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

Neovascular Age-related Macular Degeneration Clinical Trial

— Mylight  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04864834
• Other study ID #: CSOK583A12301
• Status: Completed
• Phase: Phase 3
• Start date: May 12, 2021
• Est. completion date: May 10, 2023

Study information

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

Clinical Trial Summary

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?

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 485
• Est. completion date: May 10, 2023
• Est. primary completion date: July 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Sandoz Investigational Site	Adelaide	South Australia
Australia	Sandoz Investigational Site	Albury	New South Wales
Australia	Sandoz Investigational Site	Liverpool	New South Wales
Australia	Sandoz Investigational Site	Melbourne	Victoria
Australia	Sandoz Investigational Site	Parramatta	New South Wales
Australia	Sandoz Investigational Site	Sydney	New South Wales
Austria	Sandoz Investigational Site	Graz
Austria	Sandoz Investigational Site	Linz	Oberoesterreich
Austria	Sandoz Investigational Site	Linz	Upper Austria
Bulgaria	Sandoz Investigational Site	Sofia
Czechia	Sandoz Investigational Site	Pardubice
Czechia	Sandoz Investigational Site	Praha
Czechia	Sandoz Investigational Site	Praha 5
France	Sandoz Investigational Site	Marseille	Bouches-Du-Rhone
France	Sandoz Investigational Site	Paris
France	Sandoz Investigational Site	Saint Cyr sur Loire	Indre Et Loire
Germany	Sandoz Investigational Site	Duesseldorf
Germany	Sandoz Investigational Site	Frankfurt Am Main
Germany	Sandoz Investigational Site	Freiburg
Germany	Sandoz Investigational Site	Hannover
Germany	Sandoz Investigational Site	Leipzig
Germany	Sandoz Investigational Site	Mainz
Germany	Sandoz Investigational Site	Marburg
Hungary	Sandoz Investigational Site	Budapest	HUN
Hungary	Sandoz Investigational Site	Budapest	Pest Megye
Hungary	Sandoz Investigational Site	Budapest
Hungary	Sandoz Investigational Site	Budapest
Hungary	Sandoz Investigational Site	Debrecen
Hungary	Sandoz Investigational Site	Sopron
Hungary	Sandoz Investigational Site	Szeged
Hungary	Sandoz Investigational Site	Szekesfehervar
Israel	Sandoz Investigational Site	Haifa
Israel	Sandoz Investigational Site	Jerusalem
Israel	Sandoz Investigational Site	Kfar Saba
Israel	Sandoz Investigational Site	Lod
Israel	Sandoz Investigational Site	Petach Tikva
Israel	Sandoz Investigational Site	Rehovot
Israel	Sandoz Investigational Site	Tel Aviv
Japan	Sandoz Investigational Site	Amagasaki city	Hyogo
Japan	Sandoz Investigational Site	Fukuoka city	Fukuoka
Japan	Sandoz Investigational Site	Hamamatsu-city	Shizuoka
Japan	Sandoz Investigational Site	Inashiki-gun	Ibaraki
Japan	Sandoz Investigational Site	Kagoshima city	Kagoshima
Japan	Sandoz Investigational Site	Kobe-shi	Hyogo
Japan	Sandoz Investigational Site	Kure	Hiroshima
Japan	Sandoz Investigational Site	Meguro-ku	Tokyo
Japan	Sandoz Investigational Site	Nagakute-city	Aichi
Japan	Sandoz Investigational Site	Nagoya	Aichi
Japan	Sandoz Investigational Site	Nagoya	Aichi
Japan	Sandoz Investigational Site	Taito-ku	Tokyo
Japan	Sandoz Investigational Site	Ube	Yamaguchi
Latvia	Sandoz Investigational Site	Riga
Latvia	Sandoz Investigational Site	Riga
Lithuania	Sandoz Investigational Site	Kaunas	Kauno Apskritis
Lithuania	Sandoz Investigational Site	Vilnius
Poland	Sandoz Investigational Site	Bydgoszcz
Poland	Sandoz Investigational Site	Krakow	Malopolska
Poland	Sandoz Investigational Site	Lodz
Poland	Sandoz Investigational Site	Lublin
Poland	Sandoz Investigational Site	Wroclaw
Portugal	Sandoz Investigational Site	Coimbra
Portugal	Sandoz Investigational Site	Coimbra
Portugal	Sandoz Investigational Site	Porto
Slovakia	Sandoz Investigational Site	Bratislava
Slovakia	Sandoz Investigational Site	Bratislava
Slovakia	Sandoz Investigational Site	Trencin
Slovakia	Sandoz Investigational Site	Zilina	Slovak Republic
Spain	Sandoz Investigational Site	Barcelona
Spain	Sandoz Investigational Site	Barcelona
Spain	Sandoz Investigational Site	Bilbao	Pais Vasco
Spain	Sandoz Investigational Site	Oviedo	Asturias
Spain	Sandoz Investigational Site	Pamplona	Navarra
Spain	Sandoz Investigational Site	Sant Cugat	Catalunya
Spain	Sandoz Investigational Site	Zaragoza
United States	Sandoz Investigational Site	Abilene	Texas
United States	Sandoz Investigational Site	Albuquerque	New Mexico
United States	Sandoz Investigational Site	Arcadia	California
United States	Sandoz Investigational Site	Arlington	Texas
United States	Sandoz Investigational Site	Campbell	California
United States	Sandoz Investigational Site	Encino	California
United States	Sandoz Investigational Site	Eugene	Oregon
United States	Sandoz Investigational Site	Fort Myers	Florida
United States	Sandoz Investigational Site	Fullerton	California
United States	Sandoz Investigational Site	Glendale	California
United States	Sandoz Investigational Site	Great Neck	New York
United States	Sandoz Investigational Site	Hagerstown	Maryland
United States	Sandoz Investigational Site	Huntington Beach	California
United States	Sandoz Investigational Site	Liverpool	New York
United States	Sandoz Investigational Site	Lynchburg	Virginia
United States	Sandoz Investigational Site	Marietta	Georgia
United States	Sandoz Investigational Site	Oak Forest	Illinois
United States	Sandoz Investigational Site	Pasadena	California
United States	Sandoz Investigational Site	Phoenix	Arizona
United States	Sandoz Investigational Site	Pinellas Park	Florida
United States	Sandoz Investigational Site	Plantation	Florida
United States	Sandoz Investigational Site	Poway	California
United States	Sandoz Investigational Site	Rapid City	South Dakota
United States	Sandoz Investigational Site	Redlands	California
United States	Sandoz Investigational Site	Rochester	New York
United States	Sandoz Investigational Site	Sacramento	California
United States	Sandoz Investigational Site	Stuart	Florida
United States	Sandoz Investigational Site	Willow Park	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Sandoz

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Bulgaria,  Czechia,  France,  Germany,  Hungary,  Israel,  Japan,  Latvia,  Lithuania,  Poland,  Portugal,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Analysis Systemic VEGF Concentrations in Patients Treated With Aflibercept	Mean VEGF concentrations	Assessment at Week 48 (pre-dose) and Week 52
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)