Open-label, Safety, Tolerability and Proof of Concept Study to Evaluate the Use of ANXV (Recombinant Human Annexin A5 Protein) in the Treatment of Patients With Either Diabetic Retinopathy or Recent Onset Retinal Vein Occlusion
Overview
- Phase
- Phase 2
- Intervention
- ANXV
- Conditions
- Not specified
- Sponsor
- Annexin Pharmaceuticals AB
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Safety and tolerability
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
The goal of this clinical trial is to learn about the safety of the investigational medicinal product ANXV. It will also learn about how ANXV works to treat non-proliferative diabetic retinopathy and retinal vein occlusion in adults. The main questions it aims to answer are:
- Is ANXV safe to use?
- Does ANXV improve vision or findings related to vision decrease caused by non-proliferative diabetic retinopathy or retinal vein occlusion?
- Does ANXV lower the number of times participants need to use a rescue medication? Researchers will compare different dose levels of ANXV to see what dose would be be appropriate to test in larger studies.
Participants will:
Take ANXV as a 30 minutes infusion (slow injection) for 5 days. Visit the clinic for checkups and tests at 11 visits during 4 months.
Detailed Description
The study is an open label, prospective, dose evaluation study to investigate the safety, tolerability and efficacy in patients with Non-Proliferative Diabetic Retinopathy (NPDR) or Retinal Rein Occlusion with recent onset (within 28 days from symptoms onset or diagnosis (whichever is first) to first treatment). The study consists of 11 visits, whereof one screening visit, five treatment visits and five follow up visits, during a 4 months period. Intervention is intravenous infusion (30 minutes) with the investigational medicinal product ANXV, a recombinant Annexin A5 protein. The intended dose levels are 4 mg, 1 mg and 6 mg, daily administration for five days. Safety will be regularly evaluated by the Medical Monitors on a per need basis, as data become available. In case of safety concerns within one indication subset (NPDR and RVO), a lower dose will be initiated within the concerned indication subset (for each subset, independently). The following assessments will be performed: Ocular assessments: * BCVA * OCT and OCTA * ERG * UWF-retinal imaging * UWF-FFA * Ocular examination - Slit Lamp biomicroscopy examination, Intraocular Pressure (IOP), RAPD * Dilated indirect ophthalmoscopy Non-ocular assessments: * Vital signs * ECG * Safety labs (blood and urine) * Study labs (blood)
Investigators
Eligibility Criteria
Inclusion Criteria
- •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:
Exclusion Criteria
- •An individual who meets any of the following criteria will be excluded from participation in this trial:
- •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
- •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
- •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
- •Prior exposure to a recombinant Annexin A5 protein
- •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)
- •Current use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib) or corticosteroids
- •Diagnosed untreated systemic metastasis malignancy
- •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
Arms & Interventions
RVO, 4mg, 5 doses
ANXV 4mg 30 min infusion
Intervention: ANXV
NPDR, 6 mg, 5 doses
ANXV 6mg 30 min infusion
Intervention: ANXV
RVO, 4 mg, 3 doses
ANXV 4mg 30 min infusion
Intervention: ANXV
NPDR, 4mg, 5 doses
ANXV 4mg 30 min infusion
Intervention: ANXV
Outcomes
Primary Outcomes
Safety and tolerability
Time Frame: From day 1 to day 120
* Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) * Incidence and titre of anti-drug antibodies (ADA) to ANXV pre- and post-administration
Secondary Outcomes
- Anti-drug antibody(From day 1 to day 120)
- Proof of concept(From day 1 to day 120)
- Rescue medication use(From day 1 to day 120)
- ANXV concentration(From start of administration up to four hours after start of administration, during all treatment days)