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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05666804
• Collaborator: (none)
• Enrollment: 160
• Locations: 14
• Arms: 2
• Anticipated Duration (Months): 23
• Patients Per Site: 11.4
• Patients Per Site Per Month: 0.5

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Macular Polypoidal Choroidal Vasculopathy (PCV)	Drug: Brolucizumab 6mg; Drug: Brolucizumab 6mg	Phase 3

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Anticipated Study Start Date: Jan 31, 2023
• Anticipated Primary Completion Date: Jan 31, 2024
• Anticipated Study Completion Date: Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Brolucizumab 6mg; 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; Other Names: Beovu
Active Comparator: Standard regimen arm 3 x 4-week loading injections and disease activity assessment at week 16 followed by q12w/q8w up to Week 56	Drug: Brolucizumab 6mg; 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; Other Names: Beovu

Outcome Measures

Primary Outcome Measures

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

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

Secondary Outcome Measures

1. 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 [Week 12, Week 16, and 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)

2. Distribution of last completed treatment interval with no disease activity up to Week60 [up 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)

3. Distribution of the maximal intervals with no disease activity up to Week 60 [up 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)

4. Distribution of the last interval at a period from Week 48 to Week 60 [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)

5. Time from the last loading injection to the first visit with no disease activity [Up 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)

6. 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 [up 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)

7. Average change in BCVA from Baseline up to a period from Week 48 to Week 60 [from Week 48 to Week 60]

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

8. Occurrence of BCVA improvement of ≥ 10 and ≥ 15 letters from Baseline at a period from Week 48 to Week 60 [Baseline, and from Week 48 to Week 60]

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

9. Occurrence of BCVA ≥ 69 letters at a period from Week 48 to Week 60 [from Week 48 to Week 60]

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

10. 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 [Baseline, and from Week 48 to Week 60]

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

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

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

13. Change in number and area of polypoidal lesions from Baseline at Week 12 and at a period from Week 48 to Week 60 [Baseline, Week 12, and from Week 48 to Week 60]

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

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

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

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

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

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

19. 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 [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.

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

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.

2. Participants ≥ 50 years of age at Screening.

Study eye:

1. 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.

2. 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.

3. 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:

1. 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.

2. 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.

3. 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.

4. Any Polypoidal choroidal vasculopathy (PCV) masquerades like macular aneurysms, macular telangiectasia, etc. in study eye.

5. 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:

1. Previous treatment with any anti-Vascular endothelial growth factor (VEGF) drugs or investigational drugs at any time prior to Baseline.

2. Previous use of intraocular or periocular steroids within the 6-month period prior to Baseline.

3. 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:

1. Stroke or myocardial infarction during the 6-month period prior to Baseline.

2. Systemic anti-VEGF therapy any time prior to Baseline.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Inje university Haeundae Paik Hospital	Busan		Korea, Republic of
2	Pusan National University Hospital	Busan		Korea, Republic of
3	Keimyung University Dongsan Medical Center	Daegu		Korea, Republic of
4	Yeungnam University Hospital	Daegu		Korea, Republic of
5	Chungnam National University Hospital	Daejeon		Korea, Republic of
6	Chonnam National University Hospital	Gwangju		Korea, Republic of
7	Seoul National University Bundang Hospital	Gyeonggi-do		Korea, Republic of
8	Asan Medical Center	Seoul		Korea, Republic of
9	Gangnam Severance Hospital	Seoul		Korea, Republic of
10	Kim's eye hospital	Seoul		Korea, Republic of
11	KyungHee University Medical Center	Seoul		Korea, Republic of
12	Nune eye hospital	Seoul		Korea, Republic of
13	Seoul National University Hospital	Seoul		Korea, Republic of
14	Severance Hospital	Seoul		Korea, Republic of

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05666804
• Other Study ID Numbers: CRTH258AKR03
• First Posted: Dec 28, 2022
• Last Update Posted: Dec 28, 2022
• Last Verified: Dec 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: 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
• Additional relevant MeSH terms: Vascular Diseases

Study Results

No Results Posted as of Dec 28, 2022