Near-Infrared Fluorescence Molecular Imaging of ANXV-800CW to Visualize its Biodistribution in the Eyes of Patients Suffering from Retinal Vein Occlusion and Diabetic Retinopathy

RVO:
- Willing to adhere to the prohibitions and restrictions specified in this
protocol.
- Capable of giving signed informed consent (voluntarily), indicating that the
patient understands the purpose and procedures required for the study and is
willing to comply with the requirements and restrictions listed in the informed
consent form and in this protocol.
- Patients aged 18-85 years inclusive at moment signing informed consent form.
- Established (sub) acute Retinal Vein Occlusion
o Branch retinal vein occlusion (BRVO) or Central retinal vein occlusion (CRVO)
- BMI >= 18.0 and <= 35.0 kg/m2
- Overtly healthy based on medical history, physical findings, vital signs, ECG
at the time of screening, as judged by the Investigator.
o Note: one retest of vital functions and ECG is allowed within the screening
window
- No clinically significant laboratory abnormalities as determined by the
investigator
o Note: one retest of lab tests is allowed within the screening window
- Female patients should fulfil one of the following criteria:
o At least 1 year post-menopausal (amenorrhea >12 months and/or
follicle-stimulating hormone >30 mIU/mL) at screening;
o Surgically sterile (bilateral oophorectomy, hysterectomy, or tubal ligation);
o Women >45 years of age without a child wish, who agree to use an adequate
form of contraceptives during the study and whom have not the intention to
become pregnant anymore. In the case of an unlikely pregnancy, they accept the
possible maternal/ fetal risk of participation in the study
- Male subjects who are sexually active with a female partner of childbearing
potential must agree to the use of an effective method of birth control, and
must not donate sperm, until 3 months after administration of ANXV-800CW.

DR:
- Willing to adhere to the prohibitions and restrictions specified in this
protocol.
- Capable of giving signed informed consent (voluntarily), indicating that the
patient understands the purpose and procedures required for the study and is
willing to comply with the requirements and restrictions listed in the informed
consent form and in this protocol.
- Patients aged 18-85 years inclusive at moment signing informed consent form.
- Patients should be graded as one of the following:
o Diabetic retinopathy grade R2 pre-proliferative
o Diabetic retinopathy grade R3 proliferative
o Diabetic maculopathy grade M1
- BMI >= 18.0 and <= 35.0 kg/m2
- Overtly healthy based on medical history, physical findings, vital signs, ECG
at the time of screening, as judged by the Investigator.
o Note: one retest of vital functions and ECG is allowed within the screening
window
- No clinically significant laboratory abnormalities as determined by the
investigator
o Note: one retest of lab tests is allowed within the screening window
- Female patients should fulfil one of the following criteria:
o At least 1 year post-menopausal (amenorrhea >12 months and/or
follicle-stimulating hormone >30 mIU/mL) at screening;
o Surgically sterile (bilateral oophorectomy, hysterectomy, or tubal ligation);
o Women >45 years of age without a child wish, who agree to use an adequate
form of contraceptives during the study and whom have not the intention to
become pregnant anymore. In the case of an unlikely pregnancy, they accept the
possible maternal/ fetal risk of participation in the study
- Male subjects who are sexually active with a female partner of childbearing
potential must agree to the use of an effective method of birth control, and
must not donate sperm, until 3 months after administration of ANXV-800CW.

RVO:
General:
- Behavioral or cognitive impairment or psychiatric disease that in the opinion
of the investigator affects the ability of the patient to understand and
cooperate with the study protocol
- Deprived of freedom by an administrative or court order or in an emergency
setting.
- Insufficient venous access for the study procedures.
- Close affiliation with the investigator; e.g. a close relative of the
investigator,
dependent person (e.g. employee or student), employee of the department of
Ophthalmology of the UMCG, TRACER or affiliates
- Any finding in the medical examinations or medical history giving, in the
opinion of the Investigator, reasonable suspicion of a disease or condition
that makes treatment with the investigational drug unadvisable, or that might
affect interpretation of the results of the study or render the patient at high
risk for treatment complications
- Participation in an interventional clinical study within 30 days prior to
screening visit (visit 1) that involved treatment with any drug (excluding
vitamins and minerals) or medical device
- Current alcohol/illicit drug abuse or addiction: history or evidence of
current drug use or addiction (positive urine drug screen for amphetamines,
barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates) or excessive
use of alcohol at screening.
- Positive blood for safety: positive blood test on Hepatitis B, Hepatitis C
and HIV.

Medical conditions
- Eye disease that significantly interferes with fundus examinations in one or
both eyes
- Dilatation of the pupil < 5 mm in the study eye
- Ocular inflammation (including trace or more severe) or conjunctivitis at
screening, or history of uveitis in either eye
- Only one functional eye
- Current use of any medication that might have effect on the coagulation
cascade, hemostasis, and platelets.
o Note: the use of platelet aggregation inhibitors, such as acetyl salicylic
acid or its equivalents, is allowed.
o Note: the use of vitamin K antagonists is allowed given that the INR is
stable between 1-3 over the last 6 months before inclusion.
- History of significant bleeding (gross haematuria, haemoptysis,
gastrointestinal tract bleeding)
- Evidence or history of a hypercoagulable state (e.g. shortened APTT).
- Document history of autoimmune disease with anticipated presence of
potentially pathogenic Annexin A5 antibodies, e.g. antiphospholipid syndrome,
systemic lupus erythematosus or systemic sclerosis.
- Confirmed thalassemia (e.g sickle cell disease)
- Uncontrolled arterial hypertension, defined as systolic blood pressure > 160
mmHg or
diastolic blood pressure > 100 mmHg. One retest of vital functions is allowed
within the screening window.
- Cardiac impairment with an estimated LVEF < 35 % Prolonged QTcF (>450 ms),
cardiac arrhythmias or any clinically significant abnormalities in the resting
ECG at the time of screening, as judged by the investigator
- History of or a currently active hepatic or biliary disease
- History of or a currently active neurological disease
- eGFR (based on plasma-creatinine) outside of normal range at screening or
known renal impairment (<=40 mL/min).
- Any abnormalities in the vital signs of the patient, as judged by the
investigator, as a result of which the patient cannot participate
- Any clinically significant illness, medical/surgical procedure or trauma
within 4 weeks of the administration of IMP.
- Current evidence or history of bacterial, viral or fungal infections within 7
days before ANXV-800CW administration as judged by the Investigator.
o T > = 38.0°C or lab confirmed viral/bacterial/fungal infection (PCR)) or
symptoms suggestive of an infection)
- Any planned major surgery within the duration of the study (until visit 3),
with the exception of any emergency surgeries.
- Any laboratory test which is abnormal, and which is deemed by the
Investigator(s) to be clinically significant
- A history of anaphylaxis, history of allergic reaction(s), known allergy to
one of the drugs or excipients administered as part of this study. Mild
allergies without angio-edema or treatment need can be acceptable if deemed not
to be of clinical significance (including but not limited to allergy to animals
or mild seasonal hay fever)
- Current diagnosis of asthma or reactive airway disease associated with
exercise for which medication is used

Prior therapy
- Any prior systemic anti-VEGF treatment or intravitreal (IVT) anti-VEGF
treatment in the affected eye within a period of 3 months prior to start of the
study
- Any prior intraocular steroid injection in the affected eye within a period
of 3 months prior to start of the study
- Any prior grid or focal laser photocoagulation within 500 microns of the
foveal center
or any prior panretinal photocoagulation (PRP) in the affected eye
- Any intraocular eye surgery in the affected eye within a period of 3 months
prior to start of the study
- Yttrium-Aluminum-Garnet laser treatment performed within 28 days before
screening,
in the affected eye


