COMBINATION OF TWO ADENO-ASSOCIATED VIRAL VECTORS OF SEROTYPE 8 CONTAINING THE 5'- AND THE 3'- HALF CODING SEQUENCES OF HUMAN ABCA4 FUSED TO INTEINS for Stargardt disease (STGD1)

Inclusion criteria

• {"criterion_text":"- Presence of biallelic mutation in ABCA4 with 2 or more pathogenic or likely pathogenic variants confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory."}
• {"criterion_text":"- Part A: aged ≥18 years to ≤55 years inclusive"}
• {"criterion_text":"- Part B: aged ≥8 years to ≤55 years inclusive"}
• {"criterion_text":"- Participants must have adequate clarity of ocular media and adequate pupillary dilation to permit good quality imaging of macular atrophy in the trial eye (TE), as determined by the Investigator"}
• {"criterion_text":"- TE meeting the following criteria: Part A o For sentinel participants: a low FAF signal in the macula must include macular atrophy with an area of DDAF ≥0.05mm2 and ≤13.5 mm2. 20/320 ≤BCVA ≤20/80 (25-55 letters) o For all other participants: Low FAF signal in the macula must include macular atrophy defined as DAF within ≥0.05mm2 and ≤13.5 mm2. 20/200≤BCVA ≤20/32 (35-75 letters) o For all participants: continuous absence of the EZ band (length of EZ loss) ≥500 microns in the fovea centered horizontal and/or vertical OCT line-scan. Part B o Low FAF signal in the macula with an area of DAF ≥0.05mm2 and ≤13.5 mm2 o 20/200≤BCVA ≤20/32 (35-75 letters). o Evidence of progression on OCT and/or FAF"}

Exclusion criteria

• {"criterion_text":"- Macular atrophy associated with a condition other than STGD1 in either eye"}
• {"criterion_text":"- DAF contiguous with area of peripapillary atrophy in the TE, as determined by the reading center"}
• {"criterion_text":"- Previously confirmed mutations in any of the following genes: ELOVL4, PROM1, PRPH2, CRX, BEST-1, CDH3, RPE65, PDE6A, PDE6B, RLBP1, RAB28, RDH11, RP25, DRAM-1, and MT-TL1"}
• {"criterion_text":"- Presence in either eye of ocular disease that in the opinion of the Investigator compromises or confounds visual function, including but not limited to, choroidal neovascularization, epiretinal membrane, moderate/severe diabetic retinopathy, diabetic macular edema, uveitis, other macular diseases."}
• {"criterion_text":"- Presence of moderate or severe glaucomatous optic neuropathy in the TE; uncontrolled (intraocular pressure [IOP]) despite the use of more than 2 topical agents; a history of glaucoma-filtering or valve surgery"}
• {"criterion_text":"- History of any intraocular or ocular surface surgery in either eye ≤3 months prior to Screening"}
• {"criterion_text":"- YAG laser capsulotomy is permitted if performed >3 weeks prior to Day 0"}
• {"criterion_text":"- History of any vitreoretinal surgery (scleral buckle, pars plana vitrectomy, retrieval of a dropped nucleus or intraocular lens (IOL), radial optic neurotomy, sheathotomy, and cyclodestructive procedures in the TE"}
• {"criterion_text":"- Retinal degeneration advanced beyond a point where reliable measurement of the integrity of the EZ on macular OCT is possible: participants will be excluded if any areas of EZ loss in the TE are not fully surrounded by intact or attenuated EZ within the fovea-centered 35 × 20 OCT scan, as assessed by the central reading center; diffuse or multifocal EZ loss without clear boundaries, or extending beyond the fovea-centered 35 × 20 OCT scan are not allowed."}

Primary endpoints

• {"endpoint_text":"- Part A: Incidence and severity of adverse events (AEs) including serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), dose limiting toxicities (DLTs), and changes in clinical laboratory parameters, vital signs, physical examination findings and immunogenicity parameters from Day 0 to End of Trial","definition_or_measurement_approach":"Recorded incidence and severity of AEs/SAEs/TEAEs/DLTs and changes in clinical laboratory parameters, vital signs, physical exam findings and immunogenicity parameters from Day 0 to End of Trial (timeframe and parameters specified in endpoint text)."}
• {"endpoint_text":"- Part B: Rate of change of area of ellipsoid zone (EZ) loss at 12 months","definition_or_measurement_approach":"Rate of change of area of ellipsoid zone (EZ) loss measured at 12 months (measurement method not specified in the provided fields)."}

Secondary endpoints

• {"endpoint_text":"- Part A: Rate of change at 12, 24, and 60 months as measured by: Area of ellipsoid zone (EZ) loss, Area of atrophy as assessed via short wavelength fundus autofluorescence (SW-FAF), Macular sensitivity assessed via microperimetry, Best corrected visual acuity (BCVA) letter score, Low-luminance visual acuity (LLVA) letter score","definition_or_measurement_approach":"Measured at 12, 24, and 60 months using area of EZ loss, area of atrophy via SW-FAF, macular sensitivity via microperimetry, BCVA letter score, and LLVA letter score (methods and instruments as specified in protocol)."}
• {"endpoint_text":"- Part B: Incidence and severity of adverse events (AEs) including serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), dose limiting toxicities (DLTs), and changes in clinical laboratory parameters, vital signs, physical examination findings and immunogenicity parameters from Day 0 to End of Trial","definition_or_measurement_approach":"Recorded incidence and severity of AEs/SAEs/TEAEs/DLTs and changes in laboratory parameters, vital signs, physical exam findings and immunogenicity parameters from Day 0 to End of Trial."}
• {"endpoint_text":"- Part B: Rate of change at 12, 24, and 60 months as measured by: Area of ellipsoid zone (EZ) loss (24 and 60 months), Area of atrophy as assessed via short wavelength fundus autofluorescence (SW-FAF), Macular sensitivity assessed via microperimetry, Best corrected visual acuity (BCVA) letter score, Low-luminance visual acuity (LLVA) letter score","definition_or_measurement_approach":"Measured at specified timepoints using area of EZ loss (noted for 24 and 60 months), area of atrophy via SW-FAF, macular sensitivity via microperimetry, BCVA and LLVA letter scores."}

Italy

Earliest CTIS Part Ii Submission Date

14-01-2026

Latest Decision Or Authorization Date

14-04-2026

Processing Time Days

90

Number Of Sites

1

Number Of Participants

8

Belgium

Earliest CTIS Part Ii Submission Date

11-03-2026

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

30

Number Of Sites

1

Number Of Participants

3

Netherlands

Earliest CTIS Part Ii Submission Date

11-03-2026

Latest Decision Or Authorization Date

15-04-2026

Processing Time Days

35

Number Of Sites

1

Number Of Participants

6

Norway

Earliest CTIS Part Ii Submission Date

14-01-2026

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

89

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Aavantgarde Bio S.r.l.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

Ora Europe Limited

Responsibilities

Sponsor third-party roles/codes: 1,12,2,5,6,7,8 (as listed in CTIS record)

Third parties

• {"country":"United Kingdom","full_name":"Ora Europe Limited","duties_or_roles":"1,12,2,5,6,7,8","organisation_type":"Pharmaceutical company"}