Back to results

Study Assessing the Efficacy and Safety of a Personalized Monotherapy Regimen of Brolucizumab in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy (PROUD)

Primary Purpose

Macular Polypoidal Choroidal Vasculopathy (PCV)

Status

Recruiting

Phase

Phase 3

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Brolucizumab 6mg

About this trial

This is an interventional treatment trial for Macular Polypoidal Choroidal Vasculopathy (PCV) focused on measuring Neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, anti-vascular endothelial growth factor, brolucizumab, personalized regimen, treat-and-extend, Retina damage, Retinal disease, Vascular disease, Eye disease, blind spot, fluid leak into or under the retina, blood leak into or under the retina, macular polypoidal choroidal vasculopathy (PCV), PCV

Eligibility Criteria

50 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Participants ≥ 50 years of age at Screening. Study eye: Presence of active polypoidal lesions in the macula as shown by Indocyanine green angiography (ICGA) AND presence of serosanguinous maculopathy, i.e., exudative or hemorrhagic features involving the macula on color fundus photography (CFP), Fluorescein angiography (FA) and spectral domain optical coherence tomography (SD-OCT) AND presence of Intraretinal fluid (IRF) or Subretinal fluid (SRF) that affects the central subfield as seen by SD-OCT. Best-corrected visual acuity (BCVA) score must be ≤ 78 and ≥ 24 letters at 4 meters starting distance using early treatment diabetic retinopathy study (ETDRS) visual acuity charts at both Screening and Baseline. Greatest liner dimension (GLD) of the total lesion area (branching vascular network [BVN] + polypoidal lesion) < 5400 μm (equivalent to 9 macular photocoagulation study [MPS] Disc Area) as delineated by Indocyanin green angiography (ICGA). Exclusion Criteria: Ocular conditions: 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 planned medical or surgical intervention during the first 12-month study period. Any active intraocular or periocular infection or active intraocular inflammation (IOI) (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye or fellow eye at Screening or Baseline. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to Investigator's judgment, at Screening or Baseline. Any Polypoidal choroidal vasculopathy (PCV) masquerades like macular aneurysms, macular telangiectasia, etc. in study eye. Total area of subretinal hemorrhage larger than 9 DA (Disc Area) or comprising ≥ 50% of the lesion area or presence of vitreous hemorrhage in study eye. Ocular treatments in the study eye: Previous treatment with any anti-Vascular endothelial growth factor (VEGF) drugs or investigational drugs at any time prior to Baseline. Previous use of intraocular or periocular steroids within the 6-month period prior to Baseline. Macular laser photocoagulation (focal/grid) or Photodynamic therapy (PDT) at any time prior to Baseline and peripheral laser photocoagulation within 3 months prior to Baseline. Systemic conditions or treatments: Stroke or myocardial infarction during the 6-month period prior to Baseline. Systemic anti-VEGF therapy any time prior to Baseline.

Sites / Locations

Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Personalized regimen arm

Standard regimen arm

Arm Description

1~3 x 4-week loading injections and one 8-week injection, followed by Treat-and-extend (T&E) regimen up to Week 56

3 x 4-week loading injections and disease activity assessment at week 16 followed by q12w/q8w up to Week 56

Outcomes

Primary Outcome Measures

Average change in Best Corrected Visual Acuity (BCVA) from Baseline at a period from Week 48 to Week 60

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Secondary Outcome Measures

Number of participants with last completed treatment interval of 12 weeks and/or 16-weeks with no disease activity at a period from Week 48 to Week 60

As assessed by: BCVA with ETDRS charts Anatomical retinal evaluation of Spectral Domain Optical Coherence Tomography (SD-OCT) images Color fundus photography (CFP) and vascular leakage evaluation by Fluorescein angiography (FA) Polypoidal lesion and Branching vascular network (BVN) evaluation by Indocyanine Green Angiography (ICGA)

Distribution of last completed treatment interval with no disease activity up to Week60

Distribution of the maximal intervals with no disease activity up to Week 60

Distribution of the last interval at a period from Week 48 to Week 60

Time from the last loading injection to the first visit with no disease activity

Occurrence of at least two successive treatment intervals with no disease activity ≥ 12-week or two successive treatment intervals with no disease activity of 16-week up to Week 60

Average change in BCVA from Baseline up to a period from Week 48 to Week 60

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Occurrence of BCVA improvement of ≥ 10 and ≥ 15 letters from Baseline at a period from Week 48 to Week 60

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Occurrence of BCVA ≥ 69 letters at a period from Week 48 to Week 60

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Average change in BCVA from Baseline up to a period from Week 48 to Week 60 categorized into 2 groups, lower half of Baseline BCVA and upper half of Baseline BCVA

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Number of participants with complete polypoidal lesion regression at Week 12 and at a period from Week 48 to Week 60

Polypoidal lesion and Branching vascular network (BVN) evaluation by Indocyanine Green Angiography (ICGA). Polypoidal regression is defined as: Complete polypoidal regression: complete disappearance of any hyper-cyanescent polypoidal lesion previously identified at Baseline Partial polypoidal regression is defined as either partial regression in number (i.e., fewer hyper-cyanescent lesions) compared with Baseline or in size (i.e., smaller hyper-cyanescent lesion) compared with Baseline

Number of participants with inactive polypoidal lesions at Week 12 and at a period from Week 48 to Week 60

Polypoidal lesion and Branching vascular network (BVN) evaluation by Indocyanine Green Angiography (ICGA). Inactive polypoidal lesion is defined as the Absence of polypoidal lesions on ICGA or in case polypoidal lesions were identified or the Absence of new or persistent fluid on OCT or the Absence of leakage on angiography

Change in number and area of polypoidal lesions from Baseline at Week 12 and at a period from Week 48 to Week 60

Polypoidal lesion and Branching vascular network (BVN) evaluation by Indocyanine Green Angiography (ICGA).

Average change from Baseline in central subfield thickness (CSFT) up to Week 60

Change in CSFT from baseline up to week 60 will be analyzed by fitting mixed model repeated measures (MMRM) with observed data including treatment, visit, baseline central subfield thickness (CSFT) categories, age categories and treatment by visit interaction as factors.

Average change from Baseline in maximum thickness of intraretinal fluid (IRF) up to Week 60

Change in maximum thickness of IRF from baseline up to week 60 will be analyzed by fitting mixed model repeated measures (MMRM) with observed data including treatment, visit, baseline central subfield thickness (CSFT) categories, age categories and treatment by visit interaction as factors.

Average change from Baseline in maximum thickness of subretinal fluid (SRF) up to Week 60

Change in maximum thickness of SRF from baseline up to week 60 will be analyzed by fitting mixed model repeated measures (MMRM) with observed data including treatment, visit, baseline central subfield thickness (CSFT) categories, age categories and treatment by visit interaction as factors.

Average change from Baseline in maximum thickness of sub-retinal pigment epithelium (sub-RPE) fluid up to Week 60

Change in maximum thickness of sub-RPE fluid from baseline up to week 60 will be analyzed by fitting mixed model repeated measures (MMRM) with observed data including treatment, visit, baseline central subfield thickness (CSFT) categories, age categories and treatment by visit interaction as factors.

Average change from Baseline in maximum thickness of pigment epithelial detachment (PED) up to Week 60

Change in maximum PED thickness from baseline up to week 60 will be analyzed by fitting mixed model repeated measures (MMRM) with observed data including treatment, visit, baseline central subfield thickness (CSFT) categories, age categories and treatment by visit interaction as factors.

Number of participants with intraretinal fluid (IRF) and/or subretinal fluid (SRF) and/or sub-retinal pigment epithelium (sub-RPE) fluid up to Week 60

As analyzed by fitting mixed model repeated measures (MMRM) with observed data including treatment, visit, baseline central subfield thickness (CSFT) categories, age categories and treatment by visit interaction as factors.

Incidence of ocular adverse events (AEs) up to Week 60

An ocular AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant regarding the eye.

Incidence of non-ocular adverse events (AEs) up to Week 60

An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant.

Full Information

NCT ID

NCT05666804

First Posted

December 19, 2022

Last Updated

April 21, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05666804

Brief Title

Study Assessing the Efficacy and Safety of a Personalized Monotherapy Regimen of Brolucizumab in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy

Acronym

PROUD

Official Title

A 60-week, Phase IIIb, Randomized, Multi-center Study Assessing the Efficacy and Safety of a Personalized Monotherapy Regimen of Brolucizumab in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy (PROUD Study)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 6, 2023 (Actual)

Primary Completion Date

January 31, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This study is a 60-week, two-arm, randomized, open-label, active-controlled, multi-center study in patients with Polypoidal choroidal vasculopathy (PCV) who have not previously received anti-Vascular endothelial growth factor (VEGF) treatment.

Detailed Description

The purpose of this study is to measure the change in Best-corrected visual acuity (BCVA) with brolucizumab 6 mg Personalized regimen compared with Brolucizumab 6 mg Standard q12w/q8w regimen in participants with Polypoidal choroidal vasculopathy (PCV). The study duration will be up to 60 weeks. The treatment duration will be up to 56 weeks. The visit frequency is not fixed and may be reduced or extended depending on whether disease activity is controlled. In the Personalized regimen arm, the first loading injection will be performed for all participants. After 4 weeks, treatment response will be judged. If there is no disease activity, injection interval will be extended to 8 weeks. The participants with presence of disease activity will continue 4-week loading injections up to 3 monthly loading dose and commence the Treat-and-extend (T&E) phase thereafter. In the T&E phase, the treatment interval can be extended by 4 weeks at a time based on Investigator's judgment of visual and/or anatomic outcomes. The maximal treatment interval is 16 weeks. At the Investigator's discretion, a participant with no disease activity or improvement of disease activity (e.g., reduction of fluid) may also be maintained on the same interval. If disease activity recurs, the interval should be shortened by 4 weeks at a time or to a minimal interval of 8 weeks. In the Standard q12w/q8w regimen arm, all participants will receive three loading injections every 4 weeks. After loading injection, participants with no disease activity at Week 16 will receive study treatment q12w at Week 20, Week 32, and Week 44. If there is disease activity at any scheduled treatment visit, the study intervals will be adjusted to 8 weeks thereafter. Treatment intervals can be increased to 12 weeks after a treatment visit with no disease activity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Macular Polypoidal Choroidal Vasculopathy (PCV)

Keywords

Neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, anti-vascular endothelial growth factor, brolucizumab, personalized regimen, treat-and-extend, Retina damage, Retinal disease, Vascular disease, Eye disease, blind spot, fluid leak into or under the retina, blood leak into or under the retina, macular polypoidal choroidal vasculopathy (PCV), PCV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Personalized regimen arm

Arm Type

Experimental

Arm Description

1~3 x 4-week loading injections and one 8-week injection, followed by Treat-and-extend (T&E) regimen up to Week 56

Arm Title

Standard regimen arm

Arm Type

Active Comparator

Arm Description

3 x 4-week loading injections and disease activity assessment at week 16 followed by q12w/q8w up to Week 56

Intervention Type

Drug

Intervention Name(s)

Brolucizumab 6mg

Other Intervention Name(s)

Beovu

Intervention Description

Brolucizumab 6mg (intravitreal) Personalized regimen arm: 1~3 x 4-week loading injections and one 8-week injection, followed by Treat-and-extend (T&E) regimen up to Week 56

Intervention Type

Drug

Intervention Name(s)

Brolucizumab 6mg

Other Intervention Name(s)

Beovu

Intervention Description

Brolucizumab 6mg(intravitreal) Standard q12w/q8w regimen arm: 3 x 4-week loading injections and disease activity assessment at week 16 followed by q12w/q8w up to Week 56

Primary Outcome Measure Information:

Title

Average change in Best Corrected Visual Acuity (BCVA) from Baseline at a period from Week 48 to Week 60

Description

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Time Frame

from Week 48 to Week 60

Secondary Outcome Measure Information:

Title

Number of participants with last completed treatment interval of 12 weeks and/or 16-weeks with no disease activity at a period from Week 48 to Week 60

Description

Time Frame

Week 12, Week 16, and from Week 48 to Week 60

Title

Distribution of last completed treatment interval with no disease activity up to Week60

Description

Time Frame

up to Week 60

Title

Distribution of the maximal intervals with no disease activity up to Week 60

Description

Time Frame

up to Week 60

Title

Distribution of the last interval at a period from Week 48 to Week 60

Description

Time Frame

from Week 48 to Week 60

Title

Time from the last loading injection to the first visit with no disease activity

Description

Time Frame

Up to Week 60

Title

Occurrence of at least two successive treatment intervals with no disease activity ≥ 12-week or two successive treatment intervals with no disease activity of 16-week up to Week 60

Description

Time Frame

up to Week 60

Title

Average change in BCVA from Baseline up to a period from Week 48 to Week 60

Description

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Time Frame

from Week 48 to Week 60

Title

Occurrence of BCVA improvement of ≥ 10 and ≥ 15 letters from Baseline at a period from Week 48 to Week 60

Description

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Time Frame

Baseline, and from Week 48 to Week 60

Title

Occurrence of BCVA ≥ 69 letters at a period from Week 48 to Week 60

Description

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Time Frame

from Week 48 to Week 60

Title

Average change in BCVA from Baseline up to a period from Week 48 to Week 60 categorized into 2 groups, lower half of Baseline BCVA and upper half of Baseline BCVA

Description

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

Time Frame

Baseline, and from Week 48 to Week 60

Title

Number of participants with complete polypoidal lesion regression at Week 12 and at a period from Week 48 to Week 60

Description

Time Frame

at Week 12, and from Week 48 to Week 60

Title

Number of participants with inactive polypoidal lesions at Week 12 and at a period from Week 48 to Week 60

Description

Time Frame

at Week 12, and from Week 48 to Week 60

Title

Change in number and area of polypoidal lesions from Baseline at Week 12 and at a period from Week 48 to Week 60

Description

Polypoidal lesion and Branching vascular network (BVN) evaluation by Indocyanine Green Angiography (ICGA).

Time Frame

Baseline, Week 12, and from Week 48 to Week 60

Title

Average change from Baseline in central subfield thickness (CSFT) up to Week 60

Description

Time Frame

up to Week 60

Title

Average change from Baseline in maximum thickness of intraretinal fluid (IRF) up to Week 60

Description

Time Frame

up to Week 60

Title

Average change from Baseline in maximum thickness of subretinal fluid (SRF) up to Week 60

Description

Time Frame

up to Week 60

Title

Average change from Baseline in maximum thickness of sub-retinal pigment epithelium (sub-RPE) fluid up to Week 60

Description

Time Frame

up to Week 60

Title

Average change from Baseline in maximum thickness of pigment epithelial detachment (PED) up to Week 60

Description

Time Frame

up to Week 60

Title

Number of participants with intraretinal fluid (IRF) and/or subretinal fluid (SRF) and/or sub-retinal pigment epithelium (sub-RPE) fluid up to Week 60

Description

Time Frame

up to Week 60

Title

Incidence of ocular adverse events (AEs) up to Week 60

Description

Time Frame

Up to Week 60

Title

Incidence of non-ocular adverse events (AEs) up to Week 60

Description

An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant.

Time Frame

Up to Week 60

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Novartis Pharmaceuticals

Phone

+41613241111

novartis.email@novartis.com

First Name & Middle Initial & Last Name or Official Title & Degree

Novartis Pharmaceuticals

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Seoul

ZIP/Postal Code

01869

Country

Korea, Republic of

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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.

IPD Sharing Access Criteria

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

IPD Sharing URL

https://www.clinicalstudydatarequest.com/

Learn more about this trial

Study Assessing the Efficacy and Safety of a Personalized Monotherapy Regimen of Brolucizumab in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy

We'll reach out to this number within 24 hrs