Clinical trial NCT04864834: Phase III Study Assessing the Efficacy, Safety and Immunogenicity of SOK583A1 Versus Eylea® in Patients With Neovascular Age-related Macular Degeneration
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neovascular Age-related Macular Degeneration
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
First posted: 2021-04-29
Enrollment: 485
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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?

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

Eligibility criteria: 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).

Primary outcomes:
measure: 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.
timeFrame: Change from baseline in mean BCVA score at Week 8
Secondary outcomes:
measure: Similarity in the Anatomical Outcome Between SOK583A1 and Eylea EU
timeFrame: Week 1, 4, 8, 24 and 52
measure: Similarity in the Anatomical Outcome Between SOK583A1 and Eylea EU
timeFrame: Week 8 and 52
measure: Similarity of Efficacy Between SOK583A1 and Eylea EU in Terms of BCVA
timeFrame: Week 24 and 52
measure: Similarity Between SOK583A1 and Eylea EU in Terms of Safety
timeFrame: 52 weeks
measure: Similarity Between SOK583A1 and Eylea EU in Terms of Immunogenicity
timeFrame: Week 52
measure: Systemic Exposure to SOK583A1 and Eylea EU in Participants of the Pharmacokinetic (PK) Assessment
timeFrame: Baseline (pre-dose) and 24 hours after the first injection (day 2) and third injection (day 58)
Other outcomes:
measure: Analysis Systemic VEGF Concentrations in Patients Treated With Aflibercept
timeFrame: Assessment at Week 48 (pre-dose) and Week 52
Locations:
city: Phoenix
country: United States
facility: Sandoz Investigational Site
state: Arizona
city: Arcadia
country: United States
facility: Sandoz Investigational Site
state: California
city: Campbell
country: United States
facility: Sandoz Investigational Site
state: California
city: Encino
country: United States
facility: Sandoz Investigational Site
state: California
city: Fullerton
country: United States
facility: Sandoz Investigational Site
state: California
city: Glendale
country: United States
facility: Sandoz Investigational Site
state: California
city: Huntington Beach
country: United States
facility: Sandoz Investigational Site
state: California
city: Pasadena
country: United States
facility: Sandoz Investigational Site
state: California
city: Poway
country: United States
facility: Sandoz Investigational Site
state: California
city: Redlands
country: United States
facility: Sandoz Investigational Site
state: California
city: Sacramento
country: United States
facility: Sandoz Investigational Site
state: California
city: Fort Myers
country: United States
facility: Sandoz Investigational Site
state: Florida
city: Pinellas Park
country: United States
facility: Sandoz Investigational Site
state: Florida
city: Plantation
country: United States
facility: Sandoz Investigational Site
state: Florida
city: Stuart
country: United States
facility: Sandoz Investigational Site
state: Florida
city: Marietta
country: United States
facility: Sandoz Investigational Site
state: Georgia
city: Oak Forest
country: United States
facility: Sandoz Investigational Site
state: Illinois
city: Hagerstown
country: United States
facility: Sandoz Investigational Site
state: Maryland
city: Albuquerque
country: United States
facility: Sandoz Investigational Site
state: New Mexico
city: Great Neck
country: United States
facility: Sandoz Investigational Site
state: New York
city: Liverpool
country: United States
facility: Sandoz Investigational Site
state: New York
city: Rochester
country: United States
facility: Sandoz Investigational Site
state: New York
city: Eugene
country: United States
facility: Sandoz Investigational Site
state: Oregon
city: Rapid City
country: United States
facility: Sandoz Investigational Site
state: South Dakota
city: Abilene
country: United States
facility: Sandoz Investigational Site
state: Texas
city: Arlington
country: United States
facility: Sandoz Investigational Site
state: Texas
city: Willow Park
country: United States
facility: Sandoz Investigational Site
state: Texas
city: Lynchburg
country: United States
facility: Sandoz Investigational Site
state: Virginia
city: Albury
country: Australia
facility: Sandoz Investigational Site
state: New South Wales
city: Liverpool
country: Australia
facility: Sandoz Investigational Site
state: New South Wales
city: Parramatta
country: Australia
facility: Sandoz Investigational Site
state: New South Wales
city: Sydney
country: Australia
facility: Sandoz Investigational Site
state: New South Wales
city: Adelaide
country: Australia
facility: Sandoz Investigational Site
state: South Australia
city: Melbourne
country: Australia
facility: Sandoz Investigational Site
state: Victoria
city: Linz
country: Austria
facility: Sandoz Investigational Site
state: Oberoesterreich
city: Linz
country: Austria
facility: Sandoz Investigational Site
state: Upper Austria
city: Graz
country: Austria
facility: Sandoz Investigational Site
city: Sofia
country: Bulgaria
facility: Sandoz Investigational Site
city: Pardubice
country: Czechia
facility: Sandoz Investigational Site
city: Praha 5
country: Czechia
facility: Sandoz Investigational Site
city: Praha
country: Czechia
facility: Sandoz Investigational Site
city: Marseille
country: France
facility: Sandoz Investigational Site
state: Bouches-Du-Rhone
city: Saint Cyr sur Loire
country: France
facility: Sandoz Investigational Site
state: Indre Et Loire
city: Paris
country: France
facility: Sandoz Investigational Site
city: Duesseldorf
country: Germany
facility: Sandoz Investigational Site
city: Frankfurt Am Main
country: Germany
facility: Sandoz Investigational Site
city: Freiburg
country: Germany
facility: Sandoz Investigational Site
city: Hannover
country: Germany
facility: Sandoz Investigational Site
city: Leipzig
country: Germany
facility: Sandoz Investigational Site
city: Mainz
country: Germany
facility: Sandoz Investigational Site
city: Marburg
country: Germany
facility: Sandoz Investigational Site
city: Budapest
country: Hungary
facility: Sandoz Investigational Site
state: HUN
city: Budapest
country: Hungary
facility: Sandoz Investigational Site
state: Pest Megye
city: Budapest
country: Hungary
facility: Sandoz Investigational Site
city: Budapest
country: Hungary
facility: Sandoz Investigational Site
city: Debrecen
country: Hungary
facility: Sandoz Investigational Site
city: Sopron
country: Hungary
facility: Sandoz Investigational Site
city: Szeged
country: Hungary
facility: Sandoz Investigational Site
city: Szekesfehervar
country: Hungary
facility: Sandoz Investigational Site
city: Haifa
country: Israel
facility: Sandoz Investigational Site
city: Jerusalem
country: Israel
facility: Sandoz Investigational Site
city: Kfar Saba
country: Israel
facility: Sandoz Investigational Site
city: Lod
country: Israel
facility: Sandoz Investigational Site
city: Petach Tikva
country: Israel
facility: Sandoz Investigational Site
city: Rehovot
country: Israel
facility: Sandoz Investigational Site
city: Tel Aviv
country: Israel
facility: Sandoz Investigational Site
city: Nagakute-city
country: Japan
facility: Sandoz Investigational Site
state: Aichi
city: Nagoya
country: Japan
facility: Sandoz Investigational Site
state: Aichi
city: Nagoya
country: Japan
facility: Sandoz Investigational Site
state: Aichi
city: Fukuoka city
country: Japan
facility: Sandoz Investigational Site
state: Fukuoka
city: Kure
country: Japan
facility: Sandoz Investigational Site
state: Hiroshima
city: Amagasaki city
country: Japan
facility: Sandoz Investigational Site
state: Hyogo
city: Kobe-shi
country: Japan
facility: Sandoz Investigational Site
state: Hyogo
city: Inashiki-gun
country: Japan
facility: Sandoz Investigational Site
state: Ibaraki
city: Kagoshima city
country: Japan
facility: Sandoz Investigational Site
state: Kagoshima
city: Hamamatsu-city
country: Japan
facility: Sandoz Investigational Site
state: Shizuoka
city: Meguro-ku
country: Japan
facility: Sandoz Investigational Site
state: Tokyo
city: Taito-ku
country: Japan
facility: Sandoz Investigational Site
state: Tokyo
city: Ube
country: Japan
facility: Sandoz Investigational Site
state: Yamaguchi
city: Riga
country: Latvia
facility: Sandoz Investigational Site
city: Riga
country: Latvia
facility: Sandoz Investigational Site
city: Kaunas
country: Lithuania
facility: Sandoz Investigational Site
state: Kauno Apskritis
city: Vilnius
country: Lithuania
facility: Sandoz Investigational Site
city: Krakow
country: Poland
facility: Sandoz Investigational Site
state: Malopolska
city: Bydgoszcz
country: Poland
facility: Sandoz Investigational Site
city: Lodz
country: Poland
facility: Sandoz Investigational Site
city: Lublin
country: Poland
facility: Sandoz Investigational Site
city: Wroclaw
country: Poland
facility: Sandoz Investigational Site
city: Coimbra
country: Portugal
facility: Sandoz Investigational Site
city: Coimbra
country: Portugal
facility: Sandoz Investigational Site
city: Porto
country: Portugal
facility: Sandoz Investigational Site
city: Zilina
country: Slovakia
facility: Sandoz Investigational Site
state: Slovak Republic
city: Bratislava
country: Slovakia
facility: Sandoz Investigational Site
city: Bratislava
country: Slovakia
facility: Sandoz Investigational Site
city: Trencin
country: Slovakia
facility: Sandoz Investigational Site
city: Oviedo
country: Spain
facility: Sandoz Investigational Site
state: Asturias
city: Sant Cugat
country: Spain
facility: Sandoz Investigational Site
state: Catalunya
city: Pamplona
country: Spain
facility: Sandoz Investigational Site
state: Navarra
city: Bilbao
country: Spain
facility: Sandoz Investigational Site
state: Pais Vasco
city: Barcelona
country: Spain
facility: Sandoz Investigational Site
city: Barcelona
country: Spain
facility: Sandoz Investigational Site
city: Zaragoza
country: Spain
facility: Sandoz Investigational Site
Study officials:
References: