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Neovascular Age Related Macular DegenerationPhase 3OCTOPUSNCT04239027

A Study to Assess the Effects of Brolucizumab in Adult Patients With Neovascular Age Related Macular Degeneration

A Phase 3 study testing RTH258/Brolucizumab in people with Neovascular Age Related Macular Degeneration, run by Novartis Pharmaceuticals at 40 sites in France.

Completed

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

Official record
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Trial summary

Neovascular age-related macular degeneration (nAMD) is characterized by the presence of choroidal neovascularization (CNV). Choroidal neovascularization consists of abnormal blood vessels originating from the choroid and can lead to hemorrhage, fluid exudation, and fibrosis, resulting in photoreceptor damage and… Read more about this study

Who is it for?
Ages 50 years and older
What is being tested?
RTH258/Brolucizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
210 participants
Where
40 sitesFrance
Study dates
26 Jan 2021to 2 Feb 2023
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

  • Patients must provide written informed consent before any study related procedures are performed.
  • Patients must be 50 years of age or older at Screening/Baseline.
  • Study eye:
  • Active CNV lesions secondary to AMD that affect the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography and sequellae of CNV, e.g. pigment epithelial detachment (PED), subretinal hemorrhage or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema.
  • Intra- and/or subretinal fluid affecting the central subfield of the study eye at Screening/Baseline.
  • BCVA between 83 and 23 letters, inclusive, in the study eye at Screening/Baseline using early treatment diabetic retinopathy study (ETDRS) at an initial testing distance of 4 meters.

Who cannot join

  • Ocular conditions:
  • Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in either eye at Screening/Baseline.
  • Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 35 ETDRS letters at Screening (except when due to conditions whose surgery may improve visual acuity, e.g. cataract).
  • Medical history of intraocular inflammation and/or retinal vascular occlusion within 12 months prior to Screening/Baseline.
  • Study eye:
  • Poor quality of OCT-A and SD-OCT images at Screening/Baseline.
Show all 35Show fewer
  • Atrophy or fibrosis involving the center of the fovea in the study eye, as assessed by color fundus photography and fundus autofluorescence (FAF) at Screening/Baseline.
  • The total area of fibrosis or subretinal blood affecting the foveal center point comprising ≥ 50% of the lesion area in the study eye at Screening/Baseline.
  • Concomitant conditions or ocular disorders in the study eye, including retinal diseases other than nAMD, that, in the judgment of the investigator, could require medical or surgical intervention during the course of the study to prevent or treat visual loss that might result from that condition, or that limits the potential to gain visual acuity upon treatment with the investigational product.
  • Structural damage within 0.5 disc diameter of the center of the macula in the study eye, e.g. vitreomacular traction, epiretinal membrane, retinal pigment epithelium (RPE) rip/tear scar, laser burn, at the time of Screening that in the investigator's opinion could preclude visual function improvement with treatment.
  • Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Screening/Baseline.
  • Uncontrolled glaucoma in the study eye defined as IOP > 25 mmHg on medication or according to the investigator's judgment at Screening/Baseline.
  • Aphakia and/or absence of the posterior capsule in the study eye at Screening/Baseline.
  • Ocular treatments (study eye):
  • Patient has received any approved or investigational treatment for nAMD (other than vitamin supplements) in the study eye at any time.
  • Intraocular or periocular use of corticosteroids in the study eye during the 6-month period prior to Screening/Baseline.
  • Previous penetrating keratoplasty or vitrectomy at any time prior to Screening/Baseline.
  • History or evidence of the following in the study eye within the 90-day period prior to Screening/Baseline:
  • Intraocular or refractive surgery.
  • Previous panretinal photocoagulation.
  • Previous submacular surgery, other surgical intervention or laser treatment for nAMD including photodynamic therapy (PDT).
  • Systemic conditions or treatments:
  • End stage renal disease requiring dialysis or renal transplant.
  • Systemic medications known to be toxic to the lens, retina or optic nerve (e.g. deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol) used during the 6-month period prior to Screening/Baseline except temporary use for COVID-19 treatment.
  • Participation in an investigational drug, biologic, or device study within 30 days or the duration of 5 half-lives of the investigational product (whichever is longer) prior to Screening/Baseline. Note: observational clinical studies solely involving over-the-counter vitamins, supplements, or diets are not exclusionary.
  • Systemic anti-VEGF therapy at any time.
  • Stroke or myocardial infarction in the 6-month period prior to Screening/Baseline.
  • Uncontrolled blood pressure defined as a systolic value ≥ 160 mmHg or diastolic value ≥ 100 mmHg at Screening/Baseline. (In case there is an elevated blood pressure measurement, it should be repeated after 20 minutes. If the repeat measurement is elevated, then the patient is not eligible to be enrolled into the study).
  • History of a medical condition (disease, metabolic dysfunction with exception of type 1 or 2 diabetes mellitus, physical examination finding, or clinical laboratory finding) that, in the judgment of the investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product.
  • History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
  • History of hypersensitivity to any component of the test article, control article, or clinically relevant sensitivity to fluorescein dye, as assessed by the investigator.
  • Other:
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) pregnancy test.
  • Women of childbearing potential, defined as all women less than 1 year postmenopausal or less than 6 weeks since sterilization at Screening/Baseline Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential.
  • Patients mentioned in Articles L.1121-5 to L.1121-8 and L.1122-1-2 of the Code de Santé Publique (e.g. minors, protected adults, etc.)

