Study Evaluating the Efficacy of Aflibercept for the Treatment of Inflammatory CNV in Young Patients (ALINEA). (ALINEA)

Phase II Study Evaluating the Efficacy of Aflibercept for the Treatment of Inflammatory Choroidal Neovascularization (CNV) in Young Patients.

Inflammatory choroidal neovascularization (InCNV) is the third cause of CNV after myopia and Age-related Macular Degeneration (AMD). InCNV is a rare but severe disease and its treatment should not be delayed.

InCNV is treated at the moment with off-label anti-VEGF (Vascular Endothelial Growth Factor) therapy and could also benefit from aflibercept (EYLEA), a new anti-VEGF currently indicated in AMD. Case reports suggest that such patients would not need as many injections as in AMD.

ALINEA is an open-label, single arm, prospective, multicenter, phase II study. The main objective is to demonstrate the effectiveness in clinical terms after 52 weeks of treatment with aflibercept on the visual acuity of patients affected by InCNV. A specific dosage regimen is designed to achieve maximum efficiency. The patients are followed on a monthly basis until 52 weeks. The first injection is mandatory. The other ones are injected only in case of active InCNV.

Study Overview

• Status: Completed
• Conditions: Inflammatory Choroidal Neovascularization
• Intervention / Treatment: Drug: Aflibercept

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69004
    • Hospices Civils de Lyon / Hôpital de la Croix Rousse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 < Age < 60 years old
• Patient who give voluntary signed informed consent
• Patient affiliated with the French universal health care system or similar
• Patient with inflammatory CNV, whatever the cause, including multifocal choroiditis, punctate inner choroidopathy, ocular toxoplasmosis, serpiginous choroiditis or Birdshot chorioretinopathy with active primary subfoveal, retrofoveal or juxtafoveal lesions that affect the fovea as evidenced by angiography (fluorescein and/or indocyanine green) and/or SD-OCT in the studied eye
• Patient willing, committed and able to return for all clinic visits and complete all study-related procedures

Exclusion Criteria:

• Pregnant women
• Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception during the study
• Patient who is protected adults according to the terms of the law (French public health laws)
• Involvement in another clinical trial (studied eye and/or the other eye)

• Patient with non-inflammatory CNV, especially:

  • AMD
  • drusen associated with neovessel
  • High myopia defined as refraction ≥ - 6 diopters
• Other curative treatment of inflammatory CNV in the studied eye during the last 3 months before the first intravitreal injection: anti-VEGF therapy, juxta- or extra-foveal macular laser, photodynamic therapy, surgery, external radiotherapy, transpupillary thermotherapy ...
• Medical history of retrofoveal focal macular laser photocoagulation in the studied eye
• Subretinal hemorrhage reaching the fovea center or with a size > 50% of the lesion area
• Fibrosis or retrofoveal retinal atrophy in the studied eye
• Retinal pigment epithelial tear reaching the macula in the studied eye
• Medical history of intravitreal medical device in the studied eye
• Medical history of auto-immune or idiopathic uveitis
• Proved diabetic retinopathy
• Intra-ocular pressure ≥ 25 mmHg despite two topical hypotonic treatments
• Aphakia or lack of lens capsule (not removed by YAG (yttrium aluminium garnet) laser) in the studied eye
• Arterial hypertension that is not controlled by an appropriate treatment and defined by one measure of systolic blood pressure > 180mmHG or 2 consecutive measures > 160mmHg, or by a diastolic blood pressure > 100mmHg
• Antecedents of cerebrovascular disease or myocardial infarction during the last 6 months before inclusion (J1)
• Antecedents of any pathology, metabolic disease, or any serious suspicion of disease during the clinical or laboratory exam that would contraindicate the use of the product, could affect the interpretation of the study results or lead to major risks of complication for the subject
• Renal insufficiency requiring dialysis or renal transplantation
• Previous (less than a year) or actual treatment with systemic administration of anti-VEGF therapy
• Known hypersensitivity to aflibercept, or another drug composite of the medicinal product used; allergy to fluorescein, indocyanine green, anaesthetic eye drops
• Active or suspected ocular or peri-ocular infection
• Medical history of intra-ocular surgery within 28 days before the first injection in the studied eye
• Any illness or ocular condition that would require an intra-ocular surgery in the studied eye within 12 months after the inclusion
• Follow up not possible during 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aflibercept; Intravitreal injection of aflibercept (EYLEA) / 2mg	Drug: Aflibercept; The patients are followed on a monthly basis until 52 weeks. Intravitreal injections of aflibercept at a dosage of 2 mg are initiated at inclusion (mandatory injection) with reinjection every 4 weeks only in case of CNV activity (PRN regimen) until 52 weeks.Therefore, each patient receives between 1 and 13 injections in the whole study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in best-corrected visual acuity (BCVA) expressed as number of letters gained or lost measured with Early Treatment Diabetic Retinopathy Study (ETDRS) scale from baseline to week 52	BCVA is measured on the ETDRS scale at an initial distance of 4 meters	52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean change in BCVA expressed as number of letters gained or lost measured with ETDRS scale from baseline to week 24	24 weeks
Percentage of patients with a <15-letter loss in BCVA measured with ETDRS scale from baseline to week 24	24 weeks
Percentage of patients with a <15-letter loss in BCVA measured with ETDRS scale from baseline to week 52	52 weeks
Number of injections per patient	52 weeks
Mean time between 2 injections	52 weeks
Mean change in central retinal thickness (CRT) in micrometers measured with Spectral Domain - Optical Coherence Tomography (SD-OCT) from baseline to week 24	24 weeks
Mean change in central retinal thickness (CRT) in micrometers measured with Spectral Domain - Optical Coherence Tomography (SD-OCT) from baseline to week 52	52 weeks
Mean change in neovascular lesion size measured with fluorescein and/or indocyanine green angiography from baseline to week 52	52 weeks
Side-effects observed during the study	52 weeks
Mean change in neovascular lesion morphology measured with fluorescein and/or indocyanine green angiography from baseline to week 52	52 weeks

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Publications and helpful links

General Publications

• Kodjikian L, Abukhashabah A, Fardeau C, Tadayoni R, Brezin A, Dumas S, Weber M, Bernard L, Loria O, Decullier E, Huot L, Mathis T. Efficacy and safety of Aflibercept for the treatment of inflammatory choroidal neovascularization: The ALINEA study. Acta Ophthalmol. 2023 Feb;101(1):e43-e49. doi: 10.1111/aos.15214. Epub 2022 Jul 13.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: September 18, 2015
• First Submitted That Met QC Criteria: September 18, 2015
• First Posted (Estimated): September 22, 2015

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Aflibercept; young patient; inflammatory choroidal neovascularization
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Uveal Diseases; Choroid Diseases; Metaplasia; Choroidal Neovascularization; Neovascularization, Pathologic; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: 69HCL14_0201; 2014-003695-23 (EudraCT Number)