DR:
General:
- Behavioral or cognitive impairment or psychiatric disease that in the opinion
of the investigator affects the ability of the patient to understand and
cooperate with the study protocol
- Deprived of freedom by an administrative or court order or in an emergency
setting.
- Insufficient venous access for the study procedures.
- Close affiliation with the investigator; e.g. a close relative of the
investigator,
dependent person (e.g. employee or student), employee of the department of
Ophthalmology of the UMCG, TRACER or affiliates
- Any finding in the medical examinations or medical history giving, in the
opinion of the Investigator, reasonable suspicion of a disease or condition
that makes treatment with the investigational drug unadvisable, or that might
affect interpretation of the results of the study or render the patient at high
risk for treatment complications
- Participation in an interventional clinical study within 30 days prior to
screening visit (visit 1) that involved treatment with any drug (excluding
vitamins and minerals) or medical device
- Current alcohol/illicit drug abuse or addiction: history or evidence of
current drug use or addiction (positive urine drug screen for amphetamines,
barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates) or excessive
use of alcohol at screening.
- Positive blood for safety: positive blood test on Hepatitis B, Hepatitis C
and HIV.

Medical conditions
- Eye disease that significantly interferes with fundus examinations in one or
both eyes
- Dilatation of the pupil < 5 mm in the study eye
- Ocular inflammation (including trace or more severe) or conjunctivitis at
screening, or history of uveitis in either eye
- Only one functional eye
- Current use of any medication that might have effect on the coagulation
cascade, hemostasis, and platelets.
o Note: the use of platelet aggregation inhibitors, such as acetyl salicylic
acid or its equivalents, is allowed.
o Note: the use of vitamin K antagonists is allowed given that the INR is
stable between 1-3 over the last 6 months before inclusion.
- History of significant bleeding (gross haematuria, haemoptysis,
gastrointestinal tract bleeding)
- Evidence or history of a hypercoagulable state (e.g. shortened APTT).
- Document history of autoimmune disease with anticipated presence of
potentially pathogenic Annexin A5 antibodies, e.g. antiphospholipid syndrome,
systemic lupus erythematosus or systemic sclerosis.
- Confirmed thalassemia (e.g sickle cell disease)
- Cardiac impairment with an estimated LVEF < 35 % Prolonged QTcF (>450 ms),
cardiac arrhythmias or any clinically significant abnormalities in the resting
ECG at the time of screening, as judged by the investigator
- History of or a currently active hepatic or biliary disease
- History of or a currently active neurological disease
- eGFR (based on plasma-creatinine) outside of normal range at screening or
known renal impairment (<=40 mL/min).
- Any abnormalities in the vital signs of the patient, as judged by the
investigator, as a result of which the patient cannot participate
- Any clinically significant illness, medical/surgical procedure or trauma
within 4 weeks of the administration of IMP.
- Current evidence or history of bacterial, viral or fungal infections within 7
days before ANXV-800CW administration as judged by the Investigator.
o T > = 38.0°C or lab confirmed viral/bacterial/fungal infection (PCR)) or
symptoms suggestive of an infection)
- Any planned major surgery within the duration of the study (until visit 3),
with the exception of any emergency surgeries.
- Any laboratory test which is abnormal, and which is deemed by the
Investigator(s) to be clinically significant
- A history of anaphylaxis, history of allergic reaction(s), known allergy to
one of the drugs or excipients administered as part of this study. Mild
allergies without angio-edema or treatment need can be acceptable if deemed not
to be of clinical significance (including but not limited to allergy to animals
or mild seasonal hay fever)
- Current diagnosis of asthma or reactive airway disease associated with
exercise for which medication is used

Prior therapy
- Any prior systemic anti-VEGF treatment or intravitreal (IVT) anti-VEGF
treatment in the affected eye within a period of 3 months prior to start of the
study
- Any prior intraocular steroid injection in the affected eye within a period
of 3 months prior to start of the study
- Any prior grid or focal laser photocoagulation within 500 microns of the
foveal center
- or any prior panretinal photocoagulation (PRP) in the affected eye within a
period of 3 months prior to start of the study
- Any intraocular eye surgery in the affected eye within a period of 3 months
prior to start of the study
- Yttrium-Aluminum-Garnet laser treatment performed within 28 days before
screening,
in the affected eye