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

Phase 3

Completed

• Conditions: Age-Related Macular Degeneration; Wet Macular Degeneration; Macular Degeneration; Retinal Diseases; Eye Diseases; Retinal Degeneration
• Interventions: Biological: brolucuzumab 6 mg IVT

• Registration Number: NCT03954626
• Lead Sponsor: Novartis Pharmaceuticals

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.

Study Timeline

• Study First Submitted: 2019-05-08
• Study First Submitted QC: 2019-05-16
• Study First Posted: 2019-05-17
• Study Start: 2019-06-07
• Primary Completion: 2019-07-09
• Study Completion: 2019-07-31
• Results First Submitted: 2020-06-29
• Status Verified: 2020-08
• Results First Submitted QC: 2020-08-03
• Results First Posted: 2020-08-13
• Last Update Submitted: 2020-12-09
• Last Update Posted: 2021-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RTH258	brolucuzumab 6 mg IVT	Intravitreal injection

Primary Outcome Measures

Name	Time	Method
Frequency of Clinically Relevant Treatment Emergent ECG Changes After Intravitreal Injection of Brolucizumab 6 mg in Patients With nAMD	Baseline, Hour 20, Hour 22, Hour 24	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.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇵🇷 Arecibo, Puerto Rico