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

NCT ID: NCT03954626

Last Updated: 2021-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-07
• Study Completion Date: 2019-07-31

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.

Conditions

Age-Related Macular Degeneration; Macular Degeneration; Wet Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RTH258

Intravitreal injection

Group Type: EXPERIMENTAL

brolucuzumab 6 mg IVT

Intervention Type: BIOLOGICAL

Single intravitreal injection (IVT) of brolucizumab 6 mg

Interventions

brolucuzumab 6 mg IVT

Single intravitreal injection (IVT) of brolucizumab 6 mg

Intervention Type: BIOLOGICAL

Other Intervention Names

RTH258

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nadia Zakaria, MD

Role: STUDY_DIRECTOR

Novartis Institutes for BioMedical Research

Locations

Novartis Investigative Site

Phoenix, Arizona, United States

Novartis Investigative Site

Abilene, Texas, United States

Novartis Investigative Site

Arecibo, , Puerto Rico

Countries

United States; Puerto Rico

References

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.

Reference Type: DERIVED

PMID: 35301822 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=383

A Plain Language Trial Summary is available on novartisclinicatrials.com

Other Identifiers

CRTH258A2309

Identifier Type: -

Identifier Source: org_study_id