Non-Proliferative Diabetic RetinopathyPhase 2NEXUSNCT07259928
Safety and Proof of Concept Study of ANXV (Annexin A5) in Patients With Diabetic Retinopathy or Retinal Vein Occlusion
A Phase 2 study testing ANXV in people with Non-Proliferative Diabetic Retinopathy and Retinal Vein Occlusion, run by Annexin Pharmaceuticals AB at 1 site in United Kingdom.
Trial summary
The goal of this clinical trial is to learn about the safety of the investigational medicinal product ANXV. It will also learn about how ANXV works to treat non-proliferative diabetic retinopathy and retinal vein occlusion in adults. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Proliferative Diabetic Retinopathy, Retinal Vein Occlusion
- What is being tested?
- ANXV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 7 Nov 2025to Jul 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible to participate in this trial, an individual must meet all the following criteria:
- 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
- Male or female, ≥18 years of age at the time of informed consent
- Females should have no childbearing potential according to Clinical Trial Facilitation Group (CTFG) definition.
- Clear ocular media and adequate pupillary dilation in the Study Eye to permit high quality retinal imaging
- 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
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- Additionally, NPDR participants must meet the following criteria to be eligible:
- 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
- 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:
- Diagnosed with Retinal Vein Occlusion with onset of symptoms within 28 days prior to first administration of ANXV
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this trial:
- General:
- 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
- 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
- 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
- Prior exposure to a recombinant Annexin A5 protein
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- 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)
- Uncontrolled hypertension (systolic > 180 mmHg or diastolic > 110 mmHg)
- Current use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib) or corticosteroids
- Diagnosed untreated systemic metastasis malignancy
- 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
- 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
- History of thromboembolic events or deep venous thrombosis within 3 months of Screening Visit
- 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
- Current daily use of benzodiazepines
- Clinically significant abnormal coagulation parameters at baseline
- 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
- Inherited blood disorder (e.g. sickle cell disease, thalassemia)
- History of unstable coronary artery disease or cerebrovascular accident within the last 3 months
- Current known kidney disease or evidence of kidney disease and eGFR below 60 mL/min/1.73m2 at baseline
- 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)
- 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)
- Class III obesity (Body Mass Index ≥ 40kg/m2), at the time of informed consent
- 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)
- 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:
- A severe (≥0.9 log, Grade 3+ or worse) Relative Afferent Pupillary Defect (RAPD)
- An IOP greater than 24 mmHg that is not controlled with medication or surgery at the time of the Screening Visit
- Recent (6 months) history of, or presence of uveitis, presence of intraocular inflammation (history of blepharitis is not exclusionary), current ocular infection
- Evidence of neovascularization
- ETDRS BCVA score in the Fellow eye of ≤54 (equivalent to Snellen 6/24 or 20/80)
- 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)
- Receipt within the past 6 months or ongoing intravitreal injection of anti-VEGF treatment in either eye
- Study Eye only:
- Evidence of deep intraretinal haemorrhage involving the centre 1mm of the macula
- Laser photocoagulation in the study eye within the preceding 6 months prior to the Screening Visit, or likely to receive during the study period
- 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
- 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):
- CI-DMO in either eye which, in the opinion of the Investigator, qualifies for anti-VEGF or laser treatment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
The Retina Clinic London
London, W1G9AX
Paulo Eduardo Stanga, +44 20 4548 5310, p.stanga@theretinacliniclondon.com
Sebastian Stanga, +44 20 4548 5310, sebastian@theretinacliniclondon.com
About this study
Official title: 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
The goal of this clinical trial is to learn about the safety of the investigational medicinal product ANXV. It will also learn about how ANXV works to treat non-proliferative diabetic retinopathy and retinal vein occlusion in adults. The main questions it aims to answer are:
- Is ANXV safe to use?
- Does ANXV improve vision or findings related to vision decrease caused by non-proliferative diabetic retinopathy or retinal vein occlusion?
