Age-Related Macular Degeneration, Eye Diseases, Macular Degeneration, Retinal Degeneration, Retinal Diseases, Wet Macular Degeneration
Conditions
Keywords
AMD, nAMD, wet AMD, RTH258, brolucizumab, ECG, open-label
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.
Interventions
BIOLOGICALbrolucuzumab 6 mg IVT
Single intravitreal injection (IVT) of brolucizumab 6 mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label study
Intervention model description
Single arm, multicenter
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Clinically Relevant Treatment Emergent ECG Changes After Intravitreal Injection of Brolucizumab 6 mg in Patients With nAMD | 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. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
The study enrolled patients from 3 centers from the United States.14 patients were enrolled and analyzed in the study.
Participants by arm
| Arm | Count |
|---|---|
| RTH258 Intravitreal injection | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | RTH258 |
|---|---|
| Age, Continuous | 75.7 years STANDARD_DEVIATION 6.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 1 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
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.
Time frame: Baseline, Hour 20, Hour 22, Hour 24
Population: The safety analysis, which included all patients who received one intravitreal injection of brolucizumab 6 mg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RTH258 | Frequency of Clinically Relevant Treatment Emergent ECG Changes After Intravitreal Injection of Brolucizumab 6 mg in Patients With nAMD | 0 Number of events |