A Study Investigating the Efficacy and Safety of Intravitreal Injections of ANX007 in Patients With Geographic Atrophy

• ANX007 (Drug): Form: solution for injection; Route of Administration: IVT
• Sham comparator (Other): Form and Route of Administration: pressure to mimic IVT injection

Primary outcomes

• Rate of Change (Slope) From Baseline to Month 12 in GA Lesion Area [Baseline to Month 12]: GA lesion area was assessed by fundus autofluorescence (FAF) imaging, by an independent central reading center for GA lesion area. A linear mixed effect (LME) model was used to analyze the rate of change from baseline to Month 12 GA lesion area (mm2) for all groups. The model included fixed effects of treatment, time point, treatment by time point interaction, baseline GA lesion area, baseline GA lesion area by timepoint interaction, and baseline lesion multifocality. A random intercept for participant ID and a random slope for timepoint are included to account for repeated measurements for participants. The GA lesion area was analyzed as reported (that is, not transformed).

Secondary outcomes

• Change From Baseline to Month 12 in GA Lesion Area [Baseline to Month 12]: GA lesion area was assessed by fundus autofluorescence (FAF) imaging, by an independent central reading center for GA lesion area.
• Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Baseline to Month 12]: An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the investigational medicinal product. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse events module.
• Change From Baseline to Month 12 in Best Corrected Visual Acuity (BCVA) [Baseline to Month 12]: BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score on a test chart at a starting distance of 4 meters at each study visit. BCVA scores range from 0 to 100 letters with a higher score indicating a better vision.
• Number of Events With Confirmed ≥ 15-Letter Loss BCVA Decline [Baseline to Month 12]: Confirmed ETDRS BCVA ≥15-letter loss was defined as ≥15-letter loss observed for 2 consecutive visits. BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score on a test chart at a starting distance of 4 meters at each study visit. BCVA scores range from 0 to 100 letters with a higher score indicating a better vision.
• Change From Baseline to Month 12 in LLVA [Baseline to Month 12]: LLVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score on a test chart at a starting distance of 4 meters at each study visit. BCVA scores range from 0 to 100 letters with a higher score indicating a better vision.
• Number of Events With ≥ 15-Letter Loss LLVA Decline [Baseline to Month 12]: LLVA ≥15-letter loss worsening from Baseline during the 12-month Treatment. LLVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score on a test chart at a starting distance of 4 meters at each study visit. BCVA scores range from 0 to 100 letters with a higher score indicating a better vision.
• Change From Baseline to Month 12 in LLVD [Baseline to Month 12]: LLVD as assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score on a test chart at a starting distance f 4 meters at each study visit. LL-VD will be derived by subtracting LL-BCVA from BCVA.
• Number of Events With ≥ 15-Letter Loss LLVD Decline [Baseline to Month 12]: LLVD ≥15-letter loss worsening from Baseline during the 12-month Treatment. LLVD was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score on a test chart at a starting distance of 4 meters at each study visit. BCVA scores range from 0 to 100 letters with a higher score indicating a better vision.

Sex: All, ages: 50 Years to any

Inclusion Criteria:

* Diagnosis of geographic atrophy of the macula secondary to age-related macular degeneration as determined by the Investigator and confirmed by the Central Reading Center.
* GA lesion must have the following characteristics as determined by the independent Central Reading

Center based on assessment of FAF imaging at screening:

1. Well-demarcated GA with a total area (baseline lesion size) ≥2.5 millimeter squared (mm\^2) and

   * 17.5 mm\^2.
2. If GA is multifocal, at least 1 focal lesion must measure ≥1.25 mm\^2 with the overall aggregate area of GA as specified above.
3. Presence of hyper autofluorescence, any pattern, in the junctional zone of the GA. Absence of hyper autofluorescence (that is, pattern = none) is exclusionary.
4. The entire GA lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any peripapillary atrophy.

   * Normal luminance BCVA of 24 to 83 letters, inclusive, using ETDRS charts (20/25 to 20/320 Snellen equivalent, inclusive).
   * A female participant is eligible if she is not pregnant or breastfeeding and is a woman of non-childbearing potential or is using a contraceptive method that is highly effective, with a failure rate of <1% during the study intervention period and for at least 30 days after the last dose of study intervention.

