Study of Brolucizumab in Adult Patients With Suboptimal Anatomically Controlled Neovascular Age-related Macular Degeneration

Neovascular Age-Related Macular Degeneration Clinical Trial

— SWIFT  

Official title:

A One-year, Single-arm, Open-label, Multicenter Study Assessing the Effect of Brolucizumab on Disease Control in Adult Patients With Suboptimal Anatomically Controlled Neovascular Age-related Macular Degeneration (SWIFT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04264819
• Other study ID #: CRTH258AFR03
• Secondary ID: 2019-004145-33
• Status: Completed
• Phase: Phase 3
• Start date: December 14, 2020
• Est. completion date: May 10, 2023

Study information

• Verified date: July 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

The safety and efficacy of brolucizumab were assessed in 2 randomized, multicenter, double-masked, active treatment-controlled Phase 3 studies in nAMD patients (the HAWK study (RTH258-C001 [NCT02307682]) and the HARRIER study (RTH258-C002 [NCT02434328]). Accordingly, a new Phase 3b study (TALON, CRTH258A2303) is being conducted to evaluate the efficacy and safety of brolucizumab in a Treat-to-Control (TtC) regimen for the treatment of naïve patients with nAMD. In this TtC regimen, patients receive 3 consecutive injections every 4 weeks and then the injection interval is extended by 4 weeks up to a maximum of a 16-week interval. The decision to extend or reduce the injection interval is taken by the Investigator at each visit based on his/her judgment of disease activity, according to the patient visual and/or anatomic outcomes. If there is no disease activity, the injection interval can be extended by 4 weeks ; if disease activity occurs or recurs, the injection interval should be shortened accordingly by 4 weeks at a time or to a minimal interval of 8 weeks. The injection interval can also be maintained if the Investigator deems that the patient do not benefit from injection interval adjustment.

Since all these studies were conducted in a naïve nAMD patient population, no data are available on the efficacy and safety of brolucizumab in pretreated nAMD patients who still present active exudation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: May 10, 2023
• Est. primary completion date: October 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

1. Patients must provide written informed consent before any study-related procedures are performed.

2. Patients must be 50 years of age or older at Screening/Baseline.

Study eye:

3. Active CNV lesions secondary to nAMD diagnosed < 18 months prior to Screening/Baseline that affect the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by FA and sequelae of CNV, e.g. pigment epithelial detachment (PED), subretinal hemorrhage or sub RPE hemorrhage, blocked fluorescence, or macular edema.

4. Previous treatment with only one licensed anti-VEGF drug (i.e. Lucentis®, Eylea®) with a = Q4 and = Q8 treatment (treatment interval of 26 to 62 days inclusive) with licensed anti-VEGF (a minimal washout period of at least 4 weeks / 26 days is required). Patients must have received at least 3 injections of this anti-VEGF in the 6 months prior to Screening/Baseline.

5. Presence of residual fluid (IRF or SRF that affects the central subfield under, as seen by OCT)

6. BCVA score must be = 83 and = 38 letters at an initial testing distance of 4 meters starting distance using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts at Screening/Baseline.

Exclusion Criteria:

Ocular conditions

1. 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.

2. Presence of amblyopia, amaurosis, or ocular disorders in the fellow eye with BCVA < 35 ETDRS letters at Screening/Baseline (except when due to conditions whose surgery may improve visual acuity, e.g. cataract).

3. Medical history of intraocular inflammation and/or retinal vascular occlusion within 12 months prior to Screening/Baseline

Study eye

4. Poor quality of OCT image at Screening/Baseline.

5. Atrophy or fibrosis involving the center of the fovea in the study eye, as assessed by CFP and fundus autofluorescence (FAF).

6. The total area of fibrosis or subretinal blood affecting the foveal center point comprising = 50% of the lesion area in the study eye.

7. 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.

8. Structural damage within 0.5 disc diameter of the center of the macula in the study eye, e.g. vitreomacular traction, epiretinal membrane, RPE rip/tear scar, laser burn, at the time of Screening/Baseline that in the Investigator's opinion could preclude visual function improvement with treatment.

9. Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Screening/Baseline.

10. Uncontrolled glaucoma in the study eye defined as IOP > 25 mmHg on medication or according to the Investigator's judgment, at Screening/Baseline.

11. Aphakia and/or absence of the posterior capsule in the study eye. Ocular treatments (study eye)

12. Patient has received any investigational treatment for nAMD (other than vitamin supplements) in the study eye at any time.

13. Previous use of intraocular or periocular of corticosteroids in the study eye within the 6 month period prior to Screening/Baseline.

14. Previous penetrating keratoplasty or vitrectomy at any time prior to Screening/Baseline.

15. 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 and peripheral laser photocoagulation.

• Previous macular surgery or other intraocular surgical intervention

16. Previous laser treatment for nAMD including photodynamic therapy (PDT) laser at any time prior to Screening/Baseline.

17. Previous treatment with investigational drugs.

Systemic conditions or treatments

18. End-stage renal disease requiring dialysis or renal transplant.

19. 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 Baseline, except temporary use for COVID-19 treatment.

20. 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 Baseline. Note: observational clinical studies solely involving over-the-counter vitamins, supplements, or diets are not exclusionary.

21. Systemic anti-VEGF therapy at any time.

22. Stroke or myocardial infarction in the 6-month period prior to Screening/Baseline.

23. Uncontrolled blood pressure defined as a systolic value = 160 mmHg or diastolic value = 100 mmHg. (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).

24. 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.

25. 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.

26. History of hypersensitivity to the study drug or its excipients or to drugs of similar classes, or clinically relevant sensitivity to fluorescein dye, as assessed by the Investigator.

Other

27. 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.

28. Women of childbearing potential, defined as all women less than 1 year postmenopausal or less than 6 weeks since sterilization.

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.

29. 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.)

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-Related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• RTH258/Brolucizumab
Brolucizumab is a new generation of anti-VEGF (vascular endothelial growth factor). All patients will be treated with brolucizumab 6mg: 3 loading injections (at Screening/Baseline, Week 4 and Week 8), followed by Treat-to-Control regimen up to Week 44/46.

Locations

Country	Name	City	State
France	Novartis Investigative Site	Aix en Provence
France	Novartis Investigative Site	Angers
France	Novartis Investigative Site	Avignon
France	Novartis Investigative Site	Bobigny cedex	Seine Saint Denis
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Caen Cedex
France	Novartis Investigative Site	Colmar Cedex
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	La Rochelle
France	Novartis Investigative Site	La Valette Du Var
France	Novartis Investigative Site	Le Chesnay
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Lyon cedex 04	Rhone
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Melun
France	Novartis Investigative Site	Montargis
France	Novartis Investigative Site	Montauban
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Mulhouse cedex
France	Novartis Investigative Site	Nantes
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Nice	Cedex1
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris cedex 10
France	Novartis Investigative Site	Paris Cedex 13
France	Novartis Investigative Site	Perpignan
France	Novartis Investigative Site	Plerin
France	Novartis Investigative Site	Poitiers
France	Novartis Investigative Site	Rennes Cedex 9	FRA
France	Novartis Investigative Site	Rouen
France	Novartis Investigative Site	Rueil Malmaison
France	Novartis Investigative Site	Saint Cyr sur Loire	Indre Et Loire
France	Novartis Investigative Site	Saint Herblain
France	Novartis Investigative Site	Saint Jean de Vedas
France	Novartis Investigative Site	Saint Martin des Champs
France	Novartis Investigative Site	Saint-Jean
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Toulouse Cedex 9
France	Novartis Investigative Site	Tours
France	Novartis Investigative Site	Vincennes

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with no disease activity at Week 16	To evaluate the effect of brolucizumab 6 mg on disease control	Week 16
Secondary	Proportion of patients with no disease activity at Week 48	To evaluate the long term effects of brolucizumab 6 mg on disease control	Week 48
Secondary	Change from Baseline in CFST (Central Sub-Field Retinal Thickness) as assessed by OCT (Optical Coherence Tomography) over time up to Week 48	To evaluate the effect of brolucizumab 6 mg on anatomical parameters	Week 48
Secondary	Absence of IRF (Intraretinal Fluid), SRF (Subretinal Fluid), and sub-RPE (Retinal Pigmented Epithelium) fluid as assessed by OCT over time up to Week 48	To evaluate the effect of brolucizumab 6 mg on anatomical parameters	Week 48
Secondary	Proportion of patients with a dry retina (neither IRF nor SRF) up to Week 48	To evaluate the effect of brolucizumab 6 mg on anatomical parameters	Week 48
Secondary	Distribution of the last interval with no disease activity up to Week 48	To evaluate the durability of brolucizumab 6 mg	Week 48
Secondary	Distribution of the maximal intervals with no disease activity up to Week 48	To evaluate the durability of brolucizumab 6 mg	Week 48
Secondary	Average change in BCVA (Best-Corrected Visual Acuity) from Baseline up to Week 48	To evaluate functional outcomes	Week 48