Phase III Study Assessing the Efficacy, Safety and Immunogenicity of SOK583A1 Versus Eylea® in Patients With Neovascular Age-related Macular Degeneration (Mylight)

A 52-week Multicenter, Randomized, Double-masked, 2-arm Parallel Study to Compare Efficacy, Safety and Immunogenicity of SOK583A1 to Eylea®, Administered Intravitreally, in Patients With Neovascular Age-related Macular Degeneration

Purpose and rationale: To demonstrate similar efficacy, safety and immunogenicity of SOK583A1 and Eylea EU as per Eylea approved treatment regimen in patients with nAMD.

The primary clinical question of interest is: Does SOK583A1 have similar efficacy as Eylea EU in terms of mean change in BCVA score in participants with nAMD who are anti-VEGF naive, without important protocol deviations and adherent to the treatment and completed the treatment to Week 8?

Study Overview

• Status: Completed
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Biological: SOK583A1 (40 mg/mL); Biological: Eylea EU (40 mg/mL)

Detailed Description

BCVA: Best-Corrected Visual Acuity Eylea EU: Europe-authorized Eylea® nAMD: Neovascular Age-related Macular Degeneration VEGF: Vascular Endothelium Growth Factor

• Study Type: Interventional
• Enrollment (Actual): 485
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sandoz; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Sandoz; Phone Number: +41613241111

Study Locations

• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Sandoz Investigational Site
    • Liverpool, New South Wales, Australia, 2170
      • Sandoz Investigational Site
    • Parramatta, New South Wales, Australia, 2150
      • Sandoz Investigational Site
    • Sydney, New South Wales, Australia, 2000
      • Sandoz Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Sandoz Investigational Site
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Sandoz Investigational Site
• Austria
  • Graz, Austria, A-8036
    • Sandoz Investigational Site
  • Oberoesterreich
    • Linz, Oberoesterreich, Austria, A 4020
      • Sandoz Investigational Site
  • Upper Austria
    • Linz, Upper Austria, Austria, 4021
      • Sandoz Investigational Site
• Bulgaria
  • Sofia, Bulgaria, 1784
    • Sandoz Investigational Site
• Czechia
  • Pardubice, Czechia, 530 02
    • Sandoz Investigational Site
  • Praha, Czechia, 12808
    • Sandoz Investigational Site
  • Praha 5, Czechia, 150 00
    • Sandoz Investigational Site
• France
  • Paris, France, 75015
    • Sandoz Investigational Site
  • Bouches-Du-Rhone
    • Marseille, Bouches-Du-Rhone, France, 13008
      • Sandoz Investigational Site
  • Indre Et Loire
    • Saint Cyr sur Loire, Indre Et Loire, France, 37540
      • Sandoz Investigational Site
• Germany
  • Duesseldorf, Germany, 40212
    • Sandoz Investigational Site
  • Frankfurt Am Main, Germany, 60596
    • Sandoz Investigational Site
  • Freiburg, Germany, 79106
    • Sandoz Investigational Site
  • Hannover, Germany, 30625
    • Sandoz Investigational Site
  • Leipzig, Germany, 04103
    • Sandoz Investigational Site
  • Mainz, Germany, 55131
    • Sandoz Investigational Site
  • Marburg, Germany, 35043
    • Sandoz Investigational Site
• Hungary
  • Budapest, Hungary, H-1085
    • Sandoz Investigational Site
  • Budapest, Hungary, H-1136
    • Sandoz Investigational Site
  • Debrecen, Hungary, 4032
    • Sandoz Investigational Site
  • Sopron, Hungary, H-9400
    • Sandoz Investigational Site
  • Szeged, Hungary, H-6720
    • Sandoz Investigational Site
  • Szekesfehervar, Hungary, H-8000
    • Sandoz Investigational Site
  • HUN
    • Budapest, HUN, Hungary, 1204
      • Sandoz Investigational Site
  • Pest Megye
    • Budapest, Pest Megye, Hungary, 1134
      • Sandoz Investigational Site
• Israel
  • Haifa, Israel, 3434104
    • Sandoz Investigational Site
  • Jerusalem, Israel, 9112001
    • Sandoz Investigational Site
  • Kfar Saba, Israel, 44281
    • Sandoz Investigational Site
  • Lod, Israel, 6093000
    • Sandoz Investigational Site
  • Petach Tikva, Israel, 4941492
    • Sandoz Investigational Site
  • Rehovot, Israel, 7610001
    • Sandoz Investigational Site
  • Tel Aviv, Israel, 6423906
    • Sandoz Investigational Site
• Japan
  • Aichi
    • Nagakute-city, Aichi, Japan, 480-1195
      • Sandoz Investigational Site
    • Nagoya, Aichi, Japan, 457 8510
      • Sandoz Investigational Site
    • Nagoya, Aichi, Japan, 466 8560
      • Sandoz Investigational Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Sandoz Investigational Site
  • Hiroshima
    • Kure, Hiroshima, Japan, 737-0029
      • Sandoz Investigational Site
  • Hyogo
    • Amagasaki city, Hyogo, Japan, 660 8550
      • Sandoz Investigational Site
    • Kobe-shi, Hyogo, Japan, 650-0017
      • Sandoz Investigational Site
  • Ibaraki
    • Inashiki-gun, Ibaraki, Japan, 300-0395
      • Sandoz Investigational Site
  • Kagoshima
    • Kagoshima city, Kagoshima, Japan, 890 8520
      • Sandoz Investigational Site
  • Shizuoka
    • Hamamatsu-city, Shizuoka, Japan, 430-8558
      • Sandoz Investigational Site
  • Tokyo
    • Meguro-ku, Tokyo, Japan, 152-8902
      • Sandoz Investigational Site
    • Taito-ku, Tokyo, Japan, 111-0051
      • Sandoz Investigational Site
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-8505
      • Sandoz Investigational Site
• Latvia
  • Riga, Latvia, 1002
    • Sandoz Investigational Site
  • Riga, Latvia, LV-1007
    • Sandoz Investigational Site
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Sandoz Investigational Site
  • Kauno Apskritis
    • Kaunas, Kauno Apskritis, Lithuania, 50161
      • Sandoz Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-631
    • Sandoz Investigational Site
  • Lodz, Poland, 91-134
    • Sandoz Investigational Site
  • Lublin, Poland, 20-079
    • Sandoz Investigational Site
  • Wroclaw, Poland, 53-334
    • Sandoz Investigational Site
  • Malopolska
    • Krakow, Malopolska, Poland, 30-394
      • Sandoz Investigational Site
• Portugal
  • Coimbra, Portugal, 3000-548
    • Sandoz Investigational Site
  • Coimbra, Portugal, 3030-363
    • Sandoz Investigational Site
  • Porto, Portugal, 4200 319
    • Sandoz Investigational Site
• Slovakia
  • Bratislava, Slovakia, 821 01
    • Sandoz Investigational Site
  • Bratislava, Slovakia, 83301
    • Sandoz Investigational Site
  • Trencin, Slovakia, 91171
    • Sandoz Investigational Site
  • Slovak Republic
    • Zilina, Slovak Republic, Slovakia, 010 01
      • Sandoz Investigational Site
• Spain
  • Barcelona, Spain, 08021
    • Sandoz Investigational Site
  • Barcelona, Spain, 8022
    • Sandoz Investigational Site
  • Zaragoza, Spain, 50009
    • Sandoz Investigational Site
  • Asturias
    • Oviedo, Asturias, Spain, 33012
      • Sandoz Investigational Site
  • Catalunya
    • Sant Cugat, Catalunya, Spain, 08190
      • Sandoz Investigational Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Sandoz Investigational Site
  • Pais Vasco
    • Bilbao, Pais Vasco, Spain, 48006
      • Sandoz Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85021
      • Sandoz Investigational Site
  • California
    • Arcadia, California, United States, 91006
      • Sandoz Investigational Site
    • Campbell, California, United States, 95008
      • Sandoz Investigational Site
    • Encino, California, United States, 91436
      • Sandoz Investigational Site
    • Fullerton, California, United States, 92835
      • Sandoz Investigational Site
    • Glendale, California, United States, 91203
      • Sandoz Investigational Site
    • Huntington Beach, California, United States, 92647
      • Sandoz Investigational Site
    • Pasadena, California, United States, 91107
      • Sandoz Investigational Site
    • Poway, California, United States, 92064
      • Sandoz Investigational Site
    • Redlands, California, United States, 92374
      • Sandoz Investigational Site
    • Sacramento, California, United States, 95841
      • Sandoz Investigational Site
  • Florida
    • Fort Myers, Florida, United States, 33912-7125
      • Sandoz Investigational Site
    • Pinellas Park, Florida, United States, 33782
      • Sandoz Investigational Site
    • Plantation, Florida, United States, 33324
      • Sandoz Investigational Site
    • Stuart, Florida, United States, 34994
      • Sandoz Investigational Site
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Sandoz Investigational Site
  • Illinois
    • Oak Forest, Illinois, United States, 60452
      • Sandoz Investigational Site
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Sandoz Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Sandoz Investigational Site
  • New York
    • Great Neck, New York, United States, 11021
      • Sandoz Investigational Site
    • Liverpool, New York, United States, 13088
      • Sandoz Investigational Site
    • Rochester, New York, United States, 14620
      • Sandoz Investigational Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Sandoz Investigational Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Sandoz Investigational Site
  • Texas
    • Abilene, Texas, United States, 79606
      • Sandoz Investigational Site
    • Arlington, Texas, United States, 76012
      • Sandoz Investigational Site
    • Willow Park, Texas, United States, 76087
      • Sandoz Investigational Site
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Sandoz Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Participants eligible for inclusion in this study must meet all of the following criteria:

1. Signed informed consent must be obtained prior to participation in the study
2. Participants must be 50 years of age or older at Screening
3. Anti-VEGF treatment-naive patients for either eye and systemically
4. Study eye diagnosed with active CNV lesions (type 1 and/ or type 2) secondary to AMD and/or Retinal Angiomatous Proliferation lesions (type 3), affecting the central subfield. Active CNV lesion is defined by the presence of leakage as evidenced by fluorescein angiography, and intra- or subretinal fluid as evidenced by optical coherence tomography, both confirmed by the CRC at Screening
5. Total area of CNV (including both classic and occult components) must comprise > 50% of the total lesion area in the study eye, confirmed by the CRC at Screening
6. BCVA between 73 and 38 letters, both inclusive, in the study eye at Screening and Baseline using ETDRS testing charts
7. Willing and able to comply with all study procedures, and be likely to complete the study
8. Clear ocular media and adequate pupil dilatation in both eyes to permit good quality photographic imaging.

Participants meeting any of the following criteria are not eligible for inclusion in this study.

Ocular conditions and treatments:

1. Previous treatment with any anti-VEGF therapy in either eye or investigational drugs in study eye or fellow eye, at any time prior to Baseline
2. Participant has received any approved treatment for nAMD (other than vitamin and dietary supplements) in the study eye and at any time prior to Baseline
3. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of -8 diopters or more negative), ocular histoplasmosis syndrome, angioid streaks,choroidal rupture, or multifocal choroiditis in the study eye, assessed by imaging at screening by CRC and appropriately stated in the multi-modal eligibility confirmation report
4. Any active or suspected intraocular or periocular infection or suspected active intraocular inflammation (e.g infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in either eye at Screening or Baseline
5. Subfoveal fibrosis, atrophy, or scarring extending > 50% of total lesion area in the study eye as assessed by the Investigator at Screening and confirmed by the CRC prior to randomization
6. Subretinal hemorrhage that is ≥ 50% of the total lesion area in the study eye, or if the subretinal hemorrhage involving the fovea is 1 or more disc areas (≥ 2.54 mm2 ) in size in the study eye, as assessed by Fluorescein Angiography (FA) and confirmed by the CRC
7. Retinal pigment epithelium (RPE) rip/tear in the study eye at Screening or Baseline
8. Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline

9. History or evidence of the following, in the study eye:

   • Intraocular (including cataract surgery) or refractive surgery within the 90 day period prior to Baseline. The yttrium aluminum garnet (YAG) posterior capsulotomy is allowed no later than 4 weeks prior to Baseline
   • Previous penetrating keratoplasty or vitrectomy
   • Previous panretinal photocoagulation
   • Previous photodynamic therapy
   • Previous submacular surgery or other surgical intervention for AMD
   • Retinal detachment or treatment or surgery for retinal detachment
   • Any history of macular hole of stage 2 and above
   • Prior trabeculectomy or other filtration surgery
   • Ocular trauma within the 6-months period prior to Baseline
10. History of hypersensitivity to any of the study treatments or its excipients, or clinically relevant sensitivity to fluorescein dye, as assessed by the Investigators
11. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication or according to Investigator's judgment at Screening or Baseline
12. Aphakia and/or absence of the posterior capsule in the study eye at Screening or Baseline, unless it occurred as a result of a YAG posterior capsulotomy in association with prior posterior chamber intraocular lens implantation
13. Intra or periocular use of corticosteroids in the study eye within a 6 month period prior to Baseline
14. Use of topical ocular corticosteroids in the study eye for 30 or more consecutive days within the 90 days period prior to Baseline
15. Previous therapeutic radiation near the region of the study eye
16. Concomitant conditions or ocular disorders in the study eye, including media opacities, cataract and diabetic macular edema, at Screening or Baseline which could, in the opinion of the Investigator, prevent response to study treatment or may confound interpretation of study results (efficacy and safety), compromise visual acuity or require medical or surgical intervention during the course of the study
17. Presence of amblyopia, amaurosis or ocular disorders with BCVA <38 letters (ETDRS testing charts) in the fellow eye at Screening (except when due to conditions whose surgery may improve VA, e.g. cataract)
18. Presence of Scleromalacia in either eye

19. Participants requiring anti-VEGF treatment of the fellow eye at Baseline will not be eligible for the PK substudy

    Systemic conditions and treatments:

20. Previous systemic treatment with any anti-VEGF therapy
21. Use of systemic corticosteroids for 30 or more consecutive days within the 90 days prior to Baseline, with the exception of low stable doses of corticosteroids (defined as ≤ 10 mg prednisolone or equivalent dose used for 90 days or more).
22. Uncontrolled blood pressure defined as a systolic value ≥ 160 mmHg or diastolic value ≥ 100 mmHg at Screening
23. Stroke or myocardial infarction during the 6-month period prior to Baseline
24. Participation in an investigational systemic drug, biologic, or device study within 30 days or 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
25. Presence of infection at screening or active infection within 2 weeks before screening
26. Underlying advanced, severe and uncontrolled concomitant condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, inflammatory, infectious or gastrointestinal), physical examination finding, or clinical laboratory finding which in the opinion of the Investigator place the participant at unacceptable risk from participation in the study
27. History of a medical condition (including, but not limited to chronic disease immunosuppression, metabolic dysfunction, prior exposure to other drugs that may pose risk of infection or allergic reactions) that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product, or that might affect participant safety or interpretation of the study results.

28. Pregnant or nursing (lactating) women and women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 3 months after stopping the medication. Highly effective contraception methods include:

    • Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
    • Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
    • Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOK583A1 (40 mg/mL); Intravitreal (IVT) administration of 2 mg of SOK583A1 in the study eye, every 4 weeks (q4w) at Baseline, Week 4 and Week 8, and thereafter every 8 weeks (q8w) at week 16, 24, 32, 40 and 48.	Biological: SOK583A1 (40 mg/mL); IVT administration of 2 mg of SOK583A1 in the study eye, every 4 weeks (q4w) at Baseline, Week 4 and Week 8, and thereafter every 8 weeks (q8w) at week 16, 24, 32, 40 and 48.
Active Comparator: Eylea EU (40 mg/mL); IVT administration of 2 mg of Eylea EU in the study eye, every 4 weeks (q4w) at Baseline, Week 4 and Week 8, and thereafter every 8 weeks (q8w) at week 16, 24, 32, 40 and 48. EU: European	Biological: Eylea EU (40 mg/mL); IVT administration of 2 mg of Eylea EU in the study eye, every 4 weeks (q4w) at Baseline, Week 4 and Week 8, and thereafter every 8 weeks (q8w) at week 16, 24, 32, 40 and 48.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best-Corrected Visual Acuity (BCVA) Will be Assessed Using the ETDRS Testing Charts at an Initial Distance of 4 Meters. The Change From Baseline in BCVA in Letters is Defined as Difference Between BCVA Score Between Week 8 and Baseline.	The primary aim of the study is to demonstrate equivalence of change in BCVA score from Baseline at Week 8 between participants with nAMD treated with SOK583A1 and participants treated with Eylea EU. The primary analysis will be performed on the Per-Protocol Set (PPS), which is the most appropriate analysis set to use when testing for equivalence. ETDRS: Early Treatment Diabetic Retinopathy Study EU: European	Change from baseline in mean BCVA score at Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Similarity in the Anatomical Outcome Between SOK583A1 and Eylea EU	Mean change in CSFT using SD-OCT from Baseline to Week 1, 4, 8, 24 and 52 CSFT: Central Subfield Thickness SD-OCT: Spectral-Domain Optical Coherence Tomography	Week 1, 4, 8, 24 and 52
Similarity in the Anatomical Outcome Between SOK583A1 and Eylea EU	Mean change of CNV lesion size using FA from Screening to Week 8 and 52 CNV: Choroidal neovascularization FA: Fundus Angiography	Week 8 and 52
Similarity of Efficacy Between SOK583A1 and Eylea EU in Terms of BCVA	Mean change from Baseline in BCVA score using EDTRS testing charts at Week 24 and 52	Week 24 and 52
Similarity Between SOK583A1 and Eylea EU in Terms of Safety	Number and proportion of subjects with ocular and non-ocular Adverse Events (AEs) over 52 weeks including serious AEs, regardless of relationship to study treatment	52 weeks
Similarity Between SOK583A1 and Eylea EU in Terms of Immunogenicity	Development of binding and neutralizing Anti-drug antibodies (ADAs) up to Week 52	Week 52
Systemic Exposure to SOK583A1 and Eylea EU in Participants of the Pharmacokinetic (PK) Assessment	Aflibercept concentration assessments at Baseline (pre-dose) and 24 hours after the first and third injections	Baseline (pre-dose) and 24 hours after the first injection (day 2) and third injection (day 58)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis Systemic VEGF Concentrations in Patients Treated With Aflibercept	Mean VEGF concentrations	Assessment at Week 48 (pre-dose) and Week 52

Collaborators and Investigators

• Sponsor: Sandoz

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Actual): July 7, 2022
• Study Completion (Actual): May 10, 2023

Study Registration Dates

• First Submitted: April 15, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: CSOK583A12301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No