Clinical trial NCT05666804: Study Assessing the Efficacy and Safety of a Personalized Monotherapy Regimen of Brolucizumab in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-12-28
Enrollment: 148
Sex: ALL
Minimum age (years): 50
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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:
3. 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.
4. 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.
5. 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:
6. Previous treatment with any anti-Vascular endothelial growth factor (VEGF) drugs or investigational drugs at any time prior to Baseline.
7. Previous use of intraocular or periocular steroids within the 6-month period prior to Baseline.
8. 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:
9. Stroke or myocardial infarction during the 6-month period prior to Baseline.
10. Systemic anti-VEGF therapy any time prior to Baseline.

Primary outcomes:
measure: Average change in Best Corrected Visual Acuity (BCVA) from Baseline at a period from Week 48 to Week 60
timeFrame: from Week 48 to Week 60
Secondary outcomes:
measure: 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
timeFrame: Week 12, Week 16, and from Week 48 to Week 60
measure: Distribution of last completed treatment interval with no disease activity up to Week60
timeFrame: up to Week 60
measure: Distribution of the maximal intervals with no disease activity up to Week 60
timeFrame: up to Week 60
measure: Distribution of the last interval at a period from Week 48 to Week 60
timeFrame: from Week 48 to Week 60
measure: Time from the last loading injection to the first visit with no disease activity
timeFrame: Up to Week 60
measure: 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
timeFrame: up to Week 60
measure: Average change in BCVA from Baseline up to a period from Week 48 to Week 60
timeFrame: from Week 48 to Week 60
measure: Occurrence of BCVA improvement of ≥ 10 and ≥ 15 letters from Baseline at a period from Week 48 to Week 60
timeFrame: Baseline, and from Week 48 to Week 60
measure: Occurrence of BCVA ≥ 69 letters at a period from Week 48 to Week 60
timeFrame: from Week 48 to Week 60
measure: 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
timeFrame: Baseline, and from Week 48 to Week 60
measure: Number of participants with complete polypoidal lesion regression at Week 12 and at a period from Week 48 to Week 60
timeFrame: at Week 12, and from Week 48 to Week 60
measure: Number of participants with inactive polypoidal lesions at Week 12 and at a period from Week 48 to Week 60
timeFrame: at Week 12, and from Week 48 to Week 60
measure: Change in number and area of polypoidal lesions from Baseline at Week 12 and at a period from Week 48 to Week 60
timeFrame: Baseline, Week 12, and from Week 48 to Week 60
measure: Average change from Baseline in central subfield thickness (CSFT) up to Week 60
timeFrame: up to Week 60
measure: Average change from Baseline in maximum thickness of intraretinal fluid (IRF) up to Week 60
timeFrame: up to Week 60
measure: Average change from Baseline in maximum thickness of subretinal fluid (SRF) up to Week 60
timeFrame: up to Week 60
measure: Average change from Baseline in maximum thickness of sub-retinal pigment epithelium (sub-RPE) fluid up to Week 60
timeFrame: up to Week 60
measure: Average change from Baseline in maximum thickness of pigment epithelial detachment (PED) up to Week 60
timeFrame: up to Week 60
measure: 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
timeFrame: up to Week 60
measure: Incidence of ocular adverse events (AEs) up to Week 60
timeFrame: Up to Week 60
measure: Incidence of non-ocular adverse events (AEs) up to Week 60
timeFrame: Up to Week 60
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Dalseo Gu
city: Bundang Gu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Daejeon
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Daegu
country: Korea, Republic of
facility: Novartis Investigative Site
city: Gwangju
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: