Annexin A5 for Diabetic Retinopathy | Retinal Vein Occlusion

Inclusion criteria

• {"criterion_text":"-Must have given written informed consent (signed and dated), and any authorizations required by local law and be able to comply with all study requirements."}
• {"criterion_text":"-Male or female, ≥18 years of age at the time of informed consent."}
• {"criterion_text":"-Females should have no childbearing potential according to Clinical Trial Facilitation Group (CTFG) definition."}
• {"criterion_text":"-Clear ocular media and adequate pupillary dilation in the Study Eye to permit high quality retinal imaging."}
• {"criterion_text":"-Willing to refrain from unusually strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) for at least 72 hours prior to study visits."}
• {"criterion_text":"-DR participants must be diagnosed with mild NPDR (DRSS score of 35) with significant retinal ischemia, or moderately severe or severe NPDR (DRSS score of 47 and 53 respectively), without CI-DMO# that requires immediate treatment*, or mild or moderate PDR without CI-DMO# that requires immediate treatment* defined as having a DRSS score of 61 and 65 respectively. (#DMO not involving the central 1mm subfield will be eligible) (*in the opinion of the Principal Investigator)"}
• {"criterion_text":"-DR participants must be found to have an ETDRS BCVA score in the study eye (SE) of ≥64 ETDRS (equivalent to Snellen 6/15 or 20/50)."}
• {"criterion_text":"-RVO participants must be diagnosed with Retinal Vein Occlusion with onset of symptoms within 28 days prior to first administration of ANXV."}

Exclusion criteria

• {"criterion_text":"-Unwillingness or inability to attend all study visits and/or perform all procedures/tests/examinations, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator."}
• {"criterion_text":"-Treatment with another investigational drug, biological agent, or device within 3 months of Screening Visit, or 5 half-lives of investigational agent, whichever is longer or planned participation in an interventional trial from signing Informed Consent Form (ICF) through Day 120."}
• {"criterion_text":"-History of thromboembolic events or deep venous thrombosis within 3 months of Screening Visit."}
• {"criterion_text":"-Current use of anticoagulant medication (any medications that might have effect on coagulation, haemostasis, and platelets); low dose aspirin allowed prior to informed consent but must be stopped at the time of consent; may begin again 1 day post last study Treatment infusion."}
• {"criterion_text":"-Current daily use of benzodiazepines."}
• {"criterion_text":"-Clinically significant abnormal coagulation parameters at baseline."}
• {"criterion_text":"-History of autoimmune disease with anticipated presence of persistent Annexin A5 antibodies, e.g., antiphospholipid syndrome, systemic lupus erythematosus, rheumatoid arthritis, Behcet disease or systemic sclerosis."}
• {"criterion_text":"-Inherited blood disorder (e.g. sickle cell disease, thalassemia)."}
• {"criterion_text":"-History of unstable coronary artery disease or cerebrovascular accident within the last 3 months."}
• {"criterion_text":"-Current known kidney disease or evidence of kidney disease and eGFR below 60 mL/min/1.73m2 at baseline."}
• {"criterion_text":"-Current drug or alcohol abuse as per the opinion of the Investigator, or current excessive nicotine intake (e.g. ≥ 20 cigarettes/day, or equivalent, as per the opinion of the Investigator)."}
• {"criterion_text":"-Any major (complex, invasive medical or surgical procedure or trauma that carries a higher risk of complications and requires a longer recovery period) medical or surgical procedure or trauma within 4 weeks prior to the day of trial intervention Treatment 1 (ANXV administration), or planned major surgery within the duration of the study through Day 120"}
• {"criterion_text":"-Known history of or positive test for chronic infection that affect the immune system (e.g. hepatitis C (HCV), chronic hepatitis B (HBV) and HIV)."}
• {"criterion_text":"-Class III obesity (Body Mass Index ≥ 40kg/m2), at the time of informed consent (Medical Monitor or Sponsor may accept eligibility for a participant with higher Body Mass Index based on the participant´s overall health status)."}
• {"criterion_text":"-Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol)."}
• {"criterion_text":"-Known hypersensitivity or allergy to fluorescein (e.g., bronchospasm, rash, etc.) or to any component of the study products or a contraindication to dilation of the pupil or fixed pupils; mild allergies without angio-oedema or treatment need may be acceptable if deemed not to be of clinical significance (including but not limited to allergy to animals or mild seasonal hay fever)."}
• {"criterion_text":"-Either or both eyes: A severe (≥0.9 log, Grade 3+ or worse) Relative Afferent Pupillary Defect (RAPD)."}
• {"criterion_text":"-Either or both eyes: An IOP greater than 24 mmHg that is not controlled with medication or surgery at the time of the Screening Visit."}
• {"criterion_text":"-Either or both eyes: Recent (6 months) history of, or presence of uveitis, presence of intraocular inflammation (history of blepharitis is not exclusionary), current ocular infection."}
• {"criterion_text":"-Either or both eyes: Evidence of neovascularization in the study eye (SE) (this exclusion criterion is only applicable for participants with RVO)."}
• {"criterion_text":"-Either or both eyes: ETDRS BCVA score in the Fellow eye of ≤54 (equivalent to Snellen 6/24 or 20/80)."}
• {"criterion_text":"-Either or both eyes: Ocular disorders/additional eye disease, which in the opinion of the Investigator may confound interpretation of study results for the study eye (SE), compromise patient safety, protocol assessments or are likely to require intervention during the study, including, but not limited to, atrophy of the retinal pigment epithelium, sub-retinal fibrosis, organized hard exudate plaque, retinal detachment, macular hole, vitreomacular traction, macular epiretinal membrane, clinically significant cataract, vitreous opacities or haemorrhage, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa or choroidal neovascularization of any cause (e.g., AMD, ocular histoplasmosis, toxoplasmosis, or pathologic myopia) (N.B. If the study eye (SE) is not affected by any of the above mentioned disorders/disease, the participant may be eligible based on Investigator clinical judgement)."}
• {"criterion_text":"-History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant’s ability to participate in the study."}
• {"criterion_text":"-Intravitreal treatment in either eye: - Anti-VEGF treatment within 3 months before Visit 1 (e.g. ranibizumab (Lucentis®), aflibercept (Eylea®), brolucizumab (Beovu®), faricimab (Vabysmo®), bevacizumab (Avastin®) or biosimilar products) - Longer acting anti-VEGF treatment within 6 months before Visit 1 (e.g. 8 mg aflibercept) - Short-acting corticosteroids within 3 months before Visit 1 - Longer-acting corticosteroids within 6 months before Visit 1 (e.g. dexamethasone (Ozurdex®)) - Iluvien® (Flucinolone acetonide intravitreal implant) in the - study eye - within 3 years before Visit 1"}
• {"criterion_text":"-Study Eye only: Evidence of deep intraretinal haemorrhage involving the centre 1mm of the macula."}
• {"criterion_text":"-Study Eye only: Full 4-quadrant panretinal laser photocoagulation with significant retinal carbonisation or RPE loss on UWF-Fundus autofluorescence which, in the opinion of the Principal Investigator, will affect the assessment of the effects of the IMP ANXV"}
• {"criterion_text":"-Study Eye only: Intraocular surgery (including refractive surgery, cataract surgery), or cataract surgery within the preceding 3 months prior to the Screening Visit, or planned intraocular surgery or procedure during the study."}
• {"criterion_text":"-Study Eye only: Recent (6 months) history, or current evidence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus)."}
• {"criterion_text":"-DR participants: CI-DMO (i.e. involving the central 1mm subfield) in study eye which, in the opinion of the Investigator, qualifies for immediate anti-VEGF or laser treatment."}
• {"criterion_text":"-Prior exposure to a recombinant Annexin A5 protein."}
• {"criterion_text":"-History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to biologics (for example systemically administered recombinant proteins/peptides; a similar drug class to ANXV)."}
• {"criterion_text":"-Uncontrolled hypertension (systolic > 180 mmHg or diastolic > 110 mmHg)."}
• {"criterion_text":"-Current use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib) or corticosteroids."}
• {"criterion_text":"-Diagnosed untreated systemic metastasis malignancy."}
• {"criterion_text":"-A current systemic infection or inflammation that may require antiviral or antimicrobial therapy that will not be completed prior to Screening Visit, or that in the opinion of the Investigator and with concurrence of the Medical Monitor may either put the participant at risk or may influence the results of the study, or the participant’s ability to participate in the study."}

Primary endpoints

• {"endpoint_text":"-Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).","definition_or_measurement_approach":""}
• {"endpoint_text":"-Incidence and titre of anti-drug antibodies (ADA) to ANXV pre- and post-administration.","definition_or_measurement_approach":"Measured pre- and post-administration (incidence and titre of ADA)."}

Secondary endpoints

• {"endpoint_text":"-Persistence and titre of ADA.","definition_or_measurement_approach":""}
• {"endpoint_text":"-OCT (CST, Macular Volume and ONL thickness, areas of oedema and DRIL)","definition_or_measurement_approach":"Optical coherence tomography measures: CST, Macular Volume, ONL thickness, areas of oedema and DRIL."}
• {"endpoint_text":"-OCTA (FAZ, VD, Perfusion Density of the Vascular Complex layers on the macula, and vessel skeleton).","definition_or_measurement_approach":"Optical coherence tomography angiography measures: FAZ, vessel density (VD), perfusion density of vascular complex layers, vessel skeleton."}
• {"endpoint_text":"-BCVA (ETDRS letters).","definition_or_measurement_approach":"Best corrected visual acuity measured in ETDRS letters."}
• {"endpoint_text":"-Contrast Sensitivity (letter log contrast sensitivity score).","definition_or_measurement_approach":"Measured as letter log contrast sensitivity score."}
• {"endpoint_text":"-Electroretinogram (ERG) (RETeval: DR Score, amplitude response and implicit time changes from baseline in Flicker ERG, change in PhNR).","definition_or_measurement_approach":"ERG measures (RETeval): DR Score, amplitude response, implicit time changes from baseline in Flicker ERG, change in PhNR."}
• {"endpoint_text":"-Ultra-Wide Field Fundus Fluorescein Angiography (UWF-FFA) (DRSS score, RANP, vessel leakage, conversion from niRVO to iRVO, ISI).","definition_or_measurement_approach":"UWF-FFA measures including DRSS score, RANP, vessel leakage, conversion from non-ischaemic RVO to ischaemic RVO, ISI."}
• {"endpoint_text":"-Ultra-Wide Field Retinal Imaging (resolution of haemorrhages).","definition_or_measurement_approach":"UWF retinal imaging assessing resolution of haemorrhages."}
• {"endpoint_text":"-MMP (changes in Mean Sensitivity).","definition_or_measurement_approach":"Microperimetry (MMP) measuring changes in mean sensitivity."}
• {"endpoint_text":"-Rescue Treatment.","definition_or_measurement_approach":""}
• {"endpoint_text":"-The PK profile of ANXV as determined on the days of Treatment 1, Treatment 4 and Treatment 5 pre-infusion and at 15, 30, and 40 minutes and 1, 1.5, 2 and 4 hours after the start of the infusion.","definition_or_measurement_approach":"Pharmacokinetic sampling schedule: pre-infusion and at 15, 30, 40 minutes and 1, 1.5, 2 and 4 hours after infusion start on specified treatment days."}
• {"endpoint_text":"-PK parameters after the first dose: AUClast, Cmax, Tmax, λz, T½, CL, Vz.","definition_or_measurement_approach":"Standard PK parameters derived from plasma concentration-time data after first dose."}
• {"endpoint_text":"-PK parameters after the first dose: Dose proportionality","definition_or_measurement_approach":""}
• {"endpoint_text":"-PK parameters after the fourth and fifth dose (or third dose for participants only receiving three doses): Area Under the Curve (AUC) during a dosage interval (tau) (AUCtau).","definition_or_measurement_approach":"AUCtau calculated after multiple dosing (4th/5th or 3rd dose for shorter regimens)."}
• {"endpoint_text":"-PK parameters after the fourth and fifth dose (or third dose for participants only receiving three doses): Cmax, Tmax, λz, T½, CL, Vz, Vss.","definition_or_measurement_approach":""}
• {"endpoint_text":"-PK parameters after the fourth and fifth dose (or third dose for participants only receiving three doses): Dose proportionality after multiple doses, based on AUC over the dose interval (AUCtau) and Cmax.","definition_or_measurement_approach":""}
• {"endpoint_text":"-PK parameters after the fourth and fifth dose (or third dose for participants only receiving three doses): Accumulation ratio.","definition_or_measurement_approach":""}
• {"endpoint_text":"-PK parameters after the fourth and fifth dose (or third dose for participants only receiving three doses): Minimum plasma concentrations of ANXV prior to dosing on the day of Treatment 4 and Treatment 5 (Cmin).","definition_or_measurement_approach":""}
• {"endpoint_text":"-PK parameters after the fourth and fifth dose (or third dose for participants only receiving three doses): Mean plasma concentrations of ANXV on the day of Treatment 4 and Treatment 5 (Cmean).","definition_or_measurement_approach":""}

Germany

Earliest CTIS Part Ii Submission Date

23-03-2026

Latest Decision Or Authorization Date

02-04-2026

Processing Time Days

10

Number Of Sites

1

Number Of Participants

12

United Kingdom

Latest Decision Or Authorization Date

02-04-2026

Number Of Participants

6

Primary sponsor

Full Name

Annexin Pharmaceuticals AB (publ)

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Third parties

• {"country":"Norway","full_name":"Smerud Medical Research International AS","duties_or_roles":"[1,5,6,8]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"The Doctors Laboratory Limited","duties_or_roles":"[4]","organisation_type":"Laboratory/Research/Testing facility"}