NCT03481634

Brief Summary

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

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
566

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jul 2018

Typical duration for phase_3

Geographic Reach
13 countries

108 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 13, 2018

Completed
16 days until next milestone

First Posted

Study publicly available on registry

March 29, 2018

Completed
4 months until next milestone

Study Start

First participant enrolled

July 23, 2018

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 11, 2020

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 18, 2021

Completed
1 year until next milestone

Results Posted

Study results publicly available

October 28, 2022

Completed
Last Updated

January 30, 2023

Status Verified

January 1, 2023

Enrollment Period

2.3 years

First QC Date

March 13, 2018

Results QC Date

May 27, 2022

Last Update Submit

January 27, 2023

Conditions

Keywords

Diabetic Macular Edemaintravitreal injectionbrolucizumabafliberceptdouble-maskedDiabetic Macular Edema (DME)macular edemadiabetic retinopathy

Outcome Measures

Primary Outcomes (1)

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

    BCVA was 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 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. This endpoint was analyzed via the pairwise ANOVA method where the 2 dose groups of Brolucizumab are compared to Aflibercept.

    Baseline, Week 52

Secondary Outcomes (33)

  • Average Change From Baseline in BCVA Over the Period Week 40 Through Week 52

    Baseline and Week 40 through Week 52 (average)

  • Patients Maintained at q12w - Probability of Maintaining on q12w

    Baseline (Week 0), Weeks 32, 36 and 48

  • Patients Maintained at q12w (for Those Patients Who Qualified for q12w at Week 36) - Probability of Maintaining on q12w

    Weeks 36 and 48

  • Change From Baseline in BCVA at Each Visit up to Week 52

    Baseline (Week 0), Weeks 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52

  • BCVA (Letters Read): ANOVA Results for Average Change From Baseline Over the Period Week 88 Through Week 100 for the Study Eye (FAS - LOCF)

    Baseline, and Week 88 through Week 100 (average)

  • +28 more secondary outcomes

Study Arms (3)

Brolucizumab 3 mg

EXPERIMENTAL

Brolucizumab 3 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule. To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP).

Drug: Brolucizumab

Brolucizumab 6 mg

EXPERIMENTAL

Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule. To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP).

Drug: Brolucizumab

Aflibercept 2 mg

ACTIVE COMPARATOR

Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks. To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP).

Drug: Aflibercept

Interventions

Intravitreal injection

Also known as: RTH258, ESBA1008
Brolucizumab 3 mgBrolucizumab 6 mg

Intravitreal injection

Also known as: Eylea
Aflibercept 2 mg

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent before any assessment
  • Patients with type 1 or type 2 diabetes mellitus and HbA1c of ≤10% at screening
  • Medication for the management of diabetes stable within 3 months prior to randomization and is expected to remain stable during the course of the study

You may not qualify if:

  • Active proliferative diabetic retinopathy in the study eye
  • Active intraocular or periocular infection or active intraocular inflammation in study eye
  • Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) \> 25 millimeters mercury (mmHg)
  • Previous treatment with anti-VEGF drugs or investigational drugs in the study eye
  • Stroke or myocardial infarction during the 6-month period prior to baseline
  • Uncontrolled blood pressure defined as a systolic value ≥160 mmHg or diastolic value ≥100 mmHg

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (116)

Novartis Investigative Site

Phoenix, Arizona, 85053, United States

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Novartis Investigative Site

Beverly Hills, California, 90211, United States

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Novartis Investigative Site

La Jolla, California, 92093, United States

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Novartis Investigative Site

Mountain View, California, 94040, United States

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Novartis Investigative Site

Santa Barbara, California, 93103, United States

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Novartis Investigative Site

Colorado Springs, Colorado, 80909, United States

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Novartis Investigative Site

Danbury, Connecticut, 06810, United States

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Novartis Investigative Site

Miami, Florida, 33136, United States

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Novartis Investigative Site

Pensacola, Florida, 32503, United States

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Novartis Investigative Site

Stuart, Florida, 34994, United States

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Novartis Investigative Site

‘Aiea, Hawaii, 96701, United States

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Novartis Investigative Site

Urbana, Illinois, 61801, United States

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Novartis Investigative Site

Wheaton, Illinois, 60187, United States

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Novartis Investigative Site

Indianapolis, Indiana, 46280, United States

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Novartis Investigative Site

New Albany, Indiana, 47150, United States

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Novartis Investigative Site

Leawood, Kansas, 66211, United States

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Novartis Investigative Site

Lenexa, Kansas, 66215, United States

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Novartis Investigative Site

Paducah, Kentucky, 42001, United States

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Novartis Investigative Site

Springfield, Massachusetts, 01107, United States

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Novartis Investigative Site

Stoneham, Massachusetts, 02180, United States

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Novartis Investigative Site

Reno, Nevada, 89502, United States

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Novartis Investigative Site

Cincinnati, Ohio, 45242, United States

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Novartis Investigative Site

Cleveland, Ohio, 44122, United States

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Novartis Investigative Site

Cleveland, Ohio, 44195, United States

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Novartis Investigative Site

Kingston, Pennsylvania, 95403, United States

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Novartis Investigative Site

Philadelphia, Pennsylvania, 19107, United States

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Novartis Investigative Site

Memphis, Tennessee, 38119, United States

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Novartis Investigative Site

Nashville, Tennessee, 37232, United States

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Novartis Investigative Site

Austin, Texas, 78705, United States

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Novartis Investigative Site

Austin, Texas, 78731, United States

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Novartis Investigative Site

Austin, Texas, 78750, United States

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Novartis Investigative Site

Bellaire, Texas, 77401, United States

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Novartis Investigative Site

Harlingen, Texas, 78550, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

San Antonio, Texas, 78240, United States

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Novartis Investigative Site

Tyler, Texas, 75701, United States

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Novartis Investigative Site

Silverdale, Washington, 98383, United States

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Novartis Investigative Site

Spokane, Washington, 99204, United States

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Novartis Investigative Site

Madison, Wisconsin, 53705-3611, United States

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Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO, Argentina

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Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

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Novartis Investigative Site

CABA, 1425, Argentina

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Novartis Investigative Site

CABA, Argentina

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Novartis Investigative Site

Córdoba, X5000AAJ, Argentina

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Novartis Investigative Site

Liverpool, New South Wales, 2170, Australia

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Novartis Investigative Site

Parramatta, New South Wales, 2150, Australia

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Novartis Investigative Site

Sydney, New South Wales, 2000, Australia

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Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

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Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

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Novartis Investigative Site

Clayton, Victoria, 3168, Australia

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Novartis Investigative Site

Melbourne, Victoria, 3002, Australia

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Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

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Novartis Investigative Site

Graz, A-8036, Austria

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Novartis Investigative Site

Innsbruck, 6020, Austria

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Novartis Investigative Site

Vienna, 1090, Austria

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Novartis Investigative Site

Ottawa, Ontario, K1Z 8R2, Canada

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Novartis Investigative Site

Toronto, Ontario, M4N 3M5, Canada

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Novartis Investigative Site

Toronto, Ontario, M5C 2T2, Canada

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Novartis Investigative Site

Québec, G1S 4L8, Canada

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Novartis Investigative Site

Medellín, Antioquia, 001, Colombia

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Novartis Investigative Site

Medellín, Antioquia, Colombia

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Novartis Investigative Site

Bogotá, 110221, Colombia

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Novartis Investigative Site

Haifa, 3109601, Israel

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Novartis Investigative Site

Haifa, 3339419, Israel

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Novartis Investigative Site

Haifa, 3436212, Israel

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Novartis Investigative Site

Jerusalem, 9112001, Israel

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Novartis Investigative Site

Kfar Saba, 4428164, Israel

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Novartis Investigative Site

Petah Tikva, 4941492, Israel

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Novartis Investigative Site

Rehovot, 7610001, Israel

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Novartis Investigative Site

Tel Aviv, 6423906, Israel

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Novartis Investigative Site

Chieti, CH, 66100, Italy

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Novartis Investigative Site

Catania, CT, 95124, Italy

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Novartis Investigative Site

Milan, MI, 20100, Italy

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Novartis Investigative Site

Milan, MI, 20132, Italy

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Novartis Investigative Site

Padua, PD, 35128, Italy

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Novartis Investigative Site

Roma, RM, 00144, Italy

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Novartis Investigative Site

Nagoya, Aichi-ken, 455-8530, Japan

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Novartis Investigative Site

Nagoya, Aichi-ken, 457-8511, Japan

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Novartis Investigative Site

Nagoya, Aichi-ken, 462-0825, Japan

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Novartis Investigative Site

Nagoya, Aichi-ken, 466 8560, Japan

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Novartis Investigative Site

Kurume, Fukuoka, 830-8543, Japan

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Novartis Investigative Site

Amagasaki, Hyōgo, 660 8550, Japan

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Novartis Investigative Site

Tsuchiura, Ibaragi, 300-0817, Japan

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Novartis Investigative Site

Ishioka, Ibaraki, 315-0037, Japan

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Novartis Investigative Site

Kagoshima, Kagoshima-ken, 890 8520, Japan

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Novartis Investigative Site

Matsumoto, Nagano, 390-8621, Japan

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Novartis Investigative Site

Saitama-shi, Saitama, 336-0963, Japan

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Novartis Investigative Site

Shimotsuke, Tochigi, 329-0498, Japan

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Novartis Investigative Site

Chiyoda-ku, Tokyo, 101-8309, Japan

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Novartis Investigative Site

Hachiōji, Tokyo, 193-0944, Japan

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Novartis Investigative Site

Shinjuku Ku, Tokyo, 162 8666, Japan

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Novartis Investigative Site

Taito-ku, Tokyo, 111-0051, Japan

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Novartis Investigative Site

Kumamoto, Japan

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Novartis Investigative Site

Osaka, 543-0027, Japan

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Novartis Investigative Site

Amsterdam, 1105 AZ, Netherlands

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Novartis Investigative Site

Rotterdam, 3011 BH, Netherlands

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Novartis Investigative Site

Tilburg, 5022 GC, Netherlands

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Novartis Investigative Site

Coimbra, 3000-548, Portugal

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Novartis Investigative Site

Coimbra, 3030-363, Portugal

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Novartis Investigative Site

Leiria, 2410-187, Portugal

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Novartis Investigative Site

Porto, 4099-001, Portugal

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Novartis Investigative Site

Porto, 4200 319, Portugal

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Novartis Investigative Site

Santa Maria da Feira, 4520 211, Portugal

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Novartis Investigative Site

Vila Franca de Xira, 2600-009, Portugal

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Novartis Investigative Site

Arecibo, 00612, Puerto Rico

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Novartis Investigative Site

Valladolid, Castille and León, 47011, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

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Novartis Investigative Site

Sant Cugat del Vallès, Catalonia, 08190, Spain

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Novartis Investigative Site

Valencia, Valencia, 46014, Spain

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Novartis Investigative Site

Barcelona, 08025, Spain

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Novartis Investigative Site

Zaragoza, 50009, Spain

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Novartis Investigative Site

Frimley, Surrey, GU16 7UJ, United Kingdom

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Novartis Investigative Site

Birmingham, B18 7QH, United Kingdom

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Novartis Investigative Site

Hull, HU3 2JZ, United Kingdom

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Novartis Investigative Site

London, NW10 7NS, United Kingdom

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Novartis Investigative Site

Nottingham, NG7 2UH, United Kingdom

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Related Links

MeSH Terms

Conditions

Macular EdemaDiabetic Retinopathy

Interventions

brolucizumabaflibercept

Condition Hierarchy (Ancestors)

Macular DegenerationRetinal DegenerationRetinal DiseasesEye DiseasesDiabetic AngiopathiesVascular DiseasesCardiovascular DiseasesDiabetes ComplicationsDiabetes MellitusEndocrine System Diseases

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals

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 13, 2018

First Posted

March 29, 2018

Study Start

July 23, 2018

Primary Completion

November 11, 2020

Study Completion

October 18, 2021

Last Updated

January 30, 2023

Results First Posted

October 28, 2022

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will share

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Locations