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Retinal Vein OcclusionPhase 2NCT05532735

Safety and Proof of Concept Study of ANXV (Annexin A5) in Patients With Retinal Vein Occlusion

A Phase 2 study testing ANXV in people with Retinal Vein Occlusion, run by Annexin Pharmaceuticals AB at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Open-label, dose ascending safety, tolerability, and proof of concept study to evaluate the use of ANXV (human recombinant Annexin A5) in the treatment of subjects with recently diagnosed Retinal Vein Occlusion. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
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
16 participants
Where
7 sitesUnited States
Study dates
24 Aug 2022to 11 Nov 2024
Phase
Phase 2
Are there results?
None posted in the registry

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

  • 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 must be non-pregnant and non-lactating, and either surgically sterile (e.g., ≥6 weeks post bilateral salpingectomy, bilateral oophorectomy with or without hysterectomy) or post-menopausal (12 months of spontaneous amenorrhea in females > 55years of age or, in females ≤55 years, or 12 months of spontaneous amenorrhea without an alternative medical, or 12 months with an elevated Follicle Stimulating Hormone (FSH) level Males must either be surgically sterile or abstinent*, or if engaged in sexual relations with a female of child-bearing potential, the subject or the subject's non-pregnant female partner must use a highly effective contraception method from the time of signing the Informed Consent Form (ICF) until at least 30 days after the last dose of study drug; Refer to Section 10.3 for acceptable methods
  • Abstinence is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods). Declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception (Section 10.3).
  • Onset of symptoms of Retinal Vein Occlusion within 23 days prior to informed consent
  • The criterion has been removed
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  • The criterion has been removed
  • Clear ocular media and adequate pupillary dilation in the Study Eye to permit high quality retinal imaging
  • Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) for at least 72 hours prior to study visits
  • A negative rapid SARS-CoV-2 (COVID) test on Day 1 prior to initiation of study drug infusion

Who cannot join

  • Subjects will not be eligible if they have any of the following criteria:
  • Study Eye only:
  • A severe (≥0.9 log, Grade 3+ or worse) Relative Afferent Pupillary Defect (RAPD)
  • Evidence of deep intraretinal hemorrhage involving the center 1mm of the macula
  • Evidence of neovascularization
  • 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, clinically significant diabetic macular edema, retinal detachment, macular hole, vitreomacular traction, macular epiretinal membrane, clinically significant cataract, vitreal opacities or hemorrhage, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa or choroidal neovascularization of any cause (e.g., Age-related Macular Degeneration (AMD), ocular histoplasmosis, toxoplasmosis, or pathologic myopia)
Show all 39Show fewer
  • Laser photocoagulation in the study eye within the preceding 6 months prior to the Screening Visit
  • Receipt within the past 6 months prior to the Screening Visit of any intraocular surgery (including refractive surgery, cataract surgery), or intravitreal (IVT) injection, or planned intraocular surgery or procedure during the study, unless approved by Medical Monitor or Sponsor
  • Recent (6 months) history, or current evidence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus), unless approved by Medical Monitor or Sponsor
  • Fellow Eye:
  • BCVA in the Fellow eye of ≤70 ETDRS letters (approximately 20/40 or less), unless approved by the Medical Monitor or the Sponsor
  • Both Eyes:
  • Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens, or optic nerve (e.g., desferoxamine, 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-edema 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)
  • 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
  • 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 medical or surgical procedure or trauma within 4 weeks prior to the day of Treatment 1 (study drug administration), or planned major surgery within the duration of the study through Day 120, unless approved by Medical Monitor or Sponsor
  • History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
  • Prior exposure to a recombinant Annexin A5
  • 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, approved or 5 half-lives of investigational agent
  • 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 subject at risk or may influence the results of the study, or the subject'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 investigational trial from signing 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, hemostasis, 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 (intermittent use permissible with Medical Monitor or Sponsor approval)
  • Clinically significant abnormal coagulation parameters at baseline
  • The criterion has been removed from the protocol
  • 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
  • GFR below 70 mL/min at baseline
  • Current drug or alcohol abuse, current excessive smoking (i.e., ≥ 20/day)
  • Known history of or positive test for hepatitis C or chronic hepatitis B
  • Class III obesity (Body Mass Index ≥ 40kg/m2), at the time of informed consent (Sponsor may accept eligibility for a subject with higher Body Mass Index

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Retina Consultants of Texas

    Bellaire, Texas, 77401

  • Cumberland Valley Retina Consultants

    Hagerstown, Maryland, 21740

  • Valley Retina Institute

    McAllen, Texas, 78503

  • Retina Consultants of Texas

    San Antonio, Texas, 78240

  • Tulsa Retina Consultants

    Tulsa, Oklahoma, 74114

  • Virginia Retina Center

    Warrenton, Virginia, 20186

  • Eye Associates of Northeast Louisiana

    West Monroe, Louisiana, 71219

Other trials in United States

About this study

Official title: Open-label, Dose Ascending Safety, Tolerability, and Proof of Concept Study to Evaluate the Use of ANXV (Human Recombinant Annexin A5) in the Treatment of Subjects With Recently Diagnosed Retinal Vein Occlusion

Open-label, dose ascending safety, tolerability, and proof of concept study to evaluate the use of ANXV (human recombinant Annexin A5) in the treatment of subjects with recently diagnosed Retinal Vein Occlusion.

Being tested
ANXV
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

    ANXV (Human recombinant Annexin A5 protein)

Study groups in NCT05532735
Study groupRoleWhat they receive
2 mg ANXVExperimentalANXV (human recombinant Annexin A5), infusion, 2 mg daily during five days.
Receives: Biological: ANXV
4 mg ANXVExperimentalANXV (human recombinant Annexin A5), infusion, 4 mg daily during five days.
Receives: Biological: ANXV
1 mg ANXVExperimentalANXV (human recombinant Annexin A5), infusion, 1 mg daily during five days.
Receives: Biological: ANXV
6 mg ANXVExperimentalANXV (human recombinant Annexin A5), infusion, 6 mg daily during five days.
Receives: Biological: ANXV
8 mg ANXVExperimentalANXV (human recombinant Annexin A5), infusion, 8 mg daily during five days.
Receives: Biological: ANXV

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety - Treatment Emergent Adverse Events

    Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Measured: 120 days

  2. Safety - Anti-drug antibodies

    Incidence and titer of anti-drug antibodies (ADA) to ANXV pre- and post-administration

    Measured: 120 days

Secondary outcomes (28)

  1. Safety - Slit lamp

    Slit-lamp biomicroscopy including intraocular pressure (IOP) and dilated indirect ophthalmoscopy

    Measured: 120 days

  2. Safety - Gonioscopy

    Measured: 120 days

  3. Safety - Best Corrected Visual Acuity (BCVA)

    Distance BCVA by manifest refraction should be performed utilizing the ETDRS chart at a starting distance of 4 meters

    Measured: 120 days

  4. Safety - laboratory parameters

    Concentration of analytes in Chemistry panel, lipid panel, hematology, coagulation, inflammatory and urinalysis

    Measured: 15 days

  5. Safety - vital signs Blood Pressure

    Blood pressure (BP)

    Measured: 15 days

  6. Safety - vital signs Heart rate

    Heart rate (HR)

    Measured: 15 days

  7. Safety - vital signs Weight

    Weight

    Measured: 15 days

  8. Safety - vital signs Body Temperature

    Body temperature

    Measured: 15 days

  9. Safety - vital signs Respiratory rate

    Respiratory rate (RR)

    Measured: 15 days

  10. Safety - vital signs Pulse oximetry

    Pulse oximetry

    Measured: 15 days

  11. Safety - ECG

    12-lead ECG

    Measured: 15 days

  12. Safety - ANXV anti-drug antibodies Persistence

    Persistence anti-drug antibodies

    Measured: 12 months

  13. Safety - ANXV anti-drug antibodies Titer

    Titer of anti-drug antibodies

    Measured: 12 months

  14. Efficacy - Microperimetry Change from baseline

    Change from baseline in microperimetry mean retinal sensitivity calculated on all stimulus points ≤20 dB at baseline (MSEff), at Days 8, 15, and 29

