NIR Fluorescence Molecular Imaging of ANXV-800CW in RVO Patients

NCT05133791 | Unknown Phase 1 DMC

• 1 other identifier: 2021-000866-13
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is safety, tolerability and feasibility of systemic intravenous injection of ANXV-800CW in patients with RVO in three dosing-cohorts in a phase I safety study. Secondary objectives are to determine in the pre-mentioned dosing-cohorts the pharmacokinetic profile of ANXV-800CW and to determine phosphatidylserine availability as measured by flow cytometry in whole blood before and after ANXV-800CW administration. Study design: non-randomized, non-blinded, prospective, mono-center safety/ feasibility dose optimization study Study population: Patients referred for (sub-)acute blurred vision with the diagnosis of RVO aged 18-85 years, fertile females excluded. Intervention: All patients will undergo a standard of care ophthalmological work-up to establish the diagnosis of RVO. In the context of this study, Fluoresceine Angiography (FA) will be added to the ophthalmological work-up for all patients. Furthermore, the patients will receive a systemic single-dose injection of ANXV-800CW as part of a optimization study, followed by NIR retinal fluorescence imaging. Main study parameters/endpoints: The main study parameters studies are safety, tolerability and feasibility of near-infrared fluorescent imaging in the retina of patients with RVO related to the systemic injection of ANXV-800CW.

Conditions

Retinal Vein Occlusion

Keywords

Near Infra red (NIR); Fluorescence molecular imaging; Annexin A5-800CW

Outcome Measures

Primary Outcomes (3)

• Safety of near-infrared fluorescent imaging in the retina of patients with RVO related to the systemic injection of ANXV-800CW

  Safety will be assessed by looking at AEs,SAEs, and SUSARs as identified by a questionnaire, but also by looking at vital signs: blood pressure (mmHg), heart rate (beats per minute), temperature (degrees celsius) respiratory rate (breaths per minute)

  1.5 years

• Tolerability of near-infrared fluorescent imaging in the retina of patients with RVO related to the systemic injection of ANXV-800CW

  Tolerability will be assessed by looking at AEs,SAEs, and SUSARs as identified by a questionnaire, but also by looking at vital signs: blood pressure (mmHg), heart rate (beats per minute), temperature (degrees celsius) respiratory rate (breaths per minute)

  1.5 years

• Feasibility of near-infrared fluorescent imaging in the retina of patients with RVO related to the systemic injection of ANXV-800CW

  Fluorescence intensity (Arbitrary Units) will be measured by using the NIR imaging system and the target to background ratio (reported as the mean, SD, and range) will be calculated from fluorescence images

  1.5 years

Study Arms (3)

0.5 mg

ACTIVE COMPARATOR

Annexin A5-CW800, 0.5 mg, 1 dose

Drug: Annexin A5

1.0 mg

ACTIVE COMPARATOR

Annexin A5-CW800, 1.0 mg, 1 dose

Drug: Annexin A5

2.0 mg

ACTIVE COMPARATOR

Annexin A5-CW800, 2.0 mg, 1 dose

Drug: Annexin A5

Interventions

Annexin A5 DRUG

Annexin A5 coupled to IRDye800CW as a potential treatment for RVO

Also known as: Flurescein Angiography

0.5 mg; 1.0 mg; 2.0 mg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≤ 30.0 kg/m2 and weight at least 50 kg and no more than 100 kg at screening.
• 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:
• At least 1 year post-menopausal (amenorrhea \>12 months and/or follicle-stimulating hormone \>30 mIU/mL) at screening;
• Surgically sterile (bilateral oophorectomy, hysterectomy, or tubal ligation);
• 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.

You may not qualify if:

• 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
• Plasma donation within one month of visit 1 or blood donation of \>450 ml during the three months prior to visit 1
• 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
• Previous confirmed COVID19 disease requiring hospital care or positive COVID19 test at visit 1.
• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

UMCG

Groningen, 9700RB, Netherlands

RECRUITING

MeSH Terms

Conditions

Retinal Vein Occlusion

Interventions

Annexin A5

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Annexins; Calcium-Binding Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins

Central Study Contacts

Yester Janssen, MD

CONTACT

+31615170900; y.f.janssen@umcg.nl

Hendrikus Boersma, PharmD, PhD

CONTACT

h.h.boersma@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: non-randomized, non-blinded, prospective, mono-center safety/ feasibility dose optimization study

Study Record Dates

• First Submitted: September 16, 2021
• First Posted: November 24, 2021
• Study Start: September 23, 2021
• Primary Completion: January 1, 2024
• Study Completion: May 1, 2024
• Last Updated: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)