Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD
Primary Purpose
Age-Related Macular Degeneration, Macular Degeneration, Wet Macular Degeneration
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
brolucuzumab 6 mg IVT
Sponsored by
About this trial
This is an interventional treatment trial for Age-Related Macular Degeneration focused on measuring AMD, nAMD, wet AMD, RTH258, brolucizumab, ECG, open-label
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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
RTH258
Arm Description
Intravitreal injection
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03954626
Brief Title
Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
June 7, 2019 (Actual)
Primary Completion Date
July 9, 2019 (Actual)
Study Completion Date
July 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Single arm, multicenter
Masking
None (Open Label)
Masking Description
Open label study
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RTH258
Arm Type
Experimental
Arm Description
Intravitreal injection
Intervention Type
Biological
Intervention Name(s)
brolucuzumab 6 mg IVT
Other Intervention Name(s)
RTH258
Intervention Description
Single intravitreal injection (IVT) of brolucizumab 6 mg
Primary Outcome Measure Information:
Title
Frequency of Clinically Relevant Treatment Emergent ECG Changes After Intravitreal Injection of Brolucizumab 6 mg in Patients With nAMD
Description
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.
Time Frame
Baseline, Hour 20, Hour 22, Hour 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nadia Zakaria, MD
Organizational Affiliation
Novartis Institutes for BioMedical Research
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85014
Country
United States
Facility Name
Novartis Investigative Site
City
Abilene
State/Province
Texas
ZIP/Postal Code
79606
Country
United States
Facility Name
Novartis Investigative Site
City
Arecibo
ZIP/Postal Code
00612
Country
Puerto Rico
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/
Citations:
PubMed Identifier
35301822
Citation
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.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=383
Description
A Plain Language Trial Summary is available on novartisclinicatrials.com
Learn more about this trial
Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD
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