Study to Assess the Efficacy and Safety of Brolucizumab 6mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen (TALON)

NCT04005352 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CRTH258A23032019-000716-28
• Study Type: interventional
• Target: 734
• Locations: 19 countries
• Sites: 116

Brief Summary

This was a 64-week randomized, double-masked, multi-center, active-controlled, two-arm study in patients with neovascular age related macular degeneration (nAMD) who have not previously received anti- vascular endothelial growth factor (VEGF) treatment.

Conditions

Age-related Macular Degeneration

Keywords

Age-related Macular Degeneration; Macular Degeneration; Wet Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; AMD; nAMD; wet AMD; RTH258; Brolucizumab; double blind; age-related macular degeneration (ARMD); vision loss; macula damage; retina damage; dry macular degeneration; Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration

Outcome Measures

Primary Outcomes (2)

• Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye

  No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. Intraretinal Fluid (IRF), Subretinal Fluid (SRF), hemorrhage, leakage, etc.). Treatment interval distribution. Number (%) of subjects at 12/8/4-weeks intervals up to Week 32 for the study eye. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or ≥12-week then the floor value of these ranges was used.

  Up to Week 32

• Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye

  BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 28 and 32 combined.

  Baseline, Week 28 and Week 32

Secondary Outcomes (25)

• Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye

  Up to Week 64

• Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye

  Up to Week 64

• Number of Participants With no Disease Activity - Study Eye

  Weeks 14 and 16

• Time From Last Loading Injection to First Visit With No Disease Activity (Weeks) - 75th Percentile - Study Eye

  Up to Week 64

• Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye

  Up to Week 64

Study Arms (2)

Brolucizumab 6 mg

EXPERIMENTAL

3 x 4-week injections and one 8-week Intra-vitreal injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62.

Biological: Brolucizumab 6 mg

Aflibercept 2 mg

ACTIVE COMPARATOR

3 x 4-week injections and one 8-week Intra-vitreal injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62

Biological: Aflibercept 2 mg

Interventions

Brolucizumab 6 mg BIOLOGICAL

Intra-vitreal injection

Also known as: RTH258

Brolucizumab 6 mg

Aflibercept 2 mg BIOLOGICAL

Intra-vitreal injection

Also known as: EYLEA

Aflibercept 2 mg

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study
• Male or female patients ≥ 50 years of age at screening who are treatment naive
• Active choroidal neovascularization (CNV) secondary to AMD that affects 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 or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema (study eye)
• Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) that affects the central subfield, as seen by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye)
• Best-corrected visual acuity (BCVA) score between 83 and 38 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at both screening and baseline visit (study eye)

You may not qualify if:

• Ocular conditions/disorders at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the first 12-month study period, structural damage of the fovea, atrophy or fibrosis at the center of the fovea (study eye)
• Any active intraocular or periocular infection or active intraocular inflammation, at screening or baseline (study eye)
• Uncontrolled glaucoma defined as intraocular pressure (IOP) \> 25 mmHg on medication, or according to investigator's judgment, at screening or baseline (study eye)
• Ocular treatments: previous treatment with any anti-vascular endothelial growth factor (VEGF) drugs or investigational drugs, intraocular or periocular steroids, macular laser photocoagulation, photodynamic therapy, vitreoretinal surgery, intraocular surgery (study eye)
• Stroke or myocardial infarction during the 6-month period prior to baseline
• Systemic anti-VEGF therapy at any time.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (118)

Novartis Investigative Site

Phoenix, Arizona, 85020, United States

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Novartis Investigative Site

Huntington Beach, California, 92647, United States

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Novartis Investigative Site

Loma Linda, California, 92354, United States

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Novartis Investigative Site

Riverside, California, 92505, United States

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Novartis Investigative Site

Santa Ana, California, 92705, United States

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Novartis Investigative Site

Fort Lauderdale, Florida, 33309, United States

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Novartis Investigative Site

Fort Myers, Florida, 33912-7125, United States

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Novartis Investigative Site

Orlando, Florida, 32789, United States

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Pinellas Park, Florida, 33782, United States

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Winter Haven, Florida, 33880, United States

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Springfield, Illinois, 62704, United States

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Indianapolis, Indiana, 46280, United States

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West Des Moines, Iowa, 50266, United States

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Minneapolis, Minnesota, 55435, United States

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Hickory, North Carolina, 28602, United States

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Portland, Oregon, 97210, United States

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Springfield, Oregon, 97477, United States

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Germantown, Tennessee, 38138, United States

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Austin, Texas, 78705, United States

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Bellaire, Texas, 77401, United States

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Novartis Investigative Site

Fort Worth, Texas, 76104, United States

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Novartis Investigative Site

Houston, Texas, 77025, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

San Antonio, Texas, 78240, United States

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Novartis Investigative Site

Caba, Buenos Aires, 1116, Argentina

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Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO, Argentina

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Rosario, De Santa Fe, B7602, Argentina

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Novartis Investigative Site

Caba, C1056, Argentina

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Albury, New South Wales, 2640, Australia

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Hurstville, New South Wales, 2220, Australia

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Parramatta, New South Wales, 2150, Australia

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Sydney, New South Wales, 2000, Australia

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Southport, Queensland, 4215, Australia

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Glen Waverley, Victoria, 3150, Australia

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Rowville, Victoria, 3179, Australia

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Nedlands, Western Australia, 6009, Australia

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Vienna, 1090, Austria

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Vienna, 1140, Austria

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Alken, 3570, Belgium

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Leuven, 3000, Belgium

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Brampton, Ontario, L6Y 0P6, Canada

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London, Ontario, N6A 4G5, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Boisbriand, Quebec, J7H 1S6, Canada

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Québec, Quebec, G1S 4L8, Canada

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Novartis Investigative Site

Zlín, Czech Republic, 762 75, Czechia

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Hradec Králové, CZE, 500 05, Czechia

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Novartis Investigative Site

Ostrava Poruba, 708 52, Czechia

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Prague, 100 34, Czechia

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Prague, 12808, Czechia

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Novartis Investigative Site

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

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Lyon, Rhone, 69317, France

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Bordeaux, 33000, France

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Créteil, 94000, France

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Marseille, F 13008, France

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Montauban, 82000, France

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Nantes, 44093, France

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Paris, 75010, France

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Paris, 75015, France

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Rueil-Malmaison, 92500, France

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Strasbourg, 67000, France

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Berlin, 10713, Germany

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Bonn, 53105, Germany

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Düsseldorf, 40212, Germany

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Freiburg im Breisgau, 79106, Germany

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Göttingen, 37075, Germany

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Kempten, 87435, Germany

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Leipzig, 04103, Germany

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Mainz, 55131, Germany

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Münster, 48145, Germany

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Münster, 48149, Germany

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Ulm, 89075, Germany

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Jerusalem, 9112001, Israel

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Ramat Gan, 52621, Israel

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Tel Aviv, 64239, Israel

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Ẕerifin, 6093000, Israel

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Bologna, BO, 40138, Italy

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Genova, GE, 16132, Italy

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Milan, MI, 20100, Italy

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Milan, MI, 20122, Italy

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Palermo, PA, 90127, Italy

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Perugia, PG, 06100, Italy

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Novara, 28100, Italy

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Malacca, Melaka Malaysia, 75000, Malaysia

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Novartis Investigative Site

Batu Caves, Selangor, 68100, Malaysia

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Shah Alam, Selangor, 40000, Malaysia

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's-Hertogenbosch, 5200, Netherlands

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Nijmegen, 6525 EX, Netherlands

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Coimbra, 3000 075, Portugal

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Porto, 4099-001, Portugal

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Novartis Investigative Site

Vila Franca de Xira, 2600-009, Portugal

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Novartis Investigative Site

Bundang Gu, Gyeonggi-do, 13620, South Korea

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Seoul, Seocho Gu, 06591, South Korea

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Busan, 49241, South Korea

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Daegu, 705703, South Korea

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Seoul, 05505, South Korea

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Novartis Investigative Site

Seoul, 07301, South Korea

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Novartis Investigative Site

Barcelona, Catalonia, 08022, Spain

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Novartis Investigative Site

Sant Cugat del Vallès, Catalonia, 08190, Spain

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Novartis Investigative Site

Pamplona, Navarre, 31008, Spain

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Burjassot, Valencia, 46100, Spain

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Novartis Investigative Site

Barcelona, 08024, Spain

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Novartis Investigative Site

Barcelona, 08025, Spain

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Novartis Investigative Site

Córdoba, 14012, Spain

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Novartis Investigative Site

Zaragoza, 50009, Spain

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Novartis Investigative Site

Örebro, 701 85, Sweden

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Novartis Investigative Site

Västerås, 72189, Sweden

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Binningen, 4102, Switzerland

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Novartis Investigative Site

Taipei, 103616, Taiwan

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Novartis Investigative Site

Taipei, 10449, Taiwan

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Novartis Investigative Site

Taipei, 11217, Taiwan

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Novartis Investigative Site

Taoyuan District, 33305, Taiwan

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Novartis Investigative Site

Bradford, West Yorkshire, BD9 6RJ, United Kingdom

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Novartis Investigative Site

London, EC1V 2PD, United Kingdom

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Novartis Investigative Site

Rugby, CV22 5PX, United Kingdom

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Novartis Investigative Site

Sunderland, SR2 9HP, United Kingdom

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Novartis Investigative Site

Torquay, TQ2 7AA, United Kingdom

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Novartis Investigative Site

Wolverhampton, WV10 0QP, United Kingdom

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Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Macular Degeneration; Wet Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Vision Disorders; Geographic Atrophy; Choroidal Neovascularization

Interventions

brolucizumab; aflibercept

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double arm, multi-center

Study Record Dates

• First Submitted: July 1, 2019
• First Posted: July 2, 2019
• Study Start: September 25, 2019
• Primary Completion: September 9, 2022
• Study Completion: September 9, 2022
• Last Updated: October 9, 2024
• Results First Posted: January 30, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CZ (5); AR (4); CA (5); NL (2); ES (8); MY (3); SE (2); IL (4); FR (11); DE (11); AU (8); IT (7); PT (3); KR (6); CH (1); US (24); TW (4); BE (2); GB (6)