Clinical trial NCT04278417: Study of Efficacy and Safety of Brolucizumab Versus Panretinal Photocoagulation Laser in Patients With Proliferative Diabetic Retinopathy
Official title: A 96-week, Two-arm, Randomized, Single-masked, Multi-center, Phase III Study Assessing the Efficacy and Safety of Brolucizumab 6 mg Compared to Panretinal Photocoagulation Laser in Patients With Proliferative Diabetic Retinopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Proliferative Diabetic Retinopathy
Keywords: proliferative diabetic retinophathy, retinal neovascularization, anti-VEGF, brolucizumab, intravitreal injection, panretinal photocoagulation
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-02-20
Enrollment: 689
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of brolucizumab compared to panretinal photocoagulation laser (PRP) in patients with proliferative diabetic retinopathy (PDR). This evaluation will provide information that brolucizumab is non-inferior to PRP with respect to the change in best corrected visual acuity at Week 54.

Detailed description: The study is an ongoing, Phase III, 96-week, two-arm, randomized (1:1 ratio), single-masked, multi-center, active-controlled study to evaluate the efficacy and safety of brolucizumab compared to Panretinal photocoagulation (PRP) in subjects with Proliferative diabetic retinopathy (PDR). Subjects who met all the inclusion and none of the exclusion criteria were randomized in a 1:1 ratio to one of the following treatments:

* Brolucizumab 6 mg: 3 x q6w loading then q12w maintenance through Week 90, with the option from Week 48 onwards to extend the treatment interval by 6 weeks at a time up to 24 weeks and revert to q12w if disease worsens. More frequent injection with q6w interval in the maintenance phase could be administered at the discretion of the Investigator if the disease worsens.
* PRP: initial treatment in 1-4 sessions up to Week 12, followed with additional PRP treatment (may split into 2-4 sessions) as needed up to Week 90. Visits occurred every 6 weeks throughout the study, regardless of treatment or not.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent must be obtained prior to participation
* Able to complete adequate fundus photographs and retinal images
* Diagnosis of type 1 or 2 Diabetes Mellitus (DM) and HbA1c less than or equal to 12% at screening
* DM treatment stable for at least 3 months
* PDR diagnosis with no previous PRP treatment in the study eye

Exclusion Criteria:

* Concomitant conditions or ocular disorders in the study eye at Screening or Baseline that could compromise a response to study treatment.
* Presence of diabetic macular edema in the study eye
* Active infection or inflammation in the study eye
* Uncontrolled glaucoma (IOP greater than 25 mmHg)
* Intravitreal anti-VEGF treatment within 6 months
* Treatment with intraocular corticosteroids
* End stage renal disease requiring dialysis or kidney transplant
* Uncontrolled blood pressure
* Systemic anti-VEGF therapy at any time

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 54
timeFrame: Baseline, Week 54
Secondary outcomes:
measure: Number and Percentage of Subjects With no Proliferative Diabetic Retinopathy (PDR) at Week 54
timeFrame: Week 54
measure: Number and Percentage of Subjects With Center-involved Diabetic Macular Edema (CI- DME) up to Week 54
timeFrame: Up to Week 54
measure: Area Under the Curve in Change From Baseline in BCVA up to Week 54
timeFrame: From Baseline, up to Week 54
measure: Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥2 Steps Improvement From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54
timeFrame: Baseline, Week 54
measure: Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥2 Steps Worsening From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 18 and Week 54
timeFrame: Baseline, Week 18, and Week 54
measure: Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥3 Steps Improvement From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 54
timeFrame: Baseline and Week 54
measure: Diabetic Retinopathy Severity Scale (DRSS): Number and Percentage of Subjects With ≥3 Steps Worsening From Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) DRSS Score at Week 18 and Week 54
timeFrame: Baseline, Week 18, and Week 54
measure: Number and Percentage of Subjects Developing Vision-threatening Complications Associated With Diabetic Retinopathy up to Week 54
timeFrame: Up to Week 54
measure: Ocular AEs (>= 2% in Any Treatment Arm) by Preferred Term for the Study Eye
timeFrame: AEs are reported from first dose of study treatment until the last pt still enrolled at the time of the primary analysis cut-off finished the Week 54 tests (or Day 413 for pts who missed the Week 54 visit but were ongoing.) The study is still ongoing.
measure: Non-ocular AEs (≥ 2% in Any Treatment Arm) by Preferred Term
timeFrame: AEs are reported from first dose of study treatment until the last pt still enrolled at the time of the primary analysis cut-off finished the Week 54 tests (or Day 413 for pts who missed the Week 54 visit but were ongoing.) The study is still ongoing.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Retina Associates SW
state: Arizona
city: Beverly Hills
country: United States
facility: Retina- Vitreous Assoc Medical Group .
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: Huntington Beach
country: United States
facility: Salehi Retina Institute
state: California
city: Redlands
country: United States
facility: Retina Consultants of Southern California .
state: California
city: Torrance
country: United States
facility: Premiere Practice Management LLC
state: California
city: Torrance
country: United States
facility: Lundquist Inst BioMed at Harbor .
state: California
city: Ventura
country: United States
facility: Novartis Investigative Site
state: California
city: Deerfield Beach
country: United States
facility: Advanced Research LLC
state: Florida
city: Deerfield Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Novartis Investigative Site
state: Florida
city: Fort Myers
country: United States
facility: Novartis Investigative Site
state: Florida
city: Jacksonville
country: United States
facility: Florida Retina Institute
state: Florida
city: Lakeland
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute Ophthalmology
state: Florida
city: Panama City
country: United States
facility: Eye Center of North Florida
state: Florida
city: Plantation
country: United States
facility: Novartis Investigative Site
state: Florida
city: Elmhurst
country: United States
facility: Retina Associates
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Eye Institute .
state: Indiana
city: New Albany
country: United States
facility: John-Kenyon American Eye Institute PC
state: Indiana
city: Lenexa
country: United States
facility: Retina Associates PA
state: Kansas
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Jackson
country: United States
facility: University of Mississippi Med Ctr .
state: Mississippi
city: Cleveland
country: United States
facility: Retina Associates Of Cleveland .
state: Ohio
city: Oklahoma City
country: United States
facility: Dean McGee Eye Institute
state: Oklahoma
city: Springfield
country: United States
facility: Cascade Medical Research Institute
state: Oregon
city: Erie
country: United States
facility: Erie Retinal Surgery
state: Pennsylvania
city: Ladson
country: United States
facility: Charleston Neuroscience Institute
state: South Carolina
city: Knoxville
country: United States
facility: Southeastern Retina Associates P C .
state: Tennessee
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: Texan Eye P A
state: Texas
city: Bellaire
country: United States
facility: Novartis Investigative Site
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants TX Rsrch Ctr
state: Texas
city: Fort Worth
country: United States
facility: Texas Retina Associates
state: Texas
city: Harlingen
country: United States
facility: Valley Retina Institute PA .
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Medical Center Opthamology Assoc .
state: Texas
city: San Antonio
country: United States
facility: Retina Associates Of South Texas PA CRFB002H2301
state: Texas
city: Norfolk
country: United States
facility: Virginia Eye Consultants
state: Virginia
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: De Santa Fe
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Albury
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Liverpool
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Parramatta
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Strathfield
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Blumenau
country: Brazil
facility: Novartis Investigative Site
state: SC
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sorocaba
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Boisbriand
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: RM
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Shantou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Nanjing City
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nantong
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Changchun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Shenyang City
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Xian
country: China
facility: Novartis Investigative Site
state: Shaanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Tianjin
country: China
facility: Novartis Investigative Site
state: Tianjin
city: Wenzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Coimbatore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Tirunelveli
country: India
facility: Novartis Investigative Site
state: Tamilnadu
city: Chandigarh
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Nagakute-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Sakura
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Yoshida-gun
country: Japan
facility: Novartis Investigative Site
state: Fukui
city: Kurume city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Koriyama
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Asahikawa
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kita-gun
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Tsu-city
country: Japan
facility: Novartis Investigative Site
state: Mie
city: Matsumoto
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Shimotsuke
country: Japan
facility: Novartis Investigative Site
state: Tochigi
city: Chiyoda-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Hachioji-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Meguro-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Akita
country: Japan
facility: Novartis Investigative Site
city: Kobe-shi
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Bundang Gu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Daegu
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Ciudad De
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Ciudad de Mexico
country: Mexico
facility: Novartis Investigative Site
city: Tijuana
country: Mexico
facility: Novartis Investigative Site
city: Makati
country: Philippines
facility: Novartis Investigative Site
state: NCR
city: Makati
country: Philippines
facility: Novartis Investigative Site
city: Pasig City
country: Philippines
facility: Novartis Investigative Site
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center LLC
city: Cheboksary
country: Russian Federation
facility: Novartis Investigative Site
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Omsk
country: Russian Federation
facility: Novartis Investigative Site
city: Sterlitamak
country: Russian Federation
facility: Novartis Investigative Site
city: Ulyanovsk
country: Russian Federation
facility: Novartis Investigative Site
city: Hualien
country: Taiwan
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: