reductase (mDHFR) at any time. |
Countries
Australia, United States
Participant flow
Recruitment details
Of the 33 enrolled subjects, 32 (97.0%) received NT-501; the exception was a subject whose surgery was canceled due to an event of arterial fibrillation that occurred prior to surgery and resulted in subject discontinuation. No subject had NT-501 removed from either eye during the study, and all 32 subjects who received NT-501 in this study completed the study.
Pre-assignment details
Eligible subjects must have had a positive diagnosis of MacTel and previously received NT-501 in one 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). Subjects who participated in the Phase 3 study must have completed the Month 24 visit in that study and subjects enrolled in either the Phase 1/2 extension study or the Phase 3 study must have discontinued prior to enrollment in the current study.
Participants by arm
| Arm | Count |
|---|---|
| NT-501 in Fellow Eye NT-501 was implanted on Day 0 in the fellow eye of subjects who received a single NT-501 in a previous study; subjects were followed for 6 months post-implantation of NT-501 in this study.
NT-501 CNTF implant: Single implantation of CNTF-secreting NT-501 device into fellow (untreated) eye | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | NT-501 in Fellow Eye |
|---|---|
| Age, Customized 50 to < 60 years | 9 Participants |
| Age, Customized 60 to < 70 years | 17 Participants |
| Age, Customized Age (Years) | 63.0 years STANDARD_DEVIATION 6.55 |
| Age, Customized > or = to 70 years | 6 Participants |
| BCVA (letters) for Study Eye Fellow Eye | 70.1 letters correctly read STANDARD_DEVIATION 9.58 |
| BCVA (letters) for Study Eye Study Eye | 68.7 letters correctly read STANDARD_DEVIATION 11.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 26 / 32 |
| serious Total, serious adverse events | 2 / 32 |
Outcome results
Primary
Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events
Assess the incidence and severity of adverse events (AEs) following bilateral ocular implantation of NT-501
Time frame: 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NT-501 in Fellow Eye | Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events | At least 1 TEAE | 26 Participants |
| NT-501 in Fellow Eye | Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events | At least 1 ocular TEAE in study eye | 26 Participants |
| NT-501 in Fellow Eye | Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events | At least 1 ocular TEAE in fellow eye | 6 Participants |
| NT-501 in Fellow Eye | Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events | At least 1 nonocular TEAE | 13 Participants |
| NT-501 in Fellow Eye | Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events | At least 1 treatment related ocular TEAE | 26 Participants |
| NT-501 in Fellow Eye | Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events | At least 1 treatment related nonocular TEAE | 0 Participants |
| NT-501 in Fellow Eye | Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events | At least 1 SAE | 2 Participants |
| NT-501 in Fellow Eye | Frequency of Ocular and/or Non-ocular Treatment Emergent Adverse Events | NT-501 removal from either eye | 0 Participants |
Secondary
Serum Levels of CNTF and Immunogenicity for NT-501
Incidence of positive serum levels of CNTF and immunogenicity for NT-501 with quantification of antibodies (Ab) to CNTF, neutralizing antibodies (NAb) to CNTF, Ab to NTC-201-6A cells, and Ab to mouse dihydrofolate reductase (mDHFR) at any time.
Time frame: 6 months
Population: A neutralizing antibody test to NT-501-produced CNTF was performed to verify or refute CNTF antibody detected in one participant. The neutralizing antibody test refuted that the antibody detected was to NT-501 CNTF.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NT-501 in Fellow Eye | Serum Levels of CNTF and Immunogenicity for NT-501 | CNTF Positive | 0 Participants |
| NT-501 in Fellow Eye | Serum Levels of CNTF and Immunogenicity for NT-501 | Ab Positive to CNTF | 1 Participants |
| NT-501 in Fellow Eye | Serum Levels of CNTF and Immunogenicity for NT-501 | Neutralizing Ab to CNTF | 0 Participants |
| NT-501 in Fellow Eye | Serum Levels of CNTF and Immunogenicity for NT-501 | Ab to NTC | 0 Participants |
| NT-501 in Fellow Eye | Serum Levels of CNTF and Immunogenicity for NT-501 | ab to DHRF | 0 Participants |