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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)

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ClinicalTrials.gov Identifier: NCT02257632
Recruitment Status : Completed
First Posted : October 6, 2014
Results First Posted : May 7, 2019
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Wet Age-Related Macular Degeneration Drug: Ranibizumab 0.5 mg Drug: Aflibercept 2 mg Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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
Actual Study Start Date : April 8, 2015
Actual Primary Completion Date : March 20, 2017
Actual Study Completion Date : June 8, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group 1
6 monthly intravitreal injections of 0.5 mg ranibizumab
Drug: Ranibizumab 0.5 mg
Administered as an intravitreal injection
Other Name: Lucentis

Experimental: Group 2
3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab
Drug: Ranibizumab 0.5 mg
Administered as an intravitreal injection
Other Name: Lucentis

Drug: Aflibercept 2 mg
Administered as an intravitreal injection
Other Name: Eylea




Primary Outcome Measures :
  1. Standardized Area Under the Curve (AUC) for VEGF A Levels by SIMOA (Quanterix's Single Molecule Array) Method for the Comparative Phase [ Time Frame: Baseline up to Week 12 visit (Days 1, 2, 8, 15, 29, 43, 57, 71, 85) ]
    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 :
  1. Systemic VEGF-A Protein Levels From Study Week 12 to 24 [ Time Frame: From study week 12 to 24 (Days 85, 99, 113, 127, 141, 155, 169) ]
    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)

  2. Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline) [ Time Frame: From study week 12 to 24 ]
    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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02257632


Locations
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Germany
Novartis Investigative Site
Koeln, Germany, 50924
Novartis Investigative Site
Marburg, Germany, 35039
Novartis Investigative Site
München, Germany, 80336
Novartis Investigative Site
München, Germany, 81675
Novartis Investigative Site
Osnabrück, Germany, 49076
Novartis Investigative Site
Regensburg, Germany, 93042
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] April 27, 2015
Statistical Analysis Plan  [PDF] November 10, 2017


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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02257632    
Other Study ID Numbers: CRFB002ADE27
First Posted: October 6, 2014    Key Record Dates
Results First Posted: May 7, 2019
Last Update Posted: May 7, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents