Phase IIa study to evaluate the efficacy of the ISTH0036 in treatment naive and previously treated patients with Macular Degeneration and Diabetic Macular Edema

Phase 2

• Conditions: Health Condition 1: E133- Other specified diabetes mellituswith ophthalmic complications

• Registration Number: CTRI/2022/04/041823
• Lead Sponsor: Isarna Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 17 October 2022

Recruitment & Eligibility

• Status: ot Yet Recruiting
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

Patients eligible for inclusion in this study must meet all the following 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 na�¯ve nAMD arm.

4. About 50% of the patients in the AMD treatment na�¯ve 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 â�¥305 �¼m in women, and â�¥320�¼m in men or with a center point thickness of >260 in women and >270 micrometer in men as measured by SD-OCT in treatment na�¯ve nAMD arm.

7. For treatment na�¯ve 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 na�¯ve and VEGF primed group: Treatment na�¯ve 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 na�¯ve DME.

11. Intra- and/or subretinal fluid affecting the central subfield of the study eye at Screening with CMT â�¥305 �¼m in women, and â�¥320�¼m in men or with a center point thickness of >260 in women and >270 micrometer in men as measured by SD-OCT in treatment na�¯ve DME arm.

12. For treatment na�¯ve 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 na�¯ve group: Treatment na�¯ve 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.

Exclusion Criteria

Patients meeting any of the following criteria are not eligible for inclusion in this study.

Ocular conditions

1. Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in either eye at Baseline.

2. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 35 ETDRS letters at Screening (except when due to conditions whose surgery may improve visual acuity, e.g., cataract).

Study eye nAMD

3. nAMD diagnosed for more than 9 months

4. Poor quality of SD-OCT images at Screening or Baseline.

5. Central subfield of the study eye affected by geographic atrophy assessed by OCT, color fundus photography (CFP) and fundus autofluorescence (FAF) at Screening.

6. Subretinal blood affecting the central subfield and/or � 50% of the lesion of the study eye at Screening.

7. Concomitant conditions or ocular disorders in the study eye, including retinal diseases other than nAMD, 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.

8. 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 Screening that in the investigatorââ?¬•s opinion could preclude visual function improvement with treatment.

9. Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline.

10. Uncontrolled glaucoma in the study eye defined as IOP > 25 mmHg on medication or according to the investigatorââ?¬•s judgment at Screening or Baseline.

11. Aphakia and/or complete absence of the posterior capsule in the study eye at Screening.

12. For Treatment na�¯ve 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 months

14. For VR-group: > 6 anti-VEGF injections

Study eye DME

15. Treatment requiring DME diagnosed for more than 9 months

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 Screening that in the investigatorââ?¬•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 to Baseline.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
OCT CMT at 7 months vs. baseline. For treatment na�¯ve patients, improvement versus BL will be analyzed, for anti-VEGF pre-treated patients, maintenance, or improvement of CMT versus BL will be assessed.Timepoint: 9 Months

Secondary Outcome Measures

Name	Time	Method
umber and type of adverse events (AE) in all groups <br/ ><br>Incidence and progression of cataract using LOCS III score in patients treated with ISTH0036 <br/ ><br>Change in BCVA from baseline up to month 9 <br/ ><br>Change of central macular volume up to month 9 <br/ ><br>Timepoint: 9 Months