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

Primary Purpose

Visual Impairment Due to Diabetic Macular Edema

Status

Withdrawn

Phase

Phase 4

Locations

Study Type

Interventional

Intervention

Ranibizumab

Aflibercept

About this trial

This is an interventional treatment trial for Visual Impairment Due to Diabetic Macular Edema focused on measuring Diabetic Macular Edema.

Eligibility Criteria

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

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Group 1

Group 2

Group 3

Arm Description

Monthly intravitreal injections of 0.5 mg ranibizumab for six months

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.

Monthly injections of 2 mg aflibercept for six months

Outcomes

Primary Outcome Measures

Area under the curve (AUC) of VEGF-A levels from 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..

Secondary Outcome Measures

Mean Systemic VEGF-A levels in serum for patients in treatment group 1 and treatment group 2 within specific time points

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.

Mean Systemic VEGF-A levels in serum for patients in treatment group 1 and treatment group 3 within specific time points

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.

Proportion of patients reporting ocular and/or systemic adverse events in all the three treatment groups.

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.

Full Information

NCT ID

NCT02878681

First Posted

July 22, 2016

Last Updated

April 27, 2017

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02878681

Brief Title

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

Acronym

TIDE DME

Official Title

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).

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Withdrawn

Study Start Date

September 2016 (Anticipated)

Primary Completion Date

September 2017 (Anticipated)

Study Completion Date

September 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

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

Visual Impairment Due to Diabetic Macular Edema

Keywords

Diabetic Macular Edema.

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

Monthly intravitreal injections of 0.5 mg ranibizumab for six months

Arm Title

Group 2

Arm Type

Experimental

Arm Description

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.

Arm Title

Group 3

Arm Type

Experimental

Arm Description

Monthly injections of 2 mg aflibercept for six months

Intervention Type

Drug

Intervention Name(s)

Ranibizumab

Other Intervention Name(s)

Lucentis

Intervention Description

0.5 mg intravitreal injections

Intervention Type

Drug

Intervention Name(s)

Aflibercept

Other Intervention Name(s)

Eylea

Intervention Description

2 mg intravitreal injections

Primary Outcome Measure Information:

Title

Area under the curve (AUC) of VEGF-A levels from baseline to week 24

Description

Time Frame

baseline to week 24

Secondary Outcome Measure Information:

Title

Mean Systemic VEGF-A levels in serum for patients in treatment group 1 and treatment group 2 within specific time points

Description

Time Frame

Day 7, Day 15, Week 4, week 8, week 12, week 14, week 16, week 18, week 20, week 24

Title

Mean Systemic VEGF-A levels in serum for patients in treatment group 1 and treatment group 3 within specific time points

Description

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.

Time Frame

Day 7, Day 15, Week 4, week 8, week 12, week 14, week 16, week 18, week 20, week 24

Title

Proportion of patients reporting ocular and/or systemic adverse events in all the three treatment groups.

Description

Time Frame

From Baseline to Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

12. IPD Sharing Statement

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

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