Pharmacogenomics of antiVEGF in Patients With Age-Associated Macular Degeneration (AMD)

NCT06952452 | Recruiting Phase 3

• 2 other identifiers: ICI21/000252019-003204-12
• Study Type: interventional
• Target: 630
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase III, multicenter, randomized double-blinded clinical trial with two parallel groups (ranibizumab and bevacizumab) and an observational follow-up of patients who meet elegibility criteria and decline participation due to treatment randomization. It will be performed involving 630 eyes from patients with wet age-related macular degeneration (wAMD) diagnosis without another eye disease. This clinical trial compares the treatment response for 3 years, considering genetic variants already studied between the eyes treated with one of the first options of anti-VEGF used in patients with wAMD, (ranibizumab) and the most cost-effective anti-VEGF (bevacizumab; off-label use)

Conditions

Wet Age-related Macular Degeneration

Keywords

wAMD; antiVEGF; BVZ; RBZ; AMD; pharmacogenomics

Outcome Measures

Primary Outcomes (1)

• Frequency of Genetic Polymorphism in VEGFA Associated With Anti-VEGF Treatment Response in AMD Patients

  Proportion of patients carrying the VEGFA genetic polymorphism (VEGFA, CFH, CTFG, ARMS2, HTRA1, OR52B4, LOC387715, LOC100287225, LEPR, SERPINF1), as determined by genotyping of DNA extracted from saliva samples. This measure will be correlated with response to anti-VEGF therapy (ranibizumab or aflibercept). Unit of Measure: % of participants with polymorphism. Measurement Tool: Genotyping assay on saliva-derived DNA (e.g., TaqMan PCR-based method).

  From baseline, first dose, up to 3 years

Secondary Outcomes (11)

• Change in Visual Acuity Over Time in Patients With AMD Receiving Anti-VEGF Therapy

  Baseline, 6 months, 12 months, 24 months, 36 months

• Change in Retinal Fluid and Foveal Thickness Over Time as Measured by OCT in Patients With AMD Treated With Anti-VEGF Therapy

  Baseline, 6 months, 12 months, 24 months, 36 months

• Distribution of Sex Among Patients With AMD Receiving Anti-VEGF Therapy

  At baseline

• Distribution of Age at Diagnosis in Patients With AMD Receiving Anti-VEGF Therapy

  At baseline

• Proportion of Smokers Among Patients With AMD Receiving Anti-VEGF Therapy

  At baseline

Study Arms (2)

Bevacizumab, BVZ (group A)

EXPERIMENTAL

A cycle of 3 intravitreal injections every 4-6 weeks of BVZ

Drug: Bevacizumab

Ranibizumab, RBZ (group B)

ACTIVE COMPARATOR

A cycle of 3 intravitreal injections every 4-6 weeks of RBZ

Drug: Ranibizumab Ophthalmic

Interventions

Bevacizumab DRUG

The dosage for each intravitreal injection is 1.25mg of BVZ in 0.05ml

Also known as: Avastin, L01XC07

Bevacizumab, BVZ (group A)

Ranibizumab Ophthalmic DRUG

The dosage for each intravitreal injection contains 0.5mg of RBZ in 0.05ml

Also known as: Lucentis, S01LA04

Ranibizumab, RBZ (group B)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with neovascular Age-related Macular Degeneration
• Age of 50 years or older.
• That at the discretion of the ophthalmologist has an indication of receiving treatment with an anti-VEGF agent as usual in clinical practice.
• Without previous treatment in the eye under study (no previous treatment for AMD).

You may not qualify if:

• Participate or have participated in another clinical trial with an experimental drug in the last 6 months.
• Patients with other eye diseases, p. eg, advanced glaucoma or visually significant cataracts, which are likely to require surgery during the follow-up period in the eye under study.
• Concomitant, ocular or systemic, administration of drugs up to 3 months before the treatment with another anti-VEGF in the contralateral eye.
• High cardiovascular risk: poorly controlled arterial hypertension, history or risk of arterial thromboembolic events, history of stroke or acute myocardial infarction, anticoagulant treatment, proteinuria or major elective surgery within 3 months.
• Ophthalmological risk with the intraocular injection (all intravitreal treatments): active or suspected ocular or periocular infection, severe blepharitis, history of endophthalmitis, history of retinal detachment, myopathy, glaucoma.
• Hypersensitivity to the active substance or to the excipients.
• Diabetic retinopathy documented.
• Pregnant or nursing (lactating) women.
• Patients who meet elegibility criteria and decline participation due to treatment randomization, will participate in an observational follow-up, collecting saliva for the analysis of genetic polymorphisms and clinical data related to antiVEGF received out of the clinical trial and AV, OCT results and adverse events registered in medical records at 6m, 12m, 24m, 36m.

Sponsors & Collaborators

• Parc de Salut Mar: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (4)

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

RECRUITING

Hospital la Esperanza

Barcelona, Spain

RECRUITING

Unidad Central de Investigación Clínica y Ensayos Clínicos (UCICEC La Paz)

Madrid, 28046, Spain

RECRUITING

MeSH Terms

Interventions

Bevacizumab; Ranibizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ana Aldea

CONTACT

+3431604900; aaldea@imim.es

Melina Rojas

CONTACT

mrojas@researchmar.net

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 1:1 into one of two treatment arms: ranibizumab or bevacizumab. Patients who meet elegibility criteria and decline participation due to treatment randomization, will participate in an observational follow-up.

Study Record Dates

• First Submitted: October 28, 2024
• First Posted: April 30, 2025
• Study Start: November 18, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: November 20, 2025

Record last verified: 2025-11

Locations

ES (4)