24 Week Study to Compare Systemic VEGF-levels of Ranibizumab and Aflibercept in DME. (TIDE DME)

April 27, 2017 updated by: Novartis Pharmaceuticals

A 24-week, Randomized, Single-masked, Multicenter, Phase IV Study to Compare sysTemic VEGF Levels Following Monthly Intravitreal Injections of 0.5 mg Ranibizumab Versus 2 mg Aflibercept Until Week 24 in Patients With Visual Impairment DuE to Diabetic Macular Edema (TIDE DME).

The purpose of the study is to compare the effect of intravitreal injections of ranibizumab and aflibercept on systemic VEGF levels in DME patients in a detailed time course.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The purpose of the study is to compare the effect of monthly intravitreal injections of 0.5 mg ranibizumab and 2.0 mg aflibercept on systemic VEGF levels in patients with visual impairment due to DME over a 24 week period. In addition, the study will also assess the effect on systemic VEGF-A levels when patients are switched from aflibercept to ranibizumab.

Study Type

Interventional

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Type 1 or Type 2 diabetes mellitus
  • Visual impairment due to DME
  • BCVA of 78 to 24 (20/32-20/320) ETDRS letters

Exclusion Criteria:

  • Stroke or myocardial infarction less than 3 months prior to screening.
  • Presence of uncontrolled systolic blood pressure or diastolic blood pressure
  • Renal failure requiring dialysis or renal transplant or renal insufficiency
  • Untreated diabetes mellitus
  • Use of any systemic anti-VEGF drugs within 6 months prior to screening.
  • 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, rhegm
  • Irreversible structural damage within 0.5 disc diameter of the center of the macula
  • Panretinal laser photocoagulation within 6 months prior to randomization.
  • Focal/grid laser photocoagulation within 3 months prior to randomization.
  • Any intraocular procedure (including cataract surgery, Yttrium-Aluminum-Garnet capsulotomy) within 3 months prior to baseline or anticipated within the next 6 months following
  • Topical ocular corticosteroids administered for at least 30 consecutive days within 3 months prior to screening.
  • Application of intravitreal corticosteroids in vitreous within 6 months prior to screening. Prior application of fluocinolonacetonid releasing implant in vitreous within 36 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
Monthly intravitreal injections of 0.5 mg ranibizumab for six months
Drug: Ranibizumab
0.5 mg intravitreal injections
Other Names:
  • Lucentis
Experimental: Group 2
Monthly intravitreal injections of 2 mg aflibercept for the initial three months followed by monthly intravitreal injections of 0.5 mg ranibizumab for the next three months.
Drug: Ranibizumab
0.5 mg intravitreal injections
Other Names:
  • Lucentis
Drug: Aflibercept
2 mg intravitreal injections
Other Names:
  • Eylea
Experimental: Group 3
Monthly injections of 2 mg aflibercept for six months
Drug: Aflibercept
2 mg intravitreal injections
Other Names:
  • Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the curve (AUC) of VEGF-A levels from baseline to week 24
Time Frame: baseline to week 24
Systemic VEGF-A levels following monthly intravitreal injections of 0.5 mg ranibizumab versus 2 mg aflibercept (Area under the curve) expressed in pg/ml*days. The AUC will be standardized (=divided) by the individual follow-up time and will be calculated by the trapezoidal rule..
baseline to week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Systemic VEGF-A levels in serum for patients in treatment group 1 and treatment group 2 within specific time points
Time Frame: Day 7, Day 15, Week 4, week 8, week 12, week 14, week 16, week 18, week 20, week 24
To compare systemic VEGF-A levels (pg/ml) in patients switching from monthly 2 mg aflibercept injections for first three months to monthly 0.5 mg ranibizumab (treatment group 2) for the next three months compared to patients treated with monthly 0.5 mg ranibizumab (treatment group 1) for six months at specific time points from week 12 to week 24. The comparison will be performed at specific time points between week 12 and week 24, based on the blood samples collected for visits 10 to 16.
Day 7, Day 15, Week 4, week 8, week 12, week 14, week 16, week 18, week 20, week 24
Mean Systemic VEGF-A levels in serum for patients in treatment group 1 and treatment group 3 within specific time points
Time Frame: Day 7, Day 15, Week 4, week 8, week 12, week 14, week 16, week 18, week 20, week 24
To compare systemic VEGF-A levels (pg/ml) in patients switching from monthly 2 mg aflibercept injections for first three months to monthly 0.5 mg ranibizumab (treatment group 2) for the next three months compared to patients treated with monthly 2 mg aflibercept (treatment group 3) for six months at specific time points from week 12 to week 24. The comparison will be performed at specific time points between week 12 and week 24, based on the blood samples collected for visits 10 to 16.
Day 7, Day 15, Week 4, week 8, week 12, week 14, week 16, week 18, week 20, week 24
Proportion of patients reporting ocular and/or systemic adverse events in all the three treatment groups.
Time Frame: From Baseline to Week 24

To evaluate ocular and systemic safety in all the three treatment groups. Only treatment-emergent AEs will be summarized.

AEs will be summarized by presenting for each treatment group the number and percentage of patients having any AE, having an eye-related AEs, having an AE in each primary system organ class and having each individual AEs based on the preferred term. All other information collected (e.g., severity or relationship to study treatment) will be tabulated and listed as appropriate. Summary tables will also be presented for the subset of AEs suspected to be treatment related.
From Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 1, 2016

Primary Completion (Anticipated)

September 1, 2017

Study Completion (Anticipated)

September 1, 2017

Study Registration Dates

First Submitted

July 22, 2016

First Submitted That Met QC Criteria

August 21, 2016

First Posted (Estimate)

August 25, 2016

Study Record Updates

Last Update Posted (Actual)

April 28, 2017

Last Update Submitted That Met QC Criteria

April 27, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRFB002D2404

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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