    Measured: 120 days

  15. Efficacy - Microperimetry Stimulus points

    Number of microperimetry stimulus points that improve by ≥7decibels (dB) from baseline to Day 8 and 29 after the first ANXV infusion

    Measured: 120 days

  16. Efficacy - Microperimetry Improvement over baseline

    Number of subjects with an improvement over baseline in MSEff of ≥7dB at Days 8, 15 and 29 (MMP positive responders, MMP-pos)

    Measured: 120 days

  17. Efficacy - Microperimetry Incremental loss

    Number of subjects with an incremental loss over baseline in MSEff of ≥7dB at Days 8, 15 and 29 (MMP negative responders, MMP-neg)

    Measured: 120 days

  18. Efficacy - Microperimetry Improvement of ≥7dB

    Number of subjects with an improvement of ≥7dB over baseline in ≥5 stimulus points at Days 8, 15 and 29 (MMP positive-5 responders, MMP-pos-5)

    Measured: 120 days

  19. Efficacy - Microperimetry MMP negative-5 responders

    Number of MMP negative-5 responders, i.e., subjects with an incremental loss over baseline of ≥7dB in ≥5 stimulus points at Days 8, 15 and 29 (MMP-neg-5)

    Measured: 120 days

  20. Efficacy - BCVA Improvement

    Number of subjects with an improvement of ≥15 ETDRS letters over baseline at Days 8, 15 and 29

    Measured: 120 days

  21. Efficacy - BCVA Improvement or letter score ≥78

    Number of subjects with an improvement of ≥15 ETDRS letters over baseline or an ETDRS letters score ≥78 at Days 8, 15 and 29

    Measured: 120 days

  22. Efficacy - Spectral Domain Optical Coherence Tomography / Spectral Domain Optical Coherence Tomography Angiography (SD-OCT/OCTA) SD-OCT

    Change from baseline in Center Subfield Macular Thickness (CMT), Macular Volume and Outer Nuclear Layer (ONL) thickness on SD-OCT at Days 8, 15 and 29

    Measured: 120 days

  23. Efficacy - Spectral Domain Optical Coherence Tomography / Spectral Domain Optical Coherence Tomography Angiography (SD-OCT/OCTA) OCTA

    Change from baseline in Foveal Avascular Zone (FAZ) and Vessel Density (VD) on OCTA at Days 8, 15 and 29

    Measured: 120 days

  24. Efficacy - Ultra-Wide Field Fluorescein Angiography (UWF-FA) Size of Retinal Area of Non-Perfusion

    Change from baseline at Days 8 and 29 in the size of Retinal Area of Non-Perfusion (RANP) for:

    1. all the retina captured by UWF-FA
    2. in posterior pole

    Measured: 120 days

  25. Efficacy - Ultra-Wide Field Fluorescein Angiography (UWF-FA) Conversion from non-ischemic RVO to ischemic RVO

    Number of subjects at Days 8, and 29 with:

    1. RANP ≥30 DA
    2. RANP ≥10 DA Rate of conversion from non-ischemic RVO (niRVO) to ischemic RVO (iRVO) by Day 29

    Measured: 120 days

  26. Efficacy - Need for rescue treatment with anti Vascular Endothelial Growth Factor (aVEGF) therapy

    Number of subjects requiring rescue with an aVEGF by Day 29

    Measured: 29 days

  27. Ischemic Index

    Change in Ischemic Index (ISI) from baseline at Days 8 and 29

    Measured: 120 Days

  28. Pharmacokinetic (PK) profile

    ANXV concentration on Days 1 and 5 pre-infusion and at 15, 30, and 40 minutes and 1, 1.5, 2 and 3.5 hours after the start of the infusion

    Measured: 5 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2022
  2. Study start24 Aug 2022
  3. Primary completion17 Jul 2024
  4. Study completion11 Nov 2024

Resources

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
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05532735
Sponsor's protocol ID
ANN-004
Status last verified
Oct 2024
First submitted
18 Jul 2022
Last updated
11 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ANXV in people with Retinal Vein Occlusion, run by Annexin Pharmaceuticals AB at 7 sites in United States.

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 10 inclusion and 39 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: finished, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety - Treatment Emergent Adverse Events (time frame: 120 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05532735.

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 11 Dec 2024.

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