retinal vein occlusion and diabetic retinopathy
Conditions
Interventions
All patients will undergo a standard of care ophthalmological work-up to
establish the diagnosis of RVO/DR: Best Corrected Visual Acuity (BCVA),
Tonometry, slit lamp biomicroscopy, fundoscopy, Optic
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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 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 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 m
Exclusion criteria
Exclusion criteria: 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 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To asses the safety and tolerability of intravenous administration of ANXV-800CW (in 3 doses: 0.5 mg, 1.0 mg, 2.0 mg flat dose) in patient with RVO/DR. This will be done by monitoring and evaluating whether (serious) adverse events (S-)AEs) and suspected unexpected serious adverse reactions (SUSARs) have occurred. These are defined as clinically significant changes in: - Vital signs: blood pressure, heart rate, respiratory rate, body temperature - Safety laboratory parameters such as incidence and titre of Anti-Drug Antibodies ADA to ANXV To asses the feasibility of fluorescent imaging for visualization/targeting of ANXV-800CW in 3 doses (0.5 mg, 1.0 mg, 2.0 mg flat dose) in RVO/DR patients, using a Near-Infrared (NIR) fluorescent imaging system. For this the target-to-background ratio will be determined of the fluorescent signal by using rbitrary Units (AUs)right before intravenous injection of ANXV-800CW and at 5 minutes, 10 minutes, 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours and 4 hours following administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| To asses the pharmacokinetic profile of ANXV-800CW (3 doses: 0.5 mg, 1.0 mg, 2.0 mg flat dose) in patients with RVO/DR. This will be done, 5, 10, 20,30 minutes, 1 hour, 1.5 hours, 2 hours and 4 hours post administration: - Area under the plasma concentration vs time curve from time zero extrapolated to infinity (AUCinf) - AUC from time zero to time of last quantifiable analyte concentration (AUClast) - Observed maximum concentration (Cmax) - Time to Cmax (Tmax) - Terminal slope of a semi-logarithmic concentration-time curve (*z) - Terminal half life (T*) - Clearance (CL) - Volume of distribution (Vz) - Dose proportionality after a single dose, based on AUC and Cmax if several dose levels are investigated In addition, this study will look at the PS availability, as measured with Flow Cytometry right before and after ANXV-800CW administration. | — |
Countries
Netherlands
Outcome results
None listed