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Systemic Vascular Endothelial Growth Factor (VEGF) Protein Dynamics Following Intravitreal Injections of Ranibizumab Versus Aflibercept in Patients With Neovascular Age-related Macular Degeneration (TIDE AMD)

Primary Purpose

Wet Age-Related Macular Degeneration

Status

Completed

Phase

Phase 4

Locations

Germany

Study Type

Interventional

Intervention

Ranibizumab 0.5 mg

Aflibercept 2 mg

About this trial

This is an interventional treatment trial for Wet Age-Related Macular Degeneration

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Visual impairment predominantly due to neovascular AMD.
Active, newly diagnosed, untreated, angiographically documented, CNV lesion (i.e. leakage on fluorescein angiography plus intraretinal, subretinal or sub-RPE fluid on OCT) secondary to neovascular AMD in line with SmPC of ranibizumab and aflibercept

Exclusion Criteria:

Stroke or myocardial infarction less than 3 months prior to screening.
Presence of uncontrolled systolic blood pressure or diastolic blood pressure
Type 1 or Type 2 diabetes mellitus
Use of any systemic anti-VEGF drugs
Use of systemic or inhaled corticosteroids for at least 30 consecutive days within 3 months prior to screening.
Women who are pregnant or breast feeding or who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception

For either eye:

Any active periocular or ocular infection or inflammation
Uncontrolled glaucoma
Neovascularization of the iris or neovascular glaucoma
History of treatment with any anti-angiogenic drugs

For study eye:

Atrophy or fibrosis involving the center of the fovea at the time of screening or baseline.
Cataract (if causing significant visual impairment), planned cataract surgery during the study period, vitrectomy, aphakia, glaucoma surgery, severe vitreous hemorrhage, rhegmatogenous retinal detachment, proliferative retinopathy or choroidal neovascularization of any other cause than wAMD
Irreversible structural damage within 0.5 disc diameter of the center of the macula
Any intraocular procedure (including cataract surgery, Yttrium-Aluminum-Garnet capsulotomy) within 3 months prior to baseline or anticipated within the next 6 months following baseline.
Use of intravitreal or topical ocular corticosteroids administered for at least 30 consecutive days within 3 months prior to screening.

For fellow eye

- Retinal or choroidal neovascularization or macula edema of any cause

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group 1

Group 2

Arm Description

6 monthly intravitreal injections of 0.5 mg ranibizumab

3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab

Outcomes

Primary Outcome Measures

Standardized Area Under the Curve (AUC) for VEGF A Levels by SIMOA (Quanterix's Single Molecule Array) Method for the Comparative Phase

The AUC was calculated using the trapezoidal rule, where all available measurement between Day 1 and Week 12 were used. The AUC was standardized by dividing the calculated value by the number of days from first to last measurement.

Secondary Outcome Measures

Systemic VEGF-A Protein Levels From Study Week 12 to 24

Systemic VEGF-A protein levels in patients switching from monthly 2 mg aflibercept injections to monthly 0.5 mg ranibizumab compared to patients treated with monthly 0.5 mg ranibizumab from baseline (standardized area under the curve)

Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)

Adjustment of systemic VEGF-A levels of patients switching from aflibercept to ranibizumab to levels comparable to baseline or to levels comparable as in patients treated from baseline with ranibizumab

Full Information

NCT ID

NCT02257632

First Posted

October 2, 2014

Last Updated

January 31, 2019

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02257632

Brief Title

Systemic Vascular Endothelial Growth Factor (VEGF) Protein Dynamics Following Intravitreal Injections of Ranibizumab Versus Aflibercept in Patients With Neovascular Age-related Macular Degeneration

Acronym

TIDE AMD

Official Title

A Randomized, Single-blinded, Multicenter, Phase IV Study to Compare Systemic VEGF Protein Dynamics Following Monthly Intravitreal Injections of 0.5 mg Ranibizumab Versus 2 mg Aflibercept Until Study Week 12 in Patients With Neovascular (Wet) Age-related Macular Degeneration

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

April 8, 2015 (Actual)

Primary Completion Date

March 20, 2017 (Actual)

Study Completion Date

June 8, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of the study was to compare the effect of intravitreal injections of ranibizumab and aflibercept on systemic VEGF protein levels in treatment naïve wet neovascular Age-related Macular Degeneration (wAMD) patients in a detailed time course.

Detailed Description

A planned study visit schedule was established at the time of baseline visit (day 1) for all patients. Study assessments for patients were performed at screening visit, baseline (day 1), day 2, day 8 (± 1 day to allow for flexibility in scheduling) and as of day 15 through to day 169 at biweekly visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Wet Age-Related Macular Degeneration

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

41 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

6 monthly intravitreal injections of 0.5 mg ranibizumab

Arm Title

Group 2

Arm Type

Experimental

Arm Description

3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab

Intervention Type

Drug

Intervention Name(s)

Ranibizumab 0.5 mg

Other Intervention Name(s)

Lucentis

Intervention Description

Administered as an intravitreal injection

Intervention Type

Drug

Intervention Name(s)

Aflibercept 2 mg

Other Intervention Name(s)

Eylea

Intervention Description

Administered as an intravitreal injection

Primary Outcome Measure Information:

Title

Standardized Area Under the Curve (AUC) for VEGF A Levels by SIMOA (Quanterix's Single Molecule Array) Method for the Comparative Phase

Description

Time Frame

Baseline up to Week 12 visit (Days 1, 2, 8, 15, 29, 43, 57, 71, 85)

Secondary Outcome Measure Information:

Title

Systemic VEGF-A Protein Levels From Study Week 12 to 24

Description

Time Frame

From study week 12 to 24 (Days 85, 99, 113, 127, 141, 155, 169)

Title

Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)

Description

Time Frame

From study week 12 to 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Visual impairment predominantly due to neovascular AMD. Active, newly diagnosed, untreated, angiographically documented, CNV lesion (i.e. leakage on fluorescein angiography plus intraretinal, subretinal or sub-RPE fluid on OCT) secondary to neovascular AMD in line with SmPC of ranibizumab and aflibercept Exclusion Criteria: Stroke or myocardial infarction less than 3 months prior to screening. Presence of uncontrolled systolic blood pressure or diastolic blood pressure Type 1 or Type 2 diabetes mellitus Use of any systemic anti-VEGF drugs Use of systemic or inhaled corticosteroids for at least 30 consecutive days within 3 months prior to screening. Women who are pregnant or breast feeding or who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception For either eye: Any active periocular or ocular infection or inflammation Uncontrolled glaucoma Neovascularization of the iris or neovascular glaucoma History of treatment with any anti-angiogenic drugs For study eye: Atrophy or fibrosis involving the center of the fovea at the time of screening or baseline. Cataract (if causing significant visual impairment), planned cataract surgery during the study period, vitrectomy, aphakia, glaucoma surgery, severe vitreous hemorrhage, rhegmatogenous retinal detachment, proliferative retinopathy or choroidal neovascularization of any other cause than wAMD Irreversible structural damage within 0.5 disc diameter of the center of the macula Any intraocular procedure (including cataract surgery, Yttrium-Aluminum-Garnet capsulotomy) within 3 months prior to baseline or anticipated within the next 6 months following baseline. Use of intravitreal or topical ocular corticosteroids administered for at least 30 consecutive days within 3 months prior to screening. For fellow eye - Retinal or choroidal neovascularization or macula edema of any cause Other protocol-defined inclusion/exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Koeln

ZIP/Postal Code

50924

Country

Germany

Facility Name

Novartis Investigative Site

City

Marburg

ZIP/Postal Code

35039

Country

Germany

Facility Name

Novartis Investigative Site

City

München

ZIP/Postal Code

80336

Country

Germany

Facility Name

Novartis Investigative Site

City

München

ZIP/Postal Code

81675

Country

Germany

Facility Name

Novartis Investigative Site

City

Osnabrück

ZIP/Postal Code

49076

Country

Germany

Facility Name

Novartis Investigative Site

City

Regensburg

ZIP/Postal Code

93042

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Systemic Vascular Endothelial Growth Factor (VEGF) Protein Dynamics Following Intravitreal Injections of Ranibizumab Versus Aflibercept in Patients With Neovascular Age-related Macular Degeneration

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