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Neovascular Age-related Macular DegenerationPhase 3NCT03386474

Study of Safety and Efficacy of Brolucizumab 6 mg Drug Product Intended for Commercialization in Patients With nAMD

A Phase 3 study testing Brolucizumab 6 mg and Aflibercept 2 mg in people with Neovascular Age-related Macular Degeneration, run by Novartis Pharmaceuticals at 65 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this extension study was to assess the safety and efficacy of the new formulation of brolucizumab 6 mg ophthalmic solution when given to the same patients who received brolucizumab in the core trial CRTH258A2301 (also known as CRTH258-C002). Read more about this study

Who is it for?
Ages 50 years and older
What is being tested?
Brolucizumab 6 mg and Aflibercept 2 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
151 participants
Where
65 sitesin 2 countries
Study dates
15 Jan 2018to 6 Sep 2018
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

  • Sign written informed consent
  • Completed the core study, CRTH258A2301, also known as CRTH258-C002 as defined by assessments at Visit 26/Week 96 within ≤12 weeks of the baseline.

Who cannot join

  • Patient discontinued the treatment or the core study prematurely at any time
  • Patient received standard of care treatment for nAMD after completion of the core study
  • Pregnant or nursing women and women of child-bearing potential
  • Stroke or MI (myocardial infarction) within 3 months of the baseline extension visit

Trial locations and contacts

65 sites in 2 countries.

65 sites in 2 countries

United States63 sites

  • Novartis Investigative Site

    Abilene, Texas, 79606

  • Novartis Investigative Site

    Albuquerque, New Mexico, 87102

  • Novartis Investigative Site

    Altamonte Springs, Florida, 32701

  • Novartis Investigative Site

    Arcadia, California, 91006

  • Novartis Investigative Site

    Austin, Texas, 78731

  • Novartis Investigative Site

    Baltimore, Maryland, 21237-4350

  • Novartis Investigative Site

    Bloomington, Illinois, 61704

  • Novartis Investigative Site

    Boise, Idaho, 83713

  • Novartis Investigative Site

    Bridgeport, Connecticut, 06606

  • Novartis Investigative Site

    Camp Hill, Pennsylvania, 17011

  • Novartis Investigative Site

    Charlotte, North Carolina, 28210

  • Novartis Investigative Site

    Cleveland, Ohio, 44122

  • Novartis Investigative Site

    Cleveland, Ohio, 44195

  • Novartis Investigative Site

    Colorado Springs, Colorado, 80909

  • Novartis Investigative Site

    Deerfield Beach, Florida, 33064

  • Novartis Investigative Site

    Dublin, Ohio, 43016

  • Novartis Investigative Site

    Fairfield, Ohio, 45014

  • Novartis Investigative Site

    Fort Myers, Florida, 33912-7125

  • Novartis Investigative Site

    Fort Worth, Texas, 76104

  • Novartis Investigative Site

    Golden, Colorado, 80401

  • Novartis Investigative Site

    Houston, Texas, 77025

  • Novartis Investigative Site

    Houston, Texas, 77030

  • Novartis Investigative Site

    Huntington Beach, California, 92647

  • Novartis Investigative Site

    Indianapolis, Indiana, 46280

  • Novartis Investigative Site

    La Jolla, California, 92093

  • Novartis Investigative Site

    Las Vegas, Nevada, 89144

  • Novartis Investigative Site

    Leawood, Kansas, 66211

  • Novartis Investigative Site

    Loma Linda, California, 92354

  • Novartis Investigative Site

    Milwaukee, Wisconsin, 53226

  • Novartis Investigative Site

    Morgantown, West Virginia, 26506

  • Novartis Investigative Site

    Mountain View, California, 94040

  • Novartis Investigative Site

    Nashville, Tennessee, 37203

  • Novartis Investigative Site

    New London, Connecticut, 06320

  • Novartis Investigative Site

    Oakland, California, 94609

  • Novartis Investigative Site

    Ocala, Florida, 34474

  • Novartis Investigative Site

    Palm Beach Gardens, Florida, 33410

  • Novartis Investigative Site

    Pensacola, Florida, 32503

  • Novartis Investigative Site

    Peoria, Arizona, 85381

  • Novartis Investigative Site

    Phoenix, Arizona, 85014

  • Novartis Investigative Site

    Plano, Texas, 75093

  • Novartis Investigative Site

    Portland, Maine, 04102

  • Novartis Investigative Site

    Redlands, California, 92374

  • Novartis Investigative Site

    Reno, Nevada, 89502

  • Novartis Investigative Site

    Richmond, Virginia, 23235

  • Novartis Investigative Site

    Rochester, New York, 14620

  • Novartis Investigative Site

    Rochester, New York, 14642

  • Novartis Investigative Site

    Sacramento, California, 95841

  • Novartis Investigative Site

    San Antonio, Texas, 78215

  • Novartis Investigative Site

    San Antonio, Texas, 78240

  • Novartis Investigative Site

    Sarasota, Florida, 34239

  • Novartis Investigative Site

    Shawnee Mission, Kansas, 66204

  • Novartis Investigative Site

    Shirley, New York, 11967

  • Novartis Investigative Site

    Silverdale, Washington, 98383

  • Novartis Investigative Site

    Southern Pines, North Carolina, 28387

  • Novartis Investigative Site

    Spokane, Washington, 99204

  • Novartis Investigative Site

    Syracuse, New York, 13224

  • Novartis Investigative Site

    Tallahassee, Florida, 32308

  • Novartis Investigative Site

    Toms River, New Jersey, 08755

  • Novartis Investigative Site

    University Place, Washington, 98467

  • Novartis Investigative Site

    Vero Beach, Florida, 32960

  • Novartis Investigative Site

    Waldorf, Maryland, 20602

  • Novartis Investigative Site

    Warrenton, Virginia, 20186

  • Novartis Investigative Site

    Winter Haven, Florida, 33880

Other trials in United States

Puerto Rico2 sites

  • Novartis Investigative Site

    Arecibo, 00612

  • Novartis Investigative Site

    San Juan, 00907

Other trials in Puerto Rico

About this study

Official title: A 24-week, Double-masked, Multicenter, Two-arm Extension Study to Collect Safety and Efficacy Data on Brolucizumab 6 mg Drug Product Intended for Commercialization in Patients With Neovascular Age-related Macular Degeneration Who Have Completed the CRTH258A2301 Study

The purpose of this extension study was to assess the safety and efficacy of the new formulation of brolucizumab 6 mg ophthalmic solution when given to the same patients who received brolucizumab in the core trial CRTH258A2301 (also known as CRTH258-C002). The medical condition treated in the core and extension trials was neo-vascular age-related macular degeneration (nAMD).

Read the detailed description

Subjects in the United States who had completed the 96 week core trial, CRTH258A2301 (also referred as CRTH258-C002), were eligible to participate in the extension trial provided the core trial Visit 26 at week 96, was less than or equal to 12 weeks from the Baseline Visit in the extension trial, CRTH258A2301E1.

Subjects who were treated with aflibercept during the core trial and met the eligibility requirements of this extension trial continued to receive aflibercept in this extension trial in order to maintain the masking during the extension trial. No hypothesis testing or descriptive analyses were planned.

Subjects who were treated in the core trial with brolucizumab 3mg or brolucizumab 6 mg, and met the eligibility requirements of this extension trial, received the new formulation of brolucizumab 6 mg solution in the extension trial.

Enrolled subjects were to receive three intravitreal (IVT) ophthalmic injections. The study eye was the same eye that received the treatment in the core study. The extension trial consisted of 7 study visits at 4 week intervals over a period of 24 weeks.

Assessment of the efficacy and safety of brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding core-study efficacy and safety data serving as the reference. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned.

Being tested
Brolucizumab 6 mg, Aflibercept 2 mg
Keywords
double-masked, extension study, neovascular age-related macular degeneration, intravitreal injection, brolucizumab, aflibercept

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brolucizumab 6 mgDrug

    Also called RTH258

    Administered as opthalmic solution for an intravitreal injection to the study eye

  • Aflibercept 2 mgDrug

    Also called EYELEA

    Administered as an opthalmic solution for intravitreal injection to the study eye

Study groups in NCT03386474
Study groupRoleWhat they receive
BrolucizumabExperimentalBrolucizumab 6 mg solution for IVT injection, single injection at Day 1 (baseline), Week 8, and Week 16 or Week 20
Receives: Drug: Brolucizumab 6 mg
AfliberceptOtherAflibercept 2 mg solution for IVT injection, single injection at Day 1 (baseline), Week 8 and Week 16 to maintain the masking of the extension trial only.
Receives: Drug: Aflibercept 2 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events

    Number of participants with ocular and non-ocular treatment emergent events with the new formulation brolucizumab 6 mg in this extension trial up to week 24 vs. the corresponding last 6 months of brolucizumab treatment in the Core trial >= 2%. Safety assessment of the new formulation brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding Core safety data. Missing brolucizumab data were imputed using last observation carried forward (LOCF).

    Measured: Up to Week 24

Secondary outcomes (5)

  1. Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit

    Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data presented descriptively for only brolucizumab in line with study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).

    Measured: Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24

  2. Change in BCVA From Extension Baseline at Each Post-baseline Visit

    Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).

    Measured: Extension baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24

  3. Patients With Positive q12w Treatment Status at Week 20

    The estimate for the proportion of patients with a positive q12w treatment status at Week 24 was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need'. The outcome of the Kaplan-Meier analysis was estimated probability for maintaining on q12w up to the Disease Activity Assessment (DAA) at exWeek 20. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).

    Measured: Week 20

  4. Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit

    Measurement of the central subfield thickness of the retina was assessed using Optical Coherence Tomography (OCT) at each visit for the study eye. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).

    Measured: Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24

  5. Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status for Brolucuzumab 6 mg in Extension

    Positive integrated anti-drug antibodies (ADA) status is defined as induced ADA status with ADA negative at pre-dose and a post-dose titer value of greater than or equal to 30 at any time point or boosted ADA status with ADA positive at pre-dose and a post-dose titer value increase by more than 3-fold (1 dilution) at any time point. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).

    Measured: Extension Baseline, Week 8, Week 16, Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Dec 2017
  2. Study start15 Jan 2018
  3. Primary completion6 Sep 2018
  4. Study completion6 Sep 2018

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
151 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03386474
Sponsor's protocol ID
CRTH258A2301E1
Status last verified
Mar 2020
First submitted
11 Dec 2017
Last updated
5 Jan 2021
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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Brolucizumab 6 mg and Aflibercept 2 mg in people with Neovascular Age-related Macular Degeneration, run by Novartis Pharmaceuticals at 65 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 4 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 65 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 30 Apr 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?

Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events (time frame: Up to Week 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 NCT03386474.

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.

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