A Study of the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema

NCT03481660 | Completed Phase 3 Results DMC

• 2 other identifiers: CRTH258B23022017-003960-11
• Study Type: interventional
• Target: 360
• Locations: 23 countries
• Sites: 78

Brief Summary

This was a Phase III, randomized, double-masked, multi-center, active-controlled, two-arm study designed to evaluate the efficacy and safety of brolucizumab 6 mg compared to the active control, aflibercept 2 mg used per authorized label, in subjects with visual impairment due to diabetic macular edema (DME).

Conditions

Diabetic Macular Edema

Keywords

Diabetic Macular Edema; intravitreal injection; brolucizumab; aflibercept; double-masked

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52 for the Study Eye

  Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  Baseline, Week 52

Secondary Outcomes (50)

• Average Mean Change From Baseline in BCVA Over the Period Week 40 Through Week 52 for the Study Eye

  Baseline, period Week 40 through Week 52

• (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 and up to q12w/q16w up to Week 100.

  Week 52, Week 100

• (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 Within Those Patients That Qualified for q12w at Week 36

  Week 36, Week 52

• (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w/q16w up to Week 100, Within Those Patients That Qualified for q12w at Week 36

  Week 36, Week 100

• (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained on q16w up to Week 100 Within the Patients on q12w at Week 68 and on q16w at Week 76

  Week 68, Week 76, Week 100

Study Arms (2)

Brolucizumab 6 mg

EXPERIMENTAL

Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule

Drug: Brolucizumab

Aflibercept 2 mg

ACTIVE COMPARATOR

Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks

Drug: Aflibercept

Interventions

Brolucizumab DRUG

Intravitreal injection

Also known as: RTH258, ESBA1008

Brolucizumab 6 mg

Aflibercept DRUG

Intravitreal injection

Also known as: Eylea

Aflibercept 2 mg

Eligibility Criteria

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

You may qualify if:

• General
• Patients must give written informed consent before any study related assessments are performed
• Patients with type 1 or type 2 diabetes mellitus and HbA1c of =\< 10% at screening
• Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain stable during the course of the study
• Study Eye
• Visual impairment due to DME with:
• BCVA score between 78 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/320), at screening and baseline
• DME involving the center of the macula, with central subfield retinal thickness (measured from RPE to ILM inclusively) of \>= 320 micrometers (μm) on SD-OCT at screening If both eyes are eligible, the eye with the worse visual acuity will be selected for study eye. However, the investigator may select the eye with better visual acuity, based on medical reasons or local ethical requirements.

You may not qualify if:

• Previous treatment with any anti-VEGF drugs or investigational drugs in the study eye
• Active proliferative diabetic retinopathy in the study eye as per the investigator
• Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g., cataract, vitreous hemorrhage, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause)
• Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
• Structural damage of the fovea in the study eye at screening likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques
• Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) \> 25 millimeters mercury (mmHg) on medication or according to investigator's judgment, at screening or baseline
• Neovascularization of the iris in the study eye at screening or baseline
• Evidence of vitreomacular traction in the study eye at screening or baseline which, in the opinion of the investigator, affect visual acuity

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (78)

Novartis Investigative Site

Alken, 3570, Belgium

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Novartis Investigative Site

Sofia, 1606, Bulgaria

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Sofia, 1784, Bulgaria

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Varna, 9000, Bulgaria

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Hradec Králové, CZE, 500 05, Czechia

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Prague, 100 34, Czechia

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Prague, 12808, Czechia

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Aalborg, 9000, Denmark

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Roskilde, 4000, Denmark

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Tallinn, 11412, Estonia

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Tartu, 51014, Estonia

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Lyon, Rhone, 69317, France

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Bobigny, 93009, France

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Bordeaux, 33000, France

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Créteil, 94000, France

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Dijon, 21034, France

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Lyon, 69275, France

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Marseille, F 13008, France

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Montauban, 82000, France

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Nantes, 44093, France

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Paris, 75010, France

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Paris, 75015, France

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Rouen, 76100, France

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Berlin, 10713, Germany

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Düsseldorf, 40212, Germany

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Freiburg im Breisgau, 79106, Germany

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Göttingen, 37075, Germany

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Leipzig, 04103, Germany

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Münster, 48145, Germany

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Ulm, 89075, Germany

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Budapest, H-1083, Hungary

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Debrecen, 4032, Hungary

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Nyíregyháza, 4400, Hungary

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Szeged, H 6725, Hungary

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Szombathely, H-9700, Hungary

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Chennai, Tamil Nadu, 600006, India

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Coimbatore, Tamil Nadu, 641014, India

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Hyderabad, Telangana, 500 034, India

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Chandigarh, 160012, India

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New Delhi, 110029, India

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Riga, LV 1002, Latvia

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Beirut, 116-5311, Lebanon

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Beirut, 70-933, Lebanon

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Novartis Investigative Site

El Achrafiyé, 166830, Lebanon

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Kaunas, LTU, LT 50161, Lithuania

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Vilnius, LT-08661, Lithuania

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Petaling Jaya, Selangor, 46150, Malaysia

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Shah Alam, Selangor, 40000, Malaysia

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Oslo, NO-0407, Norway

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Gdansk, 80 809, Poland

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Cheboksary, 428028, Russia

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Kazan', 420066, Russia

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Novartis Investigative Site

Moscow, 119021, Russia

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Moscow, 127486, Russia

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Yekaterinburg, 620109, Russia

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Singapore, 168751, Singapore

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Singapore, S308433, Singapore

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Banská Bystrica, 975 17, Slovakia

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Bratislava, 82606, Slovakia

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Novartis Investigative Site

Bratislava, 83301, Slovakia

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Poprad, 05845, Slovakia

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Novartis Investigative Site

Trenčín, 91101, Slovakia

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Novartis Investigative Site

Bundang Gu, Gyeonggi-do, 13620, South Korea

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Novartis Investigative Site

Busan, 49241, South Korea

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Seoul, 02841, South Korea

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Seoul, 05505, South Korea

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Novartis Investigative Site

Seoul, 06351, South Korea

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Novartis Investigative Site

Seoul, 07301, South Korea

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Örebro, 701 85, Sweden

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Bern, 3007, Switzerland

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Zurich, 8063, Switzerland

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Novartis Investigative Site

Changhua, 50006, Taiwan

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Novartis Investigative Site

Taichung, 40447, Taiwan

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Novartis Investigative Site

Taoyuan District, 33305, Taiwan

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Novartis Investigative Site

Ankara, 06230, Turkey (Türkiye)

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Novartis Investigative Site

Gaziantep, 27310, Turkey (Türkiye)

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Novartis Investigative Site

Izmir, 35340, Turkey (Türkiye)

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Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

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MeSH Terms

Interventions

brolucizumab; aflibercept

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2018
• First Posted: March 29, 2018
• Study Start: July 27, 2018
• Primary Completion: June 29, 2020
• Study Completion: June 8, 2021
• Last Updated: January 7, 2025
• Results First Posted: January 5, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

KR (6); SE (1); PL (1); FR (12); CZ (3); ES (2); LI (2); LE (3); RU (5); SG (2); IN (5); DE (7); BU (3); DK (2); BE (1); SL (5); TW (3); TU (4); CH (2); LA (1); MY (2); NO (1); HU (5)