Efficacy and Safety of Ranibizumab in Two "Treat and Extend" Treatment Algorithms Versus Ranibizumab As Needed in Patients With Macular Edema and Visual Impairment Secondary to Diabetes Mellitus

NCT01171976 | Completed Phase 3 Results

• 2 other identifiers: CRFB002D23042010-019795-74
• Study Type: interventional
• Target: 373
• Locations: 13 countries
• Sites: 68

Brief Summary

The purpose of this study is to demonstrate that two investigational treatment regimens have the potential to result in a superior visual acuity improvement as compared to a ranibizumab pro re nata (PRN=as needed) treatment regimen.

Conditions

Diabetic Macular Edema

Keywords

DME; Diabetic macula edema; RETAIN; ranibizumab

Outcome Measures

Primary Outcomes (1)

• Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12

  Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.

  Baseline to Month 12

Secondary Outcomes (9)

• Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24

  Baseline to Month 24

• Visual Acuity of the Study Eye: Change From Baseline at Month 12

  Baseline and Month 12

• Visual Acuity of the Study Eye: Change From Baseline at Month 24

  Baseline and Month 24

• Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12

  Baseline, Month 12

• Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24

  Baseline, 24 month

Study Arms (3)

TE Ranibizumab 0.5 mg and Laser

EXPERIMENTAL

On Day 1, all patients received an intravitreal injection with 0.5 mg ranibizumab and subsequently entered Phase A which comprised of monthly injections. Laser therapy was applied at Day 1. It could then be re-administered according to ETDRS criteria at any visit with 0.5 mg ranibizumab treatment if deemed necessary by the Treating Investigator with a minimal treatment interval between laser treatments of 3 months. Laser therapy was administered ≥ 30 minutes prior to the ranibizumab injection.

Drug: Ranibizumab

TE Ranibizumab 0.5 mg alone

EXPERIMENTAL

Patients received ranibizumab intravitreal injection therapy only.

Drug: Ranibizumab

PRN Ranibizumab 0.5 mg

ACTIVE COMPARATOR

Patients received ranibizumab intravitreal injection therapy as needed according to signs and symptoms of disease.

Drug: Ranibizumab

Interventions

Ranibizumab DRUG

Ranibizumab (Lucentis®) was supplied in vials containing a dose of 0.5 mg/0.05 mL in an aqueous solution (pH 5.5) with histidine, trehalose, and polysorbate 20.

PRN Ranibizumab 0.5 mg; TE Ranibizumab 0.5 mg alone; TE Ranibizumab 0.5 mg and Laser

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient
• Patients with Type 1 or Type 2 diabetes mellitus (according to American Diabetes Association or World Health Organization \[WHO\] guidelines) with glycosylated hemoglobin (HbA1c) ≤ 12.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes. Treatment for diabetes must have been stable for at least 3 month.
• Ocular
• Patients with visual impairment due to DME in at least one eye who are eligible for laser treatment in the opinion of the investigator. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected by the investigator as the study eye.
• BCVA ≥ 39 and ≤78 letters in the study eye and, inclusively, using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/160) at screening.
• Concomitant conditions in the study eye are only permitted if, in the opinion of the investigator, they do not prevent improvement of visual acuity on study treatment.

You may not qualify if:

• Patient Compliance/ Administrative
• Pregnant or nursing (lactating) women.
• Ocular medical history
• Active intraocular inflammation (grade trace or above) in either eye at enrollment.
• Any active infection (e.g. conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) in either eye at the time of enrollment.
• History of uveitis in either eye at any time.
• Structural damage within 0.5 disc diameter of the center of the macular in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema.
• Uncontrolled glaucoma in either eye at screening.
• Prior Ocular treatments
• Panretinal laser photocoagulation in the study eye within 6 months prior to randomization.
• Focal/grid laser photocoagulation in the study eye within 3 months prior to randomization.
• Treatment with anti-angiogenic drugs in either eye.
• Systemic conditions or treatments
• History of stroke within 6 months prior to enrollment.
• Renal failure requiring dialysis.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (68)

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Kortrijk, 8500, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Prague, Czech Republic, 169 02, Czechia

Location

Novartis Investigative Site

Hradec Králové, 505 05, Czechia

Location

Novartis Investigative Site

Olomouc, 775 20, Czechia

Location

Novartis Investigative Site

Pilsen, 301 00, Czechia

Location

Novartis Investigative Site

Prague, 128 08, Czechia

Location

Novartis Investigative Site

Bordeaux, 33 000, France

Location

Novartis Investigative Site

Dijon, 21034, France

Location

Novartis Investigative Site

Lille, 59 037, France

Location

Novartis Investigative Site

Limoges, 87042, France

Location

Novartis Investigative Site

Lyon, 69003, France

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Nice, 6 000, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Paris, 75475, France

Location

Novartis Investigative Site

Heraklion Crete, Crete, GR-71110, Greece

Location

Novartis Investigative Site

Athens, 152 31, Greece

Location

Novartis Investigative Site

Thessaloniki, 546 36, Greece

Location

Novartis Investigative Site

Budapest, 1083, Hungary

Location

Novartis Investigative Site

Budapest, 1133, Hungary

Location

Novartis Investigative Site

Debrecen, 4012, Hungary

Location

Novartis Investigative Site

Győr, 9024, Hungary

Location

Novartis Investigative Site

Dublin, Ireland, Ireland

Location

Novartis Investigative Site

Dublin, Ireland

Location

Novartis Investigative Site

Kilkenny, Ireland

Location

Novartis Investigative Site

Limerick, Ireland

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Milan, MI, 20157, Italy

Location

Novartis Investigative Site

Roma, RM, 00133, Italy

Location

Novartis Investigative Site

Roma, RM, 00198, Italy

Location

Novartis Investigative Site

Leiden 2333 ZA, Netherlands, 2333, Netherlands

Location

Novartis Investigative Site

Amsterdam, 1081 HV, Netherlands

Location

Novartis Investigative Site

Amsterdam, 1105 AZ, Netherlands

Location

Novartis Investigative Site

Nijmegen, 6525 EX, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3011 BH, Netherlands

Location

Novartis Investigative Site

Bielsko-Biala, 43-300, Poland

Location

Novartis Investigative Site

Lublin, 20-954, Poland

Location

Novartis Investigative Site

Warsaw, 00-416, Poland

Location

Novartis Investigative Site

Wroclaw, 50-367, Poland

Location

Novartis Investigative Site

Porto, Portugal, 4099-001, Portugal

Location

Novartis Investigative Site

Coimbra, 3000-354, Portugal

Location

Novartis Investigative Site

Lisbon, 1150-199, Portugal

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Valladolid, Castille and León, 47011, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15705, Spain

Location

Novartis Investigative Site

Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, 35016, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28040, Spain

Location

Novartis Investigative Site

Alicante, Valencia, 03016, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46015, Spain

Location

Novartis Investigative Site

Zurich, Switzerland, 8063, Switzerland

Location

Novartis Investigative Site

Bern, 3010, Switzerland

Location

Novartis Investigative Site

Bern, 3012, Switzerland

Location

Novartis Investigative Site

Binningen, 4102, Switzerland

Location

Novartis Investigative Site

Frimley, Surrey, GU16 7UJ, United Kingdom

Location

Novartis Investigative Site

Aberdeen, AB25 2ZN, United Kingdom

Location

Novartis Investigative Site

Bristol, BS1 2LX, United Kingdom

Location

Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

Location

Novartis Investigative Site

Manchester, M13 9WL, United Kingdom

Location

Novartis Investigative Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Novartis Investigative Site

Sheffield, S10 2JF, United Kingdom

Location

Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

Location

Novartis Investigative Site

Sunderland, SR2 9HP, United Kingdom

Location

Novartis Investigative Site

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Publications (1)

• Prunte C, Fajnkuchen F, Mahmood S, Ricci F, Hatz K, Studnicka J, Bezlyak V, Parikh S, Stubbings WJ, Wenzel A, Figueira J; RETAIN Study Group. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Br J Ophthalmol. 2016 Jun;100(6):787-95. doi: 10.1136/bjophthalmol-2015-307249. Epub 2015 Oct 9.

  PMID: 26453639 DERIVED

MeSH Terms

Interventions

Ranibizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2010
• First Posted: July 29, 2010
• Study Start: September 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: September 15, 2014
• Results First Posted: September 15, 2014

Record last verified: 2014-09

Locations

HU (4); GB (10); FR (9); ES (8); BE (3); CZ (5); IT (6); NL (5); PL (4); PT (3); CH (4); IE (4); GR (3)