Clinical trial NCT05532735: Safety and Proof of Concept Study of ANXV (Annexin A5) in Patients With Retinal Vein Occlusion
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Retinal Vein Occlusion
Lead sponsor: Annexin Pharmaceuticals AB
Sponsor class: INDUSTRY
Collaborators: name: InFocus Clinical Research
First posted: 2022-09-08
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion 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 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).
4. Onset of symptoms of Retinal Vein Occlusion within 23 days prior to informed consent
5. The criterion has been removed
6. The criterion has been removed
7. Clear ocular media and adequate pupillary dilation in the Study Eye to permit high quality retinal imaging
8. 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
9. A negative rapid SARS-CoV-2 (COVID) test on Day 1 prior to initiation of study drug infusion

Exclusion Criteria:

Subjects will not be eligible if they have any of the following criteria:

Study Eye only:

1. A severe (≥0.9 log, Grade 3+ or worse) Relative Afferent Pupillary Defect (RAPD)
2. Evidence of deep intraretinal hemorrhage involving the center 1mm of the macula
3. Evidence of neovascularization
4. 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)
5. Laser photocoagulation in the study eye within the preceding 6 months prior to the Screening Visit
6. 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
7. 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:
8. 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:
9. 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)
10. 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)
11. An IOP greater than 24 mmHg that is not controlled with medication or surgery at the time of the Screening Visit
12. Recent (6 months) history of, or presence of uveitis, presence of intraocular inflammation (history of blepharitis is not exclusionary), current ocular infection

    General:
13. 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
14. 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
15. 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
16. Prior exposure to a recombinant Annexin A5
17. 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)
18. Uncontrolled hypertension (systolic \> 180 mmHg or diastolic \> 110 mmHg)
19. 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
20. Diagnosed untreated systemic metastasis malignancy
21. 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
22. 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
23. History of thromboembolic events or deep venous thrombosis within 3 months of Screening Visit
24. 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
25. Current daily use of benzodiazepines (intermittent use permissible with Medical Monitor or Sponsor approval)
26. Clinically significant abnormal coagulation parameters at baseline
27. The criterion has been removed from the protocol
28. 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
29. Inherited blood disorder (e.g. sickle cell disease, thalassemia)
30. History of unstable coronary artery disease or cerebrovascular accident within the last 3 months
31. GFR below 70 mL/min at baseline
32. Current drug or alcohol abuse, current excessive smoking (i.e., ≥ 20/day)
33. Known history of or positive test for hepatitis C or chronic hepatitis B
34. 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

Primary outcomes:
measure: Safety - Treatment Emergent Adverse Events
timeFrame: 120 days
measure: Safety - Anti-drug antibodies
timeFrame: 120 days
Secondary outcomes:
measure: Safety - Slit lamp
timeFrame: 120 days
measure: Safety - Gonioscopy
timeFrame: 120 days
measure: Safety - Best Corrected Visual Acuity (BCVA)
timeFrame: 120 days
measure: Safety - laboratory parameters
timeFrame: 15 days
measure: Safety - vital signs Blood Pressure
timeFrame: 15 days
measure: Safety - vital signs Heart rate
timeFrame: 15 days
measure: Safety - vital signs Weight
timeFrame: 15 days
measure: Safety - vital signs Body Temperature
timeFrame: 15 days
measure: Safety - vital signs Respiratory rate
timeFrame: 15 days
measure: Safety - vital signs Pulse oximetry
timeFrame: 15 days
measure: Safety - ECG
timeFrame: 15 days
measure: Safety - ANXV anti-drug antibodies Persistence
timeFrame: 12 months
measure: Safety - ANXV anti-drug antibodies Titer
timeFrame: 12 months
measure: Efficacy - Microperimetry Change from baseline
timeFrame: 120 days
measure: Efficacy - Microperimetry Stimulus points
timeFrame: 120 days
measure: Efficacy - Microperimetry Improvement over baseline
timeFrame: 120 days
measure: Efficacy - Microperimetry Incremental loss
timeFrame: 120 days
measure: Efficacy - Microperimetry Improvement of ≥7dB
timeFrame: 120 days
measure: Efficacy - Microperimetry MMP negative-5 responders
timeFrame: 120 days
measure: Efficacy - BCVA Improvement
timeFrame: 120 days
measure: Efficacy - BCVA Improvement or letter score ≥78
timeFrame: 120 days
measure: Efficacy - Spectral Domain Optical Coherence Tomography / Spectral Domain Optical Coherence Tomography Angiography (SD-OCT/OCTA) SD-OCT
timeFrame: 120 days
measure: Efficacy - Spectral Domain Optical Coherence Tomography / Spectral Domain Optical Coherence Tomography Angiography (SD-OCT/OCTA) OCTA
timeFrame: 120 days
measure: Efficacy - Ultra-Wide Field Fluorescein Angiography (UWF-FA) Size of Retinal Area of Non-Perfusion
timeFrame: 120 days
measure: Efficacy - Ultra-Wide Field Fluorescein Angiography (UWF-FA) Conversion from non-ischemic RVO to ischemic RVO
timeFrame: 120 days
measure: Efficacy - Need for rescue treatment with anti Vascular Endothelial Growth Factor (aVEGF) therapy
timeFrame: 29 days
measure: Ischemic Index
timeFrame: 120 Days
measure: Pharmacokinetic (PK) profile
timeFrame: 5 days
Other outcomes:
measure: ANXV binding sites
timeFrame: 43 days
measure: Endogenous Annexin A5
timeFrame: 43 days
Locations:
city: West Monroe
country: United States
facility: Eye Associates of Northeast Louisiana
state: Louisiana
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Tulsa
country: United States
facility: Tulsa Retina Consultants
state: Oklahoma
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute
state: Texas
city: San Antonio
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Warrenton
country: United States
facility: Virginia Retina Center
state: Virginia
Study officials:
affiliation: Annexin Pharmaceuticals
name: Anna Frostegård
role: STUDY_DIRECTOR
References: