Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to collect ECG data after a single IVT injection of brolucizumab 6 mg in patients with neovascular age-related macular degeneration (nAMD).

Detailed Description
-----------------
This is a single-arm, open-label, multicenter study that collected ECG data after a single IVT injection of brolucizumab 6 mg in patients with nAMD. Triplicate 12-lead ECG recording was performed at screening to determine eligibility. A second triplicate 12-lead ECG recording was collected approximately 2h prior to the brolucizumab IVT injection on Day 1. Holter ECG recording started approximately 1 h prior to the brolucizumab IVT injection and ended approximately 48h after the IVT injection. A third triplicate 12-lead ECG recording was performed after the conclusion of Holter monitoring on Day 3.

Official Title
-----------------
A Single-Arm, Open-Label, Multicenter, Phase IIIb Study to Collect Safety and Electrocardiogram Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Neovascular Age-Related Macular Degeneration

Conditions
-----------------
Age-Related Macular Degeneration, Macular Degeneration, Wet Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases

Intervention / Treatment
-----------------
* Biological: brolucuzumab 6 mg IVT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent MUST be obtained prior to participation in the study Study eye is diagnosed with nAMD and deemed to be eligible for intravitreal injection at the discretion of the Investigator Exclusion Criteria: Concomitant conditions or ocular disorders in the study eye at screening which may cause safety concerns on the judgement of the investigator Any active intraocular or periocular or systemic infection or active intraocular inflammation at Baseline Treatment with any ocular intravitreal injection in the study eye within the past 7 half lives prior to Baseline Intraocular surgery, prior long-acting therapeutic agent, or ocular drug release device implantation (approved or investigational) in the study eye any time during the past 3 months prior to Baseline Diagnosis of ECG abnormalities including: Clinically significant cardiac arrhythmias, e.g., atrial fibrillation, sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker Familial long QT syndrome or known family history of Torsades de Pointes Resting heart rate < 50 or > 90 bpm at screening Resting QTcF ≥ 450 ms (male) or ≥ 460 ms (female) at screening Use of concomitant medications that are classified as known risk, conditional risk or possible risk to prolong QT/QTc interval within 7 half-lives prior to Baseline History of stroke (including transient ischemic attack, reversible ischemic neurological deficit, prolonged reversible ischemic neurological deficit) or myocardial infarction (ST or non-ST elevation myocardial infarction) at any time prior to baseline Chronic kidney disease as determined as a CrCL at screening of < 60 ml/min/1.73 m2 as determined by the MDRD formula Uncontrolled high blood pressure defined as a systolic value ≥ 140 mmHg or diastolic value ≥ 90 mmHg at screening or baseline Systemic anti-VEGF therapy during the 6-month period prior to baseline Electrolyte disturbances determined as out of normal range sodium, potassium or calcium serum concentrations at screening Concomitant intake of long-acting muscarinic antagonist (LAMA)/ long-acting beta adrenergic (LABA) combination therapy History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar classes as assessed by the investigator Use of systemic or ocular (including intravitreal) investigational drugs within 7 half-lives of baseline, (or within 30 days/until the expected pharmacodynamic effect has returned to baseline), whichever is longer or longer if required by local regulations (observational clinical studies solely involving over-the-counter vitamins, supplements, or diets are not exclusionary) Pregnant or nursing (lactating) women

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm, multicenter
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RTH258<br>Intravitreal injection | Biological: brolucuzumab 6 mg IVT<br>* Single intravitreal injection (IVT) of brolucizumab 6 mg<br>* Other names: RTH258;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Clinically Relevant Treatment Emergent ECG Changes After Intravitreal Injection of Brolucizumab 6 mg in Patients With nAMD | Incidence between 20 and 24 h post-injection of clinically relevant treatment emergent changes in heart rate (HR), pulse rate (PR), QRS, and QTc (heart rate corrected QT using Fridericia's formula, QTcF) interval (ms). This is a composite endpoint capturing all 4 parameters and 3 time-points in one Outcome Measure. | Baseline, Hour 20, Hour 22, Hour 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AMD, nAMD, wet AMD, RTH258, brolucizumab, ECG, open-label