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出境医 / 临床实验 / Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD

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

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).

Condition or disease Intervention/treatment Phase
Age-Related Macular Degeneration Macular Degeneration Wet Macular Degeneration Retinal Degeneration Retinal Diseases Eye Diseases Biological: brolucuzumab 6 mg IVT Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm, multicenter
Masking: None (Open Label)
Masking Description: Open label study
Primary Purpose: Treatment
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
Actual Study Start Date : June 7, 2019
Actual Primary Completion Date : July 9, 2019
Actual Study Completion Date : July 31, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: RTH258
Intravitreal injection
 Biological: brolucuzumab 6 mg IVT
Single intravitreal injection (IVT) of brolucizumab 6 mg
Other Name: RTH258
Outcome Measures
Primary Outcome Measures :
  1. Frequency of Clinically Relevant Treatment Emergent ECG Changes After Intravitreal Injection of Brolucizumab 6 mg in Patients With nAMD [ Time Frame: 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.


Eligibility Criteria
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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Locations
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United States, Arizona
Novartis Investigative Site
Phoenix, Arizona, United States, 85014
United States, Texas
Novartis Investigative Site
Abilene, Texas, United States, 79606
Puerto Rico
Novartis Investigative Site
Arecibo, Puerto Rico, 00612
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Nadia Zakaria, MD Novartis Institutes for BioMedical Research
Tracking Information
First Submitted Date  ICMJE May 8, 2019
First Posted Date  ICMJE May 17, 2019
Results First Submitted Date  ICMJE June 29, 2020
Results First Posted Date  ICMJE August 13, 2020
Last Update Posted Date January 5, 2021
Actual Study Start Date  ICMJE June 7, 2019
Actual Primary Completion Date July 9, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2020) 		Frequency of Clinically Relevant Treatment Emergent ECG Changes After Intravitreal Injection of Brolucizumab 6 mg in Patients With nAMD [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2019) 		Incidence of clinically relevant treatment emergent ECG changes after intravitreal injection of brolucizumab 6 mg in patients with nAMD [ Time Frame: 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)
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Single arm, multicenter
Masking: None (Open Label)
Masking Description:
Open label study
Primary Purpose: Treatment
Condition  ICMJE
  • Age-Related Macular Degeneration
  • Macular Degeneration
  • Wet Macular Degeneration
  • Retinal Degeneration
  • Retinal Diseases
  • Eye Diseases
Intervention  ICMJE Biological: brolucuzumab 6 mg IVT
Single intravitreal injection (IVT) of brolucizumab 6 mg
Other Name: RTH258
Study Arms  ICMJE Experimental: RTH258
Intravitreal injection
Intervention: Biological: brolucuzumab 6 mg IVT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 24, 2019) 		14
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2019) 		15
Actual Study Completion Date  ICMJE July 31, 2019
Actual Primary Completion Date July 9, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03954626
Other Study ID Numbers  ICMJE CRTH258A2309
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
URL: https://www.clinicalstudydatarequest.com/
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Nadia Zakaria, MD Novartis Institutes for BioMedical Research
PRS Account Novartis
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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