Trial locations and contacts

40 sites in 1 country.

40 sites in 1 country

France40 sites

  • Novartis Investigative Site

    Aix-en-Provence, 13090

  • Novartis Investigative Site

    Angers, 49044

  • Novartis Investigative Site

    Avignon, 84000

  • Novartis Investigative Site

    Bobigny, Seine Saint Denis, 93009

  • Novartis Investigative Site

    Bordeaux, 33000

  • Novartis Investigative Site

    Boulogne-sur-Mer, 62321

  • Novartis Investigative Site

    Caen, 14000

  • Novartis Investigative Site

    Caen, 14033

  • Novartis Investigative Site

    Créteil, 94000

  • Novartis Investigative Site

    Dijon, 21034

  • Novartis Investigative Site

    Floirac, 33270

  • Novartis Investigative Site

    Grenoble, 38000

  • Novartis Investigative Site

    La Rochelle, 17019

  • Novartis Investigative Site

    Lagord, 17140

  • Novartis Investigative Site

    Le Chesnay, 78157

  • Novartis Investigative Site

    Lille, 59000

  • Novartis Investigative Site

    Lyon, Rhone, 69317

  • Novartis Investigative Site

    Lyon, 69002

  • Novartis Investigative Site

    Marseille, F 13008

  • Novartis Investigative Site

    Montargis, 45200

  • Novartis Investigative Site

    Montauban, 82000

  • Novartis Investigative Site

    Montpellier, 34000

  • Novartis Investigative Site

    Mulhouse, 68070

  • Novartis Investigative Site

    Nantes, 44093

  • Novartis Investigative Site

    Nantes, 44300

  • Novartis Investigative Site

    Nice, Cedex1, 06001

  • Novartis Investigative Site

    Paris, 75007

  • Novartis Investigative Site

    Paris, 75010

  • Novartis Investigative Site

    Perpignan, 66000

  • Novartis Investigative Site

    Plérin, 22190

  • Novartis Investigative Site

    Poitiers, 86021

  • Novartis Investigative Site

    Rennes, FRA, 35033

  • Novartis Investigative Site

    Rouen, 76100

  • Novartis Investigative Site

    Royan, 17200

  • Novartis Investigative Site

    Rueil-Malmaison, 92500

  • Novartis Investigative Site

    Saint-Cyr-sur-Loire, Indre Et Loire, 37540

  • Novartis Investigative Site

    Saint-Herblain, 44819

  • Novartis Investigative Site

    Saint-Martin-des-Champs, 50300

  • Novartis Investigative Site

    Strasbourg, 67000

  • Novartis Investigative Site

    Toulouse, 31059

Other trials in France

About this study

Official title: A One-year, Single-arm, Open-label, Multicenter Study Assessing the Anatomic Outcomes of Brolucizumab Assessed by OCT-A in Adult Patients With Neovascular Age Related Macular Degeneration

Neovascular age-related macular degeneration (nAMD) is characterized by the presence of choroidal neovascularization (CNV). Choroidal neovascularization consists of abnormal blood vessels originating from the choroid and can lead to hemorrhage, fluid exudation, and fibrosis, resulting in photoreceptor damage and vision loss.

The safety and efficacy of brolucizumab has been demonstrated in 2 randomized, multicenter, double-masked, active controlled Phase 3 studies in nAMD patients (RTH258-C001 and RTH258-C002). Anatomical changes were evaluated in these studies using spectral domain optical coherence tomography (SD-OCT), which relied on indirect parameters for the diagnosis of active CNV. The OCT-angiography (OCT A) that directly visualize retinal circulation and image CNV and vascular diseases of the retina was not included in previous brolucizumab studies.

Read more

This single-arm, open-label, multicenter study was performed to evaluate the efficacy and safety of brolucizumab 6 mg in patients with nAMD.

OCT-A was used in this study to assess the morphological response of patients to brolucizumab in terms of percentage change in CNV lesion area in the short term (i.e. at Week 12) and in the long term (i.e. at Week 48), as well as changes in other OCT-A features up to Week 48.

Read the detailed description

This was a prospective, single-arm, open-label, multicenter study to evaluate the efficacy and safety of brolucizumab 6 mg in patients with neovascular age-related macular degeneration (nAMD). Patients were required to attend 6 mandatory study visits: Screening/Baseline Visit (Day 1), Week 4, Week 8, Week 12, Week 16 and Week 48 visits. The timing of the interim visits between Week 16 and Week 48 depended on the patient's injection regimen, i.e. every 12 weeks (q12w) or every 8 weeks (q8w). Patients who consented and met all the inclusion and none of the exclusion criteria were screened to evaluate eligibility. After confirmation of eligibility, patients were included and treated with brolucizumab 6 mg. The maximum study duration for 1 patient was 48 weeks, including Screening. There were 2 periods in this study:

  • Open-label treatment period: from Screening/Baseline (Day 1) to Week 40/Week 44 (depending on assigned regimen)
  • Follow-up period: Week 40/Week 44 to Week 48

A Safety Review Committee (SRC) was established for this study to provide an independent, systematic, standardized and unbiased assessment of the review of intraocular inflammation (IOI), retinal vasculitis (RV) and/or retinal vascular occlusion (RO).

Being tested
RTH258/Brolucizumab
Keywords
age-related macular degeneration, wetAMD, nAMD, neovascular, choroidal neovascularization, CNV, OCT-angiography
Medical subject headings
Macular Degeneration, Choroidal Neovascularization

What participants receive

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

  • RTH258/BrolucizumabDrug

    Brolucizumab is a new generation of anti-VEGF (vascular endothelial growth factor). All patients were treated with brolucizumab 6mg: 3 loading injections (at Screening/Baseline, Week 4 and Week 8), followed by maintenance treatment every 8 weeks (Q8W) or every 12 weeks (Q12W) depending on disease activity from Week 16/Week20 to Week 40/Week 44.

    Brolucizumab was administered by an intravitreal (IVT) injection to the study. eye.

Study groups in NCT04239027
Study groupRoleWhat they receive
RTH258/BrolucizumabExperimentalThis is a single-arm study in which all patients will be treated with brolucizumab 6mg: 3 loading injections (at Screening/Baseline, Week 4 and Week 8), followed by maintenance treatment from Week 16/Week 20 up to Week 40/Week 44.
Receives: Drug: RTH258/Brolucizumab

What is being measured

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

  1. Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 12

    OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography.

    It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation.

    The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size.

    Inter-Quartile Range = q1 - q3.

