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

NCT03917472 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CRTH258B23052019-001004-37
• Study Type: interventional
• Target: 517
• Locations: 5 countries
• Sites: 92

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of brolucizumab vs. aflibercept in the treatment of patients with visual impairment due to diabetic macular edema (DME).

Conditions

Diabetic Macular Edema

Keywords

Diabetic Macular Edema; intravitreal injection; brolucizumab; aflibercept; double-masked; Diabetic Macular edema (DME); macular edema; diabetic retinopathy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52

  BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/40 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.

  Baseline, Week 52

Secondary Outcomes (14)

• Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit

  Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

• Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit

  Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

• Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye

  Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

• Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit

  Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

• Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit

  Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

Study Arms (2)

Brolucizumab 6mg q4w

EXPERIMENTAL

Brolucizumab 6 mg/0.05 mL every 4 weeks.

Drug: Brolucizumab

Aflibercept 2mg q4w

ACTIVE COMPARATOR

Aflibercept 2mg/0.05 mL every 4 weeks

Drug: Aflibercept

Interventions

Brolucizumab DRUG

Intravitreal injection

Also known as: RTH258, ESBA1008

Brolucizumab 6mg q4w

Aflibercept DRUG

Intravitreal injection

Also known as: Eylea

Aflibercept 2mg q4w

Eligibility Criteria

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

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study.
• Patients with type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) ≤ 12% at screening.
• Study eye: Visual impairment due to DME with:
• Best-corrected visual acuity (BCVA) score between 73 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters
• DME involving the center of the macula, with Central Subfield Thickness (CSFT) ≥ 320 µm on Spectral Domain Optical Coherence Tomography (SD-OCT)

You may not qualify if:

• High-risk proliferative diabetic retinopathy (PDR) in the study eye
• Concomitant conditions or ocular disorders in the study eye which confound interpretation of study results, compromise visual acuity or require medical or surgical intervention
• Any active intraocular or periocular infection or active intraocular inflammation in the either eye
• Uncontrolled glaucoma in the study eye
• Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA \<20/200
• Use of anti-VEGF therapies, intraocular surgery or laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to baseline
• Use of intraocular or periocular corticosteroids in the study eye during the 6-month period prior to baseline, and use of fluocinolone acetonide intravitreal (IVT) implant (Iluvien) at any time prior to baseline
• Prior investigational drugs in either eye, vitreoretinal surgery in the study eye at any time prior to baseline

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (92)

Novartis Investigative Site

Phoenix, Arizona, 85016, United States

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Phoenix, Arizona, 85053, United States

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Tucson, Arizona, 85704-5614, United States

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Beverly Hills, California, 90211, United States

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Campbell, California, 95008, United States

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Fresno, California, 93720, United States

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Huntington Beach, California, 92647, United States

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Loma Linda, California, 92354, United States

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Mountain View, California, 94040, United States

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Oakland, California, 94609, United States

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Pasadena, California, 91107, United States

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Poway, California, 92064, United States

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Rancho Cordova, California, 95670, United States

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Redlands, California, 92374, United States

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Riverside, California, 92505, United States

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Sacramento, California, 95817, United States

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Sacramento, California, 95841, United States

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San Francisco, California, 94107, United States

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Santa Ana, California, 92705, United States

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Santa Barbara, California, 93103, United States

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Torrance, California, 90509-2910, United States

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Ventura, California, 93003, United States

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Altamonte Springs, Florida, 32701, United States

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Deerfield Beach, Florida, 33064, United States

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Fort Lauderdale, Florida, 33309, United States

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Fort Myers, Florida, 33912-7125, United States

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Orlando, Florida, 32804, United States

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Pinellas Park, Florida, 33782, United States

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St. Petersburg, Florida, 33711, United States

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Tampa, Florida, 33609, United States

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Atlanta, Georgia, 30342, United States

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Marietta, Georgia, 30060, United States

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‘Aiea, Hawaii, 96701, United States

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Bloomington, Illinois, 61704, United States

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Oak Forest, Illinois, 60452, United States

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Springfield, Illinois, 62704, United States

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Indianapolis, Indiana, 46280, United States

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New Albany, Indiana, 47150, United States

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West Des Moines, Iowa, 50266, United States

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Leawood, Kansas, 66211, United States

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Lenexa, Kansas, 66215, United States

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Hagerstown, Maryland, 21740, United States

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Boston, Massachusetts, 02114, United States

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Royal Oak, Michigan, 48073, United States

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Minneapolis, Minnesota, 55435, United States

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Kansas City, Missouri, 64133, United States

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Reno, Nevada, 89502, United States

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Bloomfield, New Jersey, 07003, United States

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Teaneck, New Jersey, 07666, United States

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Rochester, New York, 14620, United States

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Hickory, North Carolina, 28602, United States

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Southern Pines, North Carolina, 28387, United States

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Cleveland, Ohio, 44122, United States

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Columbus, Ohio, 43210, United States

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Dublin, Ohio, 43016, United States

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Eugene, Oregon, 97401, United States

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Kingston, Pennsylvania, 95403, United States

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Chattanooga, Tennessee, 37421, United States

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Germantown, Tennessee, 38138, United States

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Abilene, Texas, 79606, United States

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Austin, Texas, 78705, United States

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Austin, Texas, 78731, United States

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Austin, Texas, 78750, United States

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Bellaire, Texas, 77401, United States

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Dallas, Texas, 75231, United States

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Fort Worth, Texas, 76104, United States

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Harlingen, Texas, 78550, United States

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Houston, Texas, 77025, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78240, United States

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Southlake, Texas, 76092, United States

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Norfolk, Virginia, 23502, United States

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Morgantown, West Virginia, 26506, United States

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Madison, Wisconsin, 53705-3611, United States

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Pécs, Baranya, 7621, Hungary

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Zalaegerszeg, Zala County, 8900, Hungary

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Budapest, 1083, Hungary

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Debrecen, 4032, Hungary

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Szeged, H 6725, Hungary

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Haifa, 3339419, Israel

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Haifa, 3436212, Israel

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Kfar Saba, 4428164, Israel

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Petah Tikva, 4941492, Israel

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Tel Aviv, 6789140, Israel

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Arecibo, 00612, Puerto Rico

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Banská Bystrica, 97517, Slovakia

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Bratislava, 82606, Slovakia

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Novartis Investigative Site

Bratislava, 85107, Slovakia

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Novartis Investigative Site

Poprad, 058 45, Slovakia

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Novartis Investigative Site

Trebišov, 075 01, Slovakia

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Novartis Investigative Site

Trenčín, 91171, Slovakia

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Novartis Investigative Site

Zvolen, 960 01, Slovakia

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Related Publications (1)

• Singh RP, Barakat MR, Ip MS, Wykoff CC, Eichenbaum DA, Joshi S, Warrow D, Sheth VS, Stefanickova J, Kim YS, He F, Cho GE, Wang Y, Emanuelli A. Efficacy and Safety of Brolucizumab for Diabetic Macular Edema: The KINGFISHER Randomized Clinical Trial. JAMA Ophthalmol. 2023 Dec 1;141(12):1152-1160. doi: 10.1001/jamaophthalmol.2023.5248.

  PMID: 37971723 DERIVED

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Macular Edema; Diabetic Retinopathy

Interventions

brolucizumab; aflibercept

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A masked evaluating investigator will be responsible for all aspects of the study except the injections and the safety assessment following the injections. An unmasked treating investigator was to perform the injections and assess patient safety following the injections.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2019
• First Posted: April 17, 2019
• Study Start: July 17, 2019
• Primary Completion: March 24, 2021
• Study Completion: March 24, 2021
• Last Updated: August 12, 2022
• Results First Posted: April 21, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share

Locations

SL (7); IL (5); HU (5); PR (1); US (74)