Comparison of Pharmacokinetics of and Effect on Systemic VEGF Levels in Age Related Macular Degeneration Patients

Phase 2

• Conditions: Age Related Macular Degeneration
• Interventions: Drug: Ranibizumab; Drug: Aflibercept; Other: Control Group; Drug: Bevacizumab

• Registration Number: NCT02296567
• Lead Sponsor: East Florida Eye Institute

Brief Summary

To demonstrate the effects of Lucentis (ranibizumab), Avastin ( bevacizumab), and Eylea ( aflibercept) on the levels of naturally occurring Vascular Endothelial Growth Factor (VEGF) in the systemic circulation of Age Related Macular Degeneration patients currently treated with these medications.

Detailed Description

To determine plasma levels of VEGF and serum Pharmacokinetic (PK) levels after varying lengths of time following intravitreal injection with Avastin, Lucentis, or Eylea in exudative macular degeneration. Patients will be tested while following a normal course of treatment in our institute. All screenings and testing will be conducted in three study visits.

Study Timeline

• Study First Submitted: 2014-11-05
• Study First Submitted QC: 2014-11-18
• Study First Posted: 2014-11-20
• Study Start: 2014-12
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-07
• Last Update Posted: 2015-08-11
• Primary Completion: 2016-07
• Study Completion: 2016-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Ability to provide written informed consent for participation in this study.
2. Adults ≥ 50 years of age with exudative macular degeneration treated with Avastin, Lucentis, or Eylea in previously determined time intervals exclusive to a single anti-VEGF treatment type for not than three months.
3. CONTROL GROUP: Age matched control group with no previously diagnosed exudative macular degeneration will also be enrolled.
4. Provide signed informed consent.

Exclusion Criteria

1. Uncontrolled blood pressure (defined as systolic > 160mm Hg or Diastolic > 95mm Hg while patient is sitting)
2. Uncontrolled diabetes mellitus defined by Hemoglobin A1c (HbA1C > 12% at screening)
3. Concomitant ocular or systemic administration of drugs that may interfere with or potentiate the mechanism of action of anti-VEGF medications.
4. Previous administration of systemic anti-angiogenic medications within 3 months
5. Participation in a simultaneous medical investigation or trial.
6. Treatment within 2 months with anti-VEGF agent in the fellow eye or anticipated need for further treatment during the study.
7. Patients with any cancer diagnosis in remission for less than five years with the exception that patients with skin cancers, basal cell or squamous cell, treated exclusively or topical treatment will be allowed.
8. Female patients who have not reached menopause, defined as cessation of menses for a minimum of twelve months with no perimenopausal symptoms.
9. Patients who have significant wound healing during the trial.
10. Patients with a history of vitrectomy in the study eye.
11. patients with uncontrolled psoriasis, rheumatoid arthritis, osteoarthritis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 Lucentis 4 weeks	Ranibizumab	Blood samples will be collected from patients receiving ranibizumab following the first dose of standard care therapy.
Group 3 Eylea 4 weeks	Aflibercept	Blood samples will be collected from patients receiving aflibercept following the first dose of standard care therapy.
Group 4 Lucentis 6 weeks	Ranibizumab	Blood samples will be collected from patients receiving ranibizumab following the first dose of standard care therapy.
Group 10 Control Group no treatment	Control Group	Blood samples will be collected from patients who are not receiving anti-VEGF treatment.
Group 2 Avastin 4 weeks	Bevacizumab	Blood samples will be collected from patients receiving bevacizumab following the first dose of standard care therapy.
Group 6 Eylea 6 weeks	Aflibercept	Blood samples will be collected from patients receiving aflibercept following the first dose of standard care therapy.
Group 5 Avastin 6 weeks	Bevacizumab	Blood samples will be collected from patients receiving bevacizumab following the first dose of standard care therapy.
Group 7 Lucentis 8 weeks	Ranibizumab	Blood samples will be collected from patients receiving ranibizumab following the first dose of standard care therapy.
Group 8 Avastin 8 weeks	Bevacizumab	Blood samples will be collected from patients receiving bevacizumab following the first dose of standard care therapy.
Group 9 Eylea 8 weeks	Aflibercept	Blood samples will be collected from patients receiving aflibercept following the first dose of standard care therapy.

Primary Outcome Measures

Name	Time	Method
Change in serum and plasma levels of free Vascular Endothelial Growth Factor	up to 8 weeks	Serum and plasma levels of free vascular endothelial growth factor will be measured up to 8 weeks following the standard of care treatment.

Secondary Outcome Measures

Name	Time	Method
Change in Serum drug levels in nanomoles (nM) units following treatment	8 weeks	Serum levels of Ranibizumab, Bevacizumab, or Aflibercept will be measured up to 8 weeks following the standard of care treatment.
Amount of fluid (cubic mm) as measured by Ocular Coherence Tomography in the contralateral eye will be correlated with systemic Vascular Endothelial Growth Factor levels	8 weeks

Trial Locations

Locations (1)

East Florida Eye Institute; 🇺🇸 Stuart, Florida, United States