    Measured: Baseline, Week 12

Secondary outcomes (12)

  1. Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48

    OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography.

    It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation.

    The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size.

    Measured: Baseline, Weeks 4, 8, 48

  2. Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48

    OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography.

    It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation.

    The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size.

    Measured: Baseline, Weeks 4, 8, 12, 48

  3. Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48

    OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography.

    It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation.

    The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size.

    Measured: Baseline, Week 48

  4. Change in Best Corrected Visual Acuity (BCVA) From Baseline up to Week 48

    BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.

    Visual Function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included.

    Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.

    Measured: Baseline, Weeks 4, 8, 12, 48

  5. Percentage of Patients Who Are Maintained on an Exclusive Treatment Interval Every 12 Weeks (q12w) Following the Loading Phase to Week 48

    To estimate the proportion of patients treated at q12w frequency with brolucizumab.

    Measured: Weeks 20, 32, 44, 48

  6. The Probability of the First q12w Interval for Determining Successful q12w Maintenance

    To estimate the predictive value of the first q12w cycle for maintenance of q12w treatment with brolucizumab via the Kaplan-Meier method.

    Measured: Weeks 0,4,5,8,9,15,16,17,18,20,21,22,24,32,33,34,35,40,41,43,44,48

  7. Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity

    To evaluate the time from last IVT injection in the initiation phase to first visit with no disease activity.

    The 95% CI are estimated by using the Greenwood formula Kaplan-Meier (KM) method.

    Measured: Week 8 until Week 41

  8. Change From Baseline up to Week 48 in SD-OCT Assessed by Qualitative and Quantitative Criteria: Central Sub-Field Retinal Thickness (CSFT)

    Central sub-field thickness (CSFT) was measured by Spectral Domain Optical Coherence Tomography (SD-OCT). The CSFT evaluated in this study represents the average retinal thickness of the circular area within 1 mm diameter around the foveal center. SD-OCT images were obtained and assessed in the study eye by SD-OCT machines. (i.e. no time-domain nor swept-source OCT).

    Measured: Baseline, Weeks 4, 8, 12, 48

  9. Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye

    To evaluate the effect of brolucizumab on anatomical parameters as assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) and Fluorescein Angiography (FA).

    RPE = Retinal Pigmented Epithelium IRF = Intraretinal Fluid SRF = Subretinal Fluid Sub-RPE = Sub Retinal Pigmented Epithelium

    Measured: Baseline, Weeks 4, 8, 12, 48

  10. Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab.

    An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

    Measured: Up to Week 48

  11. Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye

    An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

    Measured: Up to Week 48

  12. Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab - Non-Ocular Adverse Events

    An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

    Measured: Up to Week 48

Timeline

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

  1. First posted23 Jan 2020
  2. Study start26 Jan 2021
  3. Primary completion23 May 2022
  4. Study completion2 Feb 2023

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
Not applicable
Intervention model
Single group
Model description
Single-arm, open-label study
Masking
None (open label)
Enrolment
210 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04239027
Sponsor's protocol ID
CRTH258AFR01
Other IDs
2019-003338-17, 2019
Acronym
OCTOPUS
Status last verified
Oct 2024
First submitted
21 Jan 2020
Last updated
9 Oct 2024
Data monitoring committee
No
FDA-regulated drug
No
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

  • Bodaghi B, Souied EH, Tadayoni R, Weber M, Ponthieux A, Kodjikian L. Detection and Management of Intraocular Inflammation after Brolucizumab Treatment for Neovascular Age-Related Macular Degeneration. Ophthalmol Retina. 2023 Oct;7(10):879-891. doi: 10.1016/j.oret.2023.06.009. Epub 2023 Jun 19.

    PubMed 37343623

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing RTH258/Brolucizumab in people with Neovascular Age Related Macular Degeneration, run by Novartis Pharmaceuticals at 40 sites in France.

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 6 inclusion and 35 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 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in France. 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 4 Jun 2024). 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?

Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 12 (time frame: Baseline, Week 12). 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 NCT04239027, 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 9 Oct 2024.

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