Exclusion Criteria:

* Geographic atrophy due to other causes than AMD such as Stargardt disease, cone-rod dystrophy, pathologic myopia, or toxic maculopathies (for example, plaquenil maculopathy) in either eye.
* Any evidence of choroidal neovascularization (CNV) in the study eye:

  1. Any history of CNV of any cause based on medical history.
  2. Evidence of prior or active CNV or related findings (for example, retinal pigment epithelial rips or tears) based on FAF, Spectral Domain Optical Coherence Tomography (SD-OCT) imaging, intravenous fluorescein angiography (IVFA) and color fundus photo as assessed by the Central Reading Center.
* Spherical equivalent of -8.00 diopters (D) myopia or higher in the study eye.
* Uncontrolled glaucoma in the study eye (Intraocular pressure \[IOP\] >25 mmHg despite treatment with anti- glaucoma medication) or history of neovascular glaucoma.
* History of glaucoma filtration surgery, minimally-invasive glaucoma surgery involving an implant, or vitrectomy surgery, or other procedure in the study eye that could affect drug distribution and/or clearance.
* Any current or prior ocular disease, other than geographic atrophy, that in the opinion of the Investigator could interfere with the conduct of the study including, but not limited to, insufficient pupil dilation, retinal or optic nerve disease, media opacity, or aphakia in the study eye.
* History of any prior IVT treatment for any indication in the study eye.
* Any prior treatment for AMD in the study eye (for example, surgical, radiation, thermotherapeutic, or laser intervention), except oral supplements or minerals.

Participant flow

Outcome results

• Rate of Change (Slope) From Baseline to Month 12 in GA Lesion Area (Primary), Mean, mm^2/year: ANX007 EM 1.9902 +/- 0.36343; ANX007 EOM 2.1575 +/- 0.34824; ANX007 Pooled 2.0837 +/- 0.30177; Sham 1.9019 +/- 0.34239 (p 0.5503)
• Change From Baseline to Month 12 in GA Lesion Area (Secondary), Least squares mean, mm^2: ANX007 EM 2.3547 +/- 0.26452; ANX007 EOM 2.5782 +/- 0.24317; ANX007 Pooled 2.4835 +/- 0.18003; Sham 2.3170 +/- 0.23142
• Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Secondary), Count of participants, Participants: ANX007 EM 65; ANX007 EOM 68; Sham 68
• Change From Baseline to Month 12 in Best Corrected Visual Acuity (BCVA) (Secondary), Mean, Number of letters read correctly: ANX007 EM -1.7 +/- 1.33; ANX007 EOM -2.6 +/- 1.29; Sham -4.1 +/- 1.31
• Number of Events With Confirmed ≥ 15-Letter Loss BCVA Decline (Secondary), Number, Number of Events: ANX007 EM 4; ANX007 EOM 8; Sham 15
• Change From Baseline to Month 12 in LLVA (Secondary), Least squares mean, Number of letters read correctly: ANX007 EM -1.4 +/- 1.29; ANX007 EOM -2.8 +/- 1.25; Sham -4.8 +/- 1.31
• Number of Events With ≥ 15-Letter Loss LLVA Decline (Secondary), Number, Number of Events: ANX007 EM 6; ANX007 EOM 8; Sham 16
• Change From Baseline to Month 12 in LLVD (Secondary), Least squares mean, Number of letters read correctly: ANX007 EM -0.4 +/- 1.55; ANX007 EOM 1.3 +/- 1.50; Sham 0.6 +/- 1.57
• Number of Events With ≥ 15-Letter Loss LLVD Decline (Secondary), Number, Number of Events: ANX007 EM 4; ANX007 EOM 8; Sham 13

Adverse events

Time frame: Up to 12 months

Serious adverse events by term

10 more terms not shown.

Other adverse events by term

• Results publication: Tzoumas N, Riding G, Williams MA, Steel DH. Complement inhibitors for age-related macular degeneration. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD009300. doi: 10.1002/14651858.CD009300.pub3. PMID 37314061

• Study Protocol (PDF, 2022-10-28)
• Statistical Analysis Plan (PDF, 2023-05-01)

• Clinical Trials, Study director, Annexon, Inc.