Age-Related Macular DegenerationPhase 3NCT03954626
Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD
A Phase 3 study testing brolucuzumab 6 mg IVT in people with Age-Related Macular Degeneration and Macular Degeneration, run by Novartis Pharmaceuticals at 3 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Age-Related Macular Degeneration, Macular Degeneration, Wet Macular Degeneration
- What is being tested?
- brolucuzumab 6 mg IVT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 7 Jun 2019to 31 Jul 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Novartis Investigative Site
Abilene, Texas, 79606
Novartis Investigative Site
Phoenix, Arizona, 85014
About this study
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
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).
Read the 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
- Being tested
- brolucuzumab 6 mg IVT
- Keywords
- AMD, nAMD, wet AMD, RTH258, brolucizumab, ECG, open-label
- Medical subject headings
- Macular Degeneration, Wet Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
brolucuzumab 6 mg IVTBiological
Also called RTH258
Single intravitreal injection (IVT) of brolucizumab 6 mg
| Study group | Role | What they receive |
|---|---|---|
| RTH258 | Experimental | Intravitreal injection Receives: Biological: brolucuzumab 6 mg IVT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Hour 20, Hour 22, Hour 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2019
- Study start7 Jun 2019
- Primary completion9 Jul 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Age-Related Macular DegenerationStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, multicenter
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nadia Zakaria, MD, Study director, Novartis Institutes for BioMedical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03954626
- Sponsor's protocol ID
- CRTH258A2309
- Status last verified
- Aug 2020
- First submitted
- 8 May 2019
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 35301822
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03954626
- Acronym / sponsor ID
- CRTH258A2309
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Jun 2019 (actual)
- Primary completion
- 9 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 17 May 2019 (actual)
- Results
- Posted 13 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, multicenter
| Arm | Type | Receives |
|---|---|---|
| RTH258 | Experimental | Biological: brolucuzumab 6 mg IVTIntravitreal injection |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (19 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| brolucuzumab 6 mg IVTAlso: RTH258Single intravitreal injection (IVT) of brolucizumab 6 mg | Biological | RTH258 |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35301822Zakaria 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.
- A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nadia Zakaria, MD study director
Novartis Institutes for BioMedical Research
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing brolucuzumab 6 mg IVT in people with Age-Related Macular Degeneration and Macular Degeneration, run by Novartis Pharmaceuticals at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03954626, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.