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

Korábbi kezelés

• 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
• Prior exposure to a recombinant Annexin A5 protein
• Current use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib) or corticosteroids
• 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
• 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)
• 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)
• An IOP greater than 24 mmHg that is not controlled with medication or surgery at the time of the Screening Visit
• 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

Más betegség

• 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
• 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)
• Diagnosed untreated systemic metastasis malignancy
• History of thromboembolic events or deep venous thrombosis within 3 months of Screening Visit
• 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
• 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)
• 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:
• Recent (6 months) history of, or presence of uveitis, presence of intraocular inflammation (history of blepharitis is not exclusionary), current ocular infection
• 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)
• Evidence of deep intraretinal haemorrhage involving the centre 1mm of the macula
• 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):

Laborértékek

• 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 known kidney disease or evidence of kidney disease and eGFR below 60 mL/min/1.73m2 at baseline

Egyéb

• 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
• Current daily use of benzodiazepines
• Clinically significant abnormal coagulation parameters at baseline
• Class III obesity (Body Mass Index ≥ 40kg/m2), at the time of informed consent
• A severe (≥0.9 log, Grade 3+ or worse) Relative Afferent Pupillary Defect (RAPD)
• Evidence of neovascularization
• ETDRS BCVA score in the Fellow eye of ≤54 (equivalent to Snellen 6/24 or 20/80)
• Receipt within the past 6 months or ongoing intravitreal injection of anti-VEGF treatment in either eye
  • Study Eye only:
• CI-DMO in either eye which, in the opinion of the Investigator, qualifies for anti-VEGF or laser treatment

• 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
  • 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