ANXV (Annexin A5) infusions for non-proliferative diabetic retinopathy and retinal vein occlusion

Open-label, Safety, Tolerability and Proof of Concept Study to Evaluate the Use of ANXV (Recombinant Human Annexin A5 Protein) in the Treatment of Patients With Either Diabetic Retinopathy or Recent Onset Retinal Vein Occlusion

This will test whether short daily infusions of ANXV can be given safely and help improve vision or reduce the need for rescue medication in adults with recent-onset non-proliferative diabetic retinopathy or retinal vein occlusion.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Annexin Pharmaceuticals AB (Industry-sponsored)
• Drugs / interventions: bevacizumab, cetuximab, sunitinib
• Locations: 1 site (London)
• Trial ID: NCT07259928 on ClinicalTrials.gov

What this trial studies

This open-label, phase 2 dose-ranging study gives adults with moderately severe or severe non‑proliferative diabetic retinopathy (DRSS 47 or 53) or recent-onset retinal vein occlusion daily 30-minute intravenous infusions of recombinant Annexin A5 (ANXV) for five days. Participants attend 11 clinic visits over four months for visual acuity and retinal imaging (BCVA, OCT/OCTA, ERG, UWF imaging and FFA) plus safety monitoring including labs, ECG and vital signs. Planned dose levels (1 mg, 4 mg and 6 mg) are compared to identify a tolerable dose and collect early signals on vision and the need for rescue treatment. Safety reviews will be performed continuously with the option to alter dosing independently within each indication subgroup if concerns arise.

Who should consider this trial

Good fit: Adults aged 18 or older with clear ocular media and either moderately severe or severe non‑proliferative diabetic retinopathy (DRSS 47 or 53) or retinal vein occlusion with symptom onset or diagnosis within 28 days are the intended participants.

Not a fit: Patients with proliferative diabetic retinopathy, chronic or long‑standing retinal vein occlusion, clinically important diabetic macular oedema, or other significant ocular comorbidities are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If ANXV is effective and safe, it could reduce vision loss and lower how often patients need rescue treatments for these retinal vascular conditions.

How similar studies have performed: ANXV is a novel therapeutic approach with limited prior clinical data in these retinal diseases, while established treatments such as anti‑VEGF injections work by different mechanisms.

Eligibility criteria

Inclusion Criteria:

To be eligible to participate in this trial, an individual must meet all the following criteria:

1. 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
2. Male or female, ≥18 years of age at the time of informed consent
3. Females should have no childbearing potential according to Clinical Trial Facilitation Group (CTFG) definition.
4. Clear ocular media and adequate pupillary dilation in the Study Eye to permit high quality retinal imaging
5. 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

   Additionally, NPDR participants must meet the following criteria to be eligible:
6. Diagnosed with moderately severe or severe non-proliferative Diabetic Retinopathy defined as having a DRSS score of 47 and 53 respectively, and no CI-DMO
7. Found to have an ETDRS BCVA score in the study eye (SE) of ≥69 ETDRS (equivalent to Snellen 6/12 or 20/40)

   Additionally, RVO participants must meet the following criteria to be eligible:
8. Diagnosed with Retinal Vein Occlusion with onset of symptoms within 28 days prior to first administration of ANXV

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this trial:

General:

1. 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
2. Any major 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
3. 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
4. Prior exposure to a recombinant Annexin A5 protein
5. 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)
6. Uncontrolled hypertension (systolic \> 180 mmHg or diastolic \> 110 mmHg)
7. Current use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib) or corticosteroids
8. Diagnosed untreated systemic metastasis malignancy
9. 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
10. 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
11. History of thromboembolic events or deep venous thrombosis within 3 months of Screening Visit
12. 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 Treatment 5 infusion
13. Current daily use of benzodiazepines
14. Clinically significant abnormal coagulation parameters at baseline
15. 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
16. Inherited blood disorder (e.g. sickle cell disease, thalassemia)
17. History of unstable coronary artery disease or cerebrovascular accident within the last 3 months
18. Current known kidney disease or evidence of kidney disease and eGFR below 60 mL/min/1.73m2 at baseline
19. 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)
20. 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)
21. Class III obesity (Body Mass Index ≥ 40kg/m2), at the time of informed consent
22. 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/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol)
23. 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)

    Either or both eyes:
24. A severe (≥0.9 log, Grade 3+ or worse) Relative Afferent Pupillary Defect (RAPD)
25. An IOP greater than 24 mmHg that is not controlled with medication or surgery at the time of the Screening Visit
26. Recent (6 months) history of, or presence of uveitis, presence of intraocular inflammation (history of blepharitis is not exclusionary), current ocular infection
27. Evidence of neovascularization
28. ETDRS BCVA score in the Fellow eye of ≤54 (equivalent to Snellen 6/24 or 20/80)
29. Ocular disorders/additional eye disease, which in the opinion of the Investigator may confound interpretation of study results, compromise 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)
30. Receipt within the past 6 months or ongoing intravitreal injection of anti-VEGF treatment in either eye

    Study Eye only:
31. Evidence of deep intraretinal haemorrhage involving the centre 1mm of the macula
32. Laser photocoagulation in the study eye within the preceding 6 months prior to the Screening Visit, or likely to receive during the study period
33. Intraocular surgery (including refractive surgery, cataract surgery), or intravitreal (IVT) injection within the preceding 6 months prior to the Screening Visit, or cataract surgery within the preceding 3 months prior to the Screening Visit, or planned intraocular surgery or procedure during the study
34. Recent (6 months) history, or current evidence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus)

    NPDR participants will not be eligible if they meet any of the following criteria (only NPDR participants):
35. CI-DMO in either eye which, in the opinion of the Investigator, qualifies for anti-VEGF or laser treatment

Where this trial is running

London

• The Retina Clinic London — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Anna Frostegård

Conditions Non-Proliferative Diabetic Retinopathy; Retinal Vein Occlusion; Annexin A5; ANXV; Non-Profilerative Diabetic Retinopathy; RVO; NPDR