- Does ANXV lower the number of times participants need to use a rescue medication? Researchers will compare different dose levels of ANXV to see what dose would be be appropriate to test in larger studies.
Read more
Participants will:
Take ANXV as a 30 minutes infusion (slow injection) for 5 days. Visit the clinic for checkups and tests at 11 visits during 4 months.
Read the detailed description
The study is an open label, prospective, dose evaluation study to investigate the safety, tolerability and efficacy in patients with Non-Proliferative Diabetic Retinopathy (NPDR) or Retinal Rein Occlusion with recent onset (within 28 days from symptoms onset or diagnosis (whichever is first) to first treatment).
The study consists of 11 visits, whereof one screening visit, five treatment visits and five follow up visits, during a 4 months period.
Intervention is intravenous infusion (30 minutes) with the investigational medicinal product ANXV, a recombinant Annexin A5 protein. The intended dose levels are 4 mg, 1 mg and 6 mg, daily administration for five days.
Safety will be regularly evaluated by the Medical Monitors on a per need basis, as data become available. In case of safety concerns within one indication subset (NPDR and RVO), a lower dose will be initiated within the concerned indication subset (for each subset, independently).
The following assessments will be performed:
Ocular assessments:
- BCVA
- OCT and OCTA
- ERG
- UWF-retinal imaging
- UWF-FFA
- Ocular examination - Slit Lamp biomicroscopy examination, Intraocular Pressure (IOP), RAPD
- Dilated indirect ophthalmoscopy
Non-ocular assessments:
- Vital signs
- ECG
- Safety labs (blood and urine)
- Study labs (blood)
- Being tested
- ANXV
- Keywords
- Annexin A5, ANXV, Retinal Vein Occlusion, Non-Profilerative Diabetic Retinopathy, RVO, NPDR
- Medical subject headings
- Retinal Vein Occlusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ANXVBiological
Human Recombinant Protein Annexin A5
| Study group | Role | What they receive |
|---|---|---|
| NPDR, 4mg, 5 doses | Experimental | ANXV 4mg 30 min infusion Receives: Biological: ANXV |
| RVO, 4mg, 5 doses | Experimental | ANXV 4mg 30 min infusion Receives: Biological: ANXV |
| NPDR, 6 mg, 5 doses | Experimental | ANXV 6mg 30 min infusion Receives: Biological: ANXV |
| RVO, 4 mg, 3 doses | Experimental | ANXV 4mg 30 min infusion Receives: Biological: ANXV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
- Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
- Incidence and titre of anti-drug antibodies (ADA) to ANXV pre- and post-administration
Measured: From day 1 to day 120
Secondary outcomes (4)
Anti-drug antibody
Presence of anti-drug antibodies to ANXV
Measured: From day 1 to day 120
Proof of concept
Efficacy measured by eye functional and anatomical assessments.
Measured: From day 1 to day 120
ANXV concentration
ANXV concentration in blood and urine
Measured: From start of administration up to four hours after start of administration, during all treatment days
Rescue medication use
Number of rescue medication occasions
Measured: From day 1 to day 120
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2025
- Study start7 Nov 2025
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Proliferative Diabetic RetinopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Annexin Pharmaceuticals AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anna Frostegård, MD, PhD, Study director, Annexin Pharmaceuticals AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07259928
- Sponsor's protocol ID
- ANN-008
- Other IDs
- 1012020
- Acronym
- NEXUS
- Status last verified
- Nov 2025
- First submitted
- 16 Sep 2025
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD used in a results publication
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07259928
- Acronym / sponsor ID
- NEXUS / ANN-008
- Keywords
- Annexin A5, ANXV, Retinal Vein Occlusion, Non-Profilerative Diabetic Retinopathy, RVO, NPDR
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Annexin Pharmaceuticals ABIndustry (pharma, biotech, devices)
- Study start
- 7 Nov 2025 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 2 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn about the safety of the investigational medicinal product ANXV. It will also learn about how ANXV works to treat non-proliferative diabetic retinopathy and retinal vein occlusion in adults. The main questions it aims to answer are:
- Is ANXV safe to use?
