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

NCT05532735 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: ANN-004
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 7

Brief Summary

Open-label, dose ascending safety, tolerability, and proof of concept study to evaluate the use of ANXV (human recombinant Annexin A5) in the treatment of subjects with recently diagnosed Retinal Vein Occlusion.

Conditions

Retinal Vein Occlusion

Outcome Measures

Primary Outcomes (2)

• Safety - Treatment Emergent Adverse Events

  Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  120 days

• Safety - Anti-drug antibodies

  Incidence and titer of anti-drug antibodies (ADA) to ANXV pre- and post-administration

  120 days

Secondary Outcomes (28)

• Safety - Slit lamp

  120 days

• Safety - Gonioscopy

  120 days

• Safety - Best Corrected Visual Acuity (BCVA)

  120 days

• Safety - laboratory parameters

  15 days

• Safety - vital signs Blood Pressure

  15 days

Other Outcomes (2)

• ANXV binding sites

  43 days

• Endogenous Annexin A5

  43 days

Study Arms (5)

2 mg ANXV

EXPERIMENTAL

ANXV (human recombinant Annexin A5), infusion, 2 mg daily during five days.

Biological: ANXV

4 mg ANXV

EXPERIMENTAL

ANXV (human recombinant Annexin A5), infusion, 4 mg daily during five days.

Biological: ANXV

1 mg ANXV

EXPERIMENTAL

ANXV (human recombinant Annexin A5), infusion, 1 mg daily during five days.

Biological: ANXV

6 mg ANXV

EXPERIMENTAL

ANXV (human recombinant Annexin A5), infusion, 6 mg daily during five days.

Biological: ANXV

8 mg ANXV

EXPERIMENTAL

ANXV (human recombinant Annexin A5), infusion, 8 mg daily during five days.

Biological: ANXV

Interventions

ANXV BIOLOGICAL

ANXV (Human recombinant Annexin A5 protein)

1 mg ANXV; 2 mg ANXV; 4 mg ANXV; 6 mg ANXV; 8 mg ANXV

Eligibility Criteria

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

You may qualify if:

• 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 must be non-pregnant and non-lactating, and either surgically sterile (e.g., ≥6 weeks post bilateral salpingectomy, bilateral oophorectomy with or without hysterectomy) or post-menopausal (12 months of spontaneous amenorrhea in females \> 55years of age or, in females ≤55 years, or 12 months of spontaneous amenorrhea without an alternative medical, or 12 months with an elevated Follicle Stimulating Hormone (FSH) level Males must either be surgically sterile or abstinent\*, or if engaged in sexual relations with a female of child-bearing potential, the subject or the subject's non-pregnant female partner must use a highly effective contraception method from the time of signing the Informed Consent Form (ICF) until at least 30 days after the last dose of study drug; Refer to Section 10.3 for acceptable methods
• \*Abstinence is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods). Declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception (Section 10.3).
• Onset of symptoms of Retinal Vein Occlusion within 23 days prior to informed consent
• The criterion has been removed
• The criterion has been removed
• Clear ocular media and adequate pupillary dilation in the Study Eye to permit high quality retinal imaging
• Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) for at least 72 hours prior to study visits
• A negative rapid SARS-CoV-2 (COVID) test on Day 1 prior to initiation of study drug infusion

You may not qualify if:

• Subjects will not be eligible if they have any of the following criteria:
• Study Eye only:
• A severe (≥0.9 log, Grade 3+ or worse) Relative Afferent Pupillary Defect (RAPD)
• Evidence of deep intraretinal hemorrhage involving the center 1mm of the macula
• Evidence of neovascularization
• 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, clinically significant diabetic macular edema, retinal detachment, macular hole, vitreomacular traction, macular epiretinal membrane, clinically significant cataract, vitreal opacities or hemorrhage, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa or choroidal neovascularization of any cause (e.g., Age-related Macular Degeneration (AMD), ocular histoplasmosis, toxoplasmosis, or pathologic myopia)
• Laser photocoagulation in the study eye within the preceding 6 months prior to the Screening Visit
• Receipt within the past 6 months prior to the Screening Visit of any intraocular surgery (including refractive surgery, cataract surgery), or intravitreal (IVT) injection, or planned intraocular surgery or procedure during the study, unless approved by Medical Monitor or Sponsor
• Recent (6 months) history, or current evidence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus), unless approved by Medical Monitor or Sponsor
• Fellow Eye:
• BCVA in the Fellow eye of ≤70 ETDRS letters (approximately 20/40 or less), unless approved by the Medical Monitor or the Sponsor
• Both Eyes:
• Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens, or optic nerve (e.g., desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol)
• 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-edema 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)
• An IOP greater than 24 mmHg that is not controlled with medication or surgery at the time of the Screening Visit

Sponsors & Collaborators

• Annexin Pharmaceuticals AB: lead
• InFocus Clinical Research: collaborator

Study Sites (7)

Eye Associates of Northeast Louisiana

West Monroe, Louisiana, 71219, United States

Location

Cumberland Valley Retina Consultants

Hagerstown, Maryland, 21740, United States

Location

Tulsa Retina Consultants

Tulsa, Oklahoma, 74114, United States

Location

Retina Consultants of Texas

Bellaire, Texas, 77401, United States

Location

Valley Retina Institute

McAllen, Texas, 78503, United States

Location

Retina Consultants of Texas

San Antonio, Texas, 78240, United States

Location

Virginia Retina Center

Warrenton, Virginia, 20186, United States

Location

MeSH Terms

Conditions

Retinal Vein Occlusion

Condition Hierarchy (Ancestors)

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

Study Officials

• Anna Frostegård

  Annexin Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: September 8, 2022
• Study Start: August 24, 2022
• Primary Completion: July 17, 2024
• Study Completion: November 11, 2024
• Last Updated: December 11, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)