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

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

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).

Study Overview

• Status: Completed
• Conditions: Eye Diseases; Age-Related Macular Degeneration; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Wet Macular Degeneration
• Intervention / Treatment: Biological: brolucuzumab 6 mg IVT

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Novartis Investigative Site
  • Texas
    • Abilene, Texas, United States, 79606
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RTH258; Intravitreal injection	Biological: brolucuzumab 6 mg IVT; Single intravitreal injection (IVT) of brolucizumab 6 mg; 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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Nadia Zakaria, MD, Novartis Institutes for BioMedical Research

Publications and helpful links

General Publications

• Zakaria N, Guerard N, Emanuelli A, Dugel P, Watts J, Liew M, Gekkieva M, Hinder M. Evaluation of cardiac parameters and other safety outcomes of brolucizumab treatment in patients with neovascular age-related macular degeneration. Pharmacol Res Perspect. 2022 Apr;10(2):e00897. doi: 10.1002/prp2.897.

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2019
• Primary Completion (Actual): July 9, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: May 8, 2019
• First Submitted That Met QC Criteria: May 16, 2019
• First Posted (Actual): May 17, 2019

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: AMD, nAMD, wet AMD, RTH258, brolucizumab, ECG, open-label
• Additional Relevant MeSH Terms: Eye Diseases, Hereditary; Macular Degeneration; Retinal Diseases; Eye Diseases; Wet Macular Degeneration; Retinal Degeneration
• Other Study ID Numbers: CRTH258A2309

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No