Neovascular age-related macular degeneration (nAMD) Diabetic Macular edema (DME) MedDRA version: 20.1 Level: LLT Classification code 10057934 Term: Diabetic macular edema System Organ Class: 100000004853 MedDRA version: 20.0 Level: LLT Classification code 10075568 Term: Wet age-related macular degeneration System Organ Class: 100000004853
Conditions
Interventions
Product Name: TGF-ß2 Antisense
Product Code: ISTH0036
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: NA
CAS Number: NA
Other descriptive name: TGF-?2 ISOFORM SPECIFIC ANT
Sponsors
Isarna Therapeutics GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients must provide written informed consent before any study related procedures are performed 2.Patients must be =18 yrs in the DME cohort and = 50 in the nAMD cohort at Screening Study eye nAMD: 3. Active CNV lesions secondary to nAMD (including retinal angiomatous proliferation lesions with a CNV component) in the study eye at Screening in treatment naïve nAMD arm. 4. About 50% of the patients in the AMD treatment naïve group should have classic or predominantly classic CNV / Type II CNV or hemorrhage 5. Pretreated CNV lesions secondary to nAMD (including retinal angiomatous proliferation lesions with a CNV component) in the study eye at Screening in pretreated nAMD. About 50% of the patients should be included with SHRM present on OCT despite anti-VEGF therapy or hemorrhage present at initial diagnosis/ therapy start 6. Intra- and/or subretinal fluid affecting the central subfield of the study eye at Screening with CMT =305 µm in women, and =320µm in men or with a center point thickness of >260 in women and >270 micrometer in men as measured by SD-OCT in treatment naïve nAMD arm 7. For treatment naïve patients, BCVA between 83 and 23 letters, inclusive, in the study eye at Screening and Baseline using early treatment diabetic retinopathy study (ETDRS) testing. 8. For Treatment naïve and VEGF primed group: Treatment naïve nAMD in study eye 9. For VR-group: Dry or =50 micrometer SRF in vertical extension after receiving 1-6 anti-VEGF injections. Diagnosis no longer than 9 months before Baseline Study eye DME: 10. Active CME secondary to diabetes in the study eye at Screening in treatment naïve DME. 11. Intra- and/or subretinal fluid affecting the central subfield of the study eye at Screening with CMT =305 µm in women, and =320µm in men or with a center point thickness of >260 in women and >270 micrometer in men as measured by SD-OCT in treatment naïve DME arm. 12. For treatment naïve patients, BCVA between 83 and 23 letters, inclusive, in the study eye at Screening and Baseline using early treatment diabetic retinopathy study (ETDRS) testing. 13. Moderate to severe NPDRP assessed via ETDRS severity scale and mild PDRP (with 1 NVE) in study eye (diabetic retinopathy severity scale DRSS 43-61) 14. Absence of prior PRP treatment 15. For Treatment naïve group: Treatment naïve DME in study eye 16. For VR-group: History of CME secondary to diabetes in the study eye with complete resolution of IRF and/or SRF or a =20% reduction in CMT secondary to diabetes after receiving 1-6 monthly anti-VEGF injections over the last 9 months Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1.Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in either eye at BL 2.Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA 25 mmHg on medication or according to the investigator’s judgment at Scr or BL 11.Aphakia and/or complete of the posterior capsule in the study eye at Scr 12.For Treatment naïve and VEGF primed group:Any prior treatment for nAMD in study eye 13.For VR-group: > 50 micrometer SRF in vertical extension after receiving 1-6 anti-VEGF injections over the last 9 mon 14.For VR-group: > 6 anti-VEGF injections 15.Treatment requiring DME diagnosed for more than 9 mon 16.Poor quality of SD-OCT images 17.Focal laser scars within the central 1 mm ETDRS subfield 18.Concomitant conditions or ocular disorders in the study eye, including retinal diseases other than DME, that, in the judgment of the investigator, could require medical or surgical intervention during the study to prevent or treat visual loss that might result from that condition, or that limits the potential to gain visual acuity upon treatment with the investigational product 19.Structural damage within 0.5-disc diameter of the center of the macula in the study eye, e.g., vitreomacular traction, epiretinal membrane, retinal pigment epithelium (RPE) rip/tear scar, laser burn, at the time of Scr that in the investigator’s opinion could preclude visual function improvement with treatment 20.Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior BL 21.Uncontrolled glaucoma in the study eye defined as IOP > 25 mmHg on medication or according to the investigator’s judgment at Scr or BL 22.Moderate and severe PDRP requiring PRP in study eye 23.Prior PRP treatment in study eye 24.Aphakia and/or complete of the posterior capsule in the study eye at Scr 25.For Treatment naïve group: Any prior treatment for DME in study eye 26.For VR-group: 6 anti-VEGF inje
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate preliminary efficacy of ISTH0036 administered with intravitreal injections on central macular thickness (CMT) in patients with nAMD and DME that are treatment naïve or that are pretreated with aflibercept. Two different patient populations with nAMD and DME will be enrolled: Newly diagnosed, treatment naïve patients and patients that were diagnosed not more than 9 months ago and which received up to 6 initial anti-VEGF injections. In nAMD an additional group of patients who is initially primed with 1 single aflibercept injection will be assessed;Secondary Objective: •To evaluate the safety and tolerability of ISTH0036 monotherapy or in combination with aflibercept rescue treatment •To evaluate the effects of ISTH0036 in monotherapy or in combination with aflibercept rescue treatment on best corrected visual acuity (BCVA) •To evaluate the effects of ISTH0036 in monotherapy or with aflibercept rescue treatment on central macular volume •To evaluate the effects of ISTH0036 in monotherapy or with aflibercept rescue treatment on the extent of fibrosis and subretinal hyperreflective material visualized on OCT and multicolor images •To evaluate the effects of ISTH0036 in monotherapy or with aflibercept rescue treatment on the regression of DRP severity and ischemia. ;Primary end point(s): •OCT CMT at 7 months vs. baseline;Timepoint(s) of evaluation of this end point: Visit 9 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Number and type of adverse events (AE) in all groups • Incidence and progression of cataract using LOCS score in patients treated with ISTH0036 • Change in BCVA from baseline up to month 9 • Change of macular volume up to month 9 • Percentage of patients with IRF and/or SRF from Baseline to Month 7. • Change in OCT-A features assessed by qualitative criteria from baseline to Month 7 ;Timepoint(s) of evaluation of this end point: Visit 9, Visit 11 | — |
Countries
Austria, India
Contacts
Public ContactDr. Marion Munk
Isarna Therapeutics GmbH
Outcome results
None listed