Multicenter randomized open-label three-arms controlled 12 months clinical proof of concept study to evaluate efficacy and safety of Ranibizumab alone or in combination with laser treatment vs. laser treatment alone in Proliferative Diabetic Retinopathy

• Register: EUCTR
• Last refreshed on: 22 January 2018
• Main ID: EUCTR2011-005542-35-DE
• Date of registration: 06/03/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: Multicenter randomized open-label three-arms controlled 12 months clinical proof of concept study to evaluate efficacy and safety of Ranibizumab alone or in combination with laser treatment vs. laser treatment alone in Proliferative Diabetic Retinopathy
• Scientific title: Multicenter randomized open-label three-arms controlled 12 months clinical proof of concept study to evaluate efficacy and safety of Ranibizumab alone or in combination with laser photocoagulation vs. laser photocoagulation alone in Proliferative Diabetic Retinopathy - PRIDE
• Date of first enrolment: 08/05/2012
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005542-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Reading Center will be blinded according to treatment group.; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Panretinal laser photocoagulation; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. PDR defined by DRS (Wilkinson et al, 2003). Upon dilated ophthalmoscopy:
-Neovascularization of the disc (NVD) and/or Neovascularization elsewhere (NVE) with or without additional hemorrhage
2. BCVA in study eye at least 20 ETDRS letters (20/400)
3. Type 1 or type 2 diabetes under medical surveillance / with stabilized treatment
4. HBA1c = 12% (=107 mmol/mol)
5. Patients age = 18 willing and able to give written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
1. Proliferative vitreoretinopathy in study eye
2. Clinically significant macular edema (CSME) (according to ETDRS guidelines) with loss of foveal depression assessed by ophthalmoscopy and OCT in study eye
3. Clinically non significant macular edema (CNSME) that is likely to develop the stage of CSME with loss of foveal depression (according to ETDRS guidelines) within study period in study eye
4. Neovascularizations covering an area of = 2 disc areas within the macula (defined as area with 6mm diameter centered on the fovea), originating either from neovascularization of the disc or multiple neovascularizations elsewhere
in study eye
5. Vitreous hemorrhage that impairs adequate judgment of neovascularization by investigator or vitreous hemorrhage that makes adequate treatment with laser or ranibizumab impossible in either eye
6. Vitreomacular traction either seen on clinical examination or OCT with loss of foveal depression in study eye
7. Evidence of severe vitreoretinal interface disease (e.g. epiretinal membrane), either on clinical examination or OCT in study eye
8. Severe ischemic maculopathy in study eye
9. Rubeosis iridis in either eye
10. Uncontrolled glaucoma in either eye (e.g. IOP > 24 mmHg on medications or according to investigator’s judgment)
11. Patients who are monocular or have a BCVA score in the non-study eye (fellow eye) = 20 letters (approximate Snellen equivalent of 20/400) at Visit 1
12. Patients with active or suspected ocular or periocular infections and patients with active intraocular inflammation in study eye
13. Ocular disorders in the study eye that may confound interpretation of study results, compromise visual acuity or, according to the investigator, require medical or surgical intervention during the 12-month core study period in the opinion of the investigator, including cataract, retinal vascular occlusion, retinal detachment, macular hole, macular scars, or choroidal neovascularisation (e.g., AMD, ocular histoplasmosis, or pathologic myopia)
14. Presence of a substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e. a 20/40 cataract) or is likely to progress within core study period in study eye
15. Previous treatment with PRP in study eye with more than 300 laser spots. Last PRP session within 6 months prior randomization
16. Last laser treatment for DME less than 3 months ahead of baseline visit in study eye
17. Vitrectomy/vitreoretinal surgery
a. in the medical history or planned for study eye
b. planned vitrectomy or vitrectomy in last 3 months for fellow eye
18. Anti-angiogenic drugs in study eye within 3 months prior randomization
19. Prior application of corticosteroid (incl. corticosteroid releasing implant, e.g. Ozurdex®) in vitreous in study eye within 6 months prior to randomization. Prior application of fluocinolonacetonid releasing implant (Iluvien®) in vitreous in study eye within 36 months prior randomization.
20. History of intravitreal corticosteroids in phakic study eye
21. Surgery (e.g. cataract surgery) within last 3 months prior randomization in study eye
(...)
30. Study eyes, who have already been randomized into this trial earlier and received medication must not be included a second time
31. Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism or drug abuse, personality disorder or use of major tranquilizers,

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Proliferative diabetic retinopathy
MedDRA version: 18.1 Level: LLT Classification code 10036857 Term: Proliferative diabetic retinopathy System Organ Class: 100000004853

Intervention(s)

Trade Name: Lucentis
Product Name: Ranibizumab
Product Code: RFB002
Pharmaceutical Form: Solution for injection
INN or Proposed INN: RANIBIZUMAB
CAS Number: 347396-82-1
Current Sponsor code: RFB002
Other descriptive name: not applicable
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Lucentis
Product Name: Lucentis
Product Code: RFB002
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: RANIBIZUMAB
CAS Number: 347396-82-1
Current Sponsor code: RFB002
Other descriptive name: not applicable
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): The primary variable of this study is the area of neovascularisations

Secondary Objective: -BCVA in all patients (ETDRS letters)
-Rates of patients (given as percentages per treatment group)
--with = 5/10/15 ETDRS letters gain
--with no clinical relevant change (less than 5 letters gain or loss, “stable visual acuity”)
--with = 5/10/15 ETDRS letters loss
--with improvement in BCVA (ETDRS letters)
-Change in classification of DR based on the ETDRS severity scale (assessed by FP)
-Change in retinal thickness (OCT) and further anatomic outcomes
-Number of treatments
-Safety
-Change of area of neovascularization (assessed by FLA) at month 3
-Safety
-Change of area of neovascularization (assessed by FLA) at month 3

Main Objective: Change of area of neovascularizations as measured by Fluorescein Angiography at month 12 (difference to baseline value).

Timepoint(s) of evaluation of this end point: Month 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: month 3 and month 12

Secondary end point(s): All quantitative secondary outcomes (i.e. BCVA, CRT) will be analyzed with ANCOVA models analogous to the primary endpoint. For the binary secondary endpoints (VA gain/loss >= 15/10 letters), the absolute and relative frequencies will be tabulated. For treatment comparisons, the difference in proportions and the Odds ratio will be calculated with the respective confidence intervals and p-values.

Secondary ID(s)

CRFB002DDE21

Source(s) of Monetary Support

Novartis Pharma GmbH