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

NCT03954626 | Completed Phase 3 Results FDA Drug

• 1 other identifier: CRTH258A2309
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 3

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).

Conditions

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

Keywords

AMD, nAMD, wet AMD, RTH258, brolucizumab, ECG, open-label

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

RTH258

EXPERIMENTAL

Intravitreal injection

Biological: brolucuzumab 6 mg IVT

Interventions

brolucuzumab 6 mg IVT BIOLOGICAL

Single intravitreal injection (IVT) of brolucizumab 6 mg

Also known as: RTH258

RTH258

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Phoenix, Arizona, 85014, United States

Location

Novartis Investigative Site

Abilene, Texas, 79606, United States

Location

Novartis Investigative Site

Arecibo, 00612, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 35301822 DERIVED

Related Links

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

MeSH Terms

Conditions

Macular Degeneration; Wet Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Interventions

brolucizumab

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

862 778 8300

Study Officials

• Nadia Zakaria, MD

  Novartis Institutes for BioMedical Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: Open label study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm, multicenter

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 17, 2019
• Study Start: June 7, 2019
• Primary Completion: July 9, 2019
• Study Completion: July 31, 2019
• Last Updated: January 5, 2021
• Results First Posted: August 13, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share

Locations

US (2); PR (1)