- Does ANXV improve vision or findings related to vision decrease caused by non-proliferative diabetic retinopathy or retinal vein occlusion?
- Does ANXV lower the number of times participants need to use a rescue medication? Researchers will compare different dose levels of ANXV to see what dose would be be appropriate to test in larger studies.
Participants will:
Take ANXV as a 30 minutes infusion (slow injection) for 5 days. Visit the clinic for checkups and tests at 11 visits during 4 months.
Detailed description
The study is an open label, prospective, dose evaluation study to investigate the safety, tolerability and efficacy in patients with Non-Proliferative Diabetic Retinopathy (NPDR) or Retinal Rein Occlusion with recent onset (within 28 days from symptoms onset or diagnosis (whichever is first) to first treatment).
The study consists of 11 visits, whereof one screening visit, five treatment visits and five follow up visits, during a 4 months period.
Intervention is intravenous infusion (30 minutes) with the investigational medicinal product ANXV, a recombinant Annexin A5 protein. The intended dose levels are 4 mg, 1 mg and 6 mg, daily administration for five days.
Safety will be regularly evaluated by the Medical Monitors on a per need basis, as data become available. In case of safety concerns within one indication subset (NPDR and RVO), a lower dose will be initiated within the concerned indication subset (for each subset, independently).
The following assessments will be performed:
Ocular assessments:
- BCVA
- OCT and OCTA
- ERG
- UWF-retinal imaging
- UWF-FFA
- Ocular examination - Slit Lamp biomicroscopy examination, Intraocular Pressure (IOP), RAPD
- Dilated indirect ophthalmoscopy
Non-ocular assessments:
- Vital signs
- ECG
- Safety labs (blood and urine)
- Study labs (blood)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NPDR, 4mg, 5 doses | Experimental | Biological: ANXVANXV 4mg 30 min infusion |
| RVO, 4mg, 5 doses | Experimental | Biological: ANXVANXV 4mg 30 min infusion |
| NPDR, 6 mg, 5 doses | Experimental | Biological: ANXVANXV 6mg 30 min infusion |
| RVO, 4 mg, 3 doses | Experimental | Biological: ANXVANXV 4mg 30 min infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- To be eligible to participate in this trial, an individual must meet all the following criteria:
- 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
- Male or female, ≥18 years of age at the time of informed consent
- Females should have no childbearing potential according to Clinical Trial Facilitation Group (CTFG) definition.
- Clear ocular media and adequate pupillary dilation in the Study Eye to permit high quality retinal imaging
Key exclusion criteria (40 listed)
- An individual who meets any of the following criteria will be excluded from participation in this trial:
- 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
- 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
- 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
- Prior exposure to a recombinant Annexin A5 protein
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ANXVHuman Recombinant Protein Annexin A5 | Biological | NPDR, 4mg, 5 doses, NPDR, 6 mg, 5 doses, RVO, 4 mg, 3 doses, RVO, 4mg, 5 doses |
Primary outcome
Safety and tolerability
Time frame: From day 1 to day 120
* Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) * Incidence and titre of anti-drug antibodies (ADA) to ANXV pre- and post-administration
4 secondary outcomes
Anti-drug antibody
Time frame: From day 1 to day 120
Proof of concept
Time frame: From day 1 to day 120
ANXV concentration
Time frame: From start of administration up to four hours after start of administration, during all treatment days
Rescue medication use
Time frame: From day 1 to day 120
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Individual participant dataSharing planned: Yes. IPD used in a results publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anna Frostegård, MD, PhD study director
Annexin Pharmaceuticals AB
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ANXV in people with Non-Proliferative Diabetic Retinopathy and Retinal Vein Occlusion, run by Annexin Pharmaceuticals AB at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna Frostegård (+46701104258, anna.frostegard@annexinpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability (time frame: From day 1 to day 120). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.