Comparative Study to Evaluate the Efficacy and Safety of MYL-1701P and Eylea® in Subjects With Diabetic Macular Edema (DME) (DME)

A Multi Center, Randomized, Double-Masked, Active-Controlled, Comparative Clinical Study to Evaluate the Efficacy and Safety of MYL-1701P and Eylea® in Subjects With Diabetic Macular Edema (DME)

Three hundred and twenty-four (324) eligible adult subjects with diabetes mellitus with central DME involvement to be randomized 1:1 to intravitreal treatment with MYL-1701P or Eylea®.

The primary endpoint is mean change from baseline in Best Corrected Visual Acuity (BCVA) as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Pharmacokinetics (PK) and immunogenicity to be evaluated in the subjects participating in the study.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: MYL-1701P; Drug: Eylea

Detailed Description

Three hundred and twenty-four (324) eligible adult subjects with diabetes mellitus with central DME involvement to be randomized 1:1 to intravitreal treatment with MYL-1701P or Eylea®. Subjects to receive the assigned treatment until Week 48.

All subjects to return to clinic every 4 weeks to assess safety, efficacy and to guide treatment. Additional visits allowed during the study as specified in the study schedule for safety and pharmacokinetic evaluation.

Pharmacokinetics (PK) and Immunogenicity to be assessed in the subjects participating in the study.

• Study Type: Interventional
• Enrollment (Actual): 355
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Hradec Králové, Czechia, 50005
    • Mylan Investigator Site
  • Olomouc, Czechia, 77900
    • Mylan Investigator Site
  • Pardubice, Czechia, 53002
    • Mylan Investigator Site
  • Praha 2, Czechia, 12808
    • Mylan Investigator Site
  • Praha 5, Czechia, 15000
    • Mylan Investigator Site
  • Zlín, Czechia, 76275
    • Mylan Investigator Site
  • Vinohrady
    • Praha 10, Vinohrady, Czechia, 10034
      • Mylan Investigator Site
• Germany
  • Marburg, Germany, 35043
    • Mylan Investigator Site
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany, 37075
      • Mylan Investigator Site
  • Rheinland-Pflaz
    • Mainz, Rheinland-Pflaz, Germany, 55131
      • Mylan Investigator Site
• Hungary
  • Budapest, Hungary, 1076
    • Mylan Investigator Site
  • Budapest, Hungary, 1106
    • Mylan Investigator Site
  • Debrecen, Hungary, 4032
    • Mylan Investigator Site
  • Nyíregyháza, Hungary, 4400
    • Mylan Investigator Site
  • Pecs, Hungary, 7621
    • Mylan Investigator Site
  • Szeged, Hungary, 6720
    • Mylan Investigator Site
  • Zalaegerszeg, Hungary, 8900
    • Mylan Investigator Site
• India
  • Andhra Pradesh
    • Visakhapatnam, Andhra Pradesh, India, 530040
      • Mylan Investigator Site
  • Delhi
    • New Delhi, Delhi, India, 110029
      • Mylan Investigator Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380015
      • Mylan Investigator Site
    • Ahmedabad, Gujarat, India, 380016
      • Mylan Investigator Site
  • Karnataka
    • Bangalore, Karnataka, India, 560010
      • Mylan Investigator Site
    • Bangalore, Karnataka, India, 560037
      • Mylan Investigator Site
    • Bangalore, Karnataka, India, 560094
      • Mylan Investigator Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400050
      • Mylan Investigator Site
  • Orissa
    • Bhubaneswar, Orissa, India, 751024
      • Mylan Investigator Site
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Mylan Investigator Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302015
      • Mylan Investigator Site
  • Tamilnadu
    • Madurai, Tamilnadu, India, 625020
      • Mylan Investigator Site
    • Tirunelveli, Tamilnadu, India, 627002
      • Mylan Investigator Site
  • Telangana
    • Hyderabad, Telangana, India, 500034
      • Mylan Investigator Site
  • Uttar Pradesh
    • Noida, Uttar Pradesh, India, 201301
      • Mylan Investigator Site
• Japan
  • Fukuoka, Japan, 8110213
    • Mylan Investigator Site
  • Fukushima, Japan, 9601295
    • Mylan Investigator Site
  • Kagoshima, Japan, 8920824
    • Mylan Investigator Site
  • Kumamoto, Japan, 8600027
    • Mylan Investigator Site
  • Nagasaki, Japan, 8528501
    • Mylan Investigator Site
  • Osaka, Japan, 5400006
    • National Hospital Organization Osaka National Hospital
  • Saitama, Japan, 3308553
    • Mylan Investigator Site
  • Aichi
    • Nagoya, Aichi, Japan, 4578510
      • Mylan Investigator Site
  • Fukushima
    • Koriyama, Fukushima, Japan, 9638052
      • Mylan Investigator Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 0608604
      • Mylan Investigator Site
  • Ibaraki
    • Mito, Ibaraki, Japan, 3100845
      • Mylan Investigator Site
  • Kanagawa
    • Yamato, Kanagawa, Japan, 2420001
      • Mylan Investigator Site
  • Shizuoka
    • Susono, Shizuoka, Japan, 4101102
      • Mylan Investigator Site
  • Yamanashi
    • Kōfu, Yamanashi, Japan, 4008506
      • Mylan Investigator Site
• Latvia
  • Jelgava, Latvia, LV-3001
    • Mylan Investigator Site
  • Riga, Latvia, LV-1002
    • Mylan Investigator Site
  • Riga, Latvia, LV-1006
    • Mylan Investigator Site
• Poland
  • Rzeszów, Poland, 35017
    • Mylan Investigator Site
  • Wałbrzych, Poland, 58309
    • Mylan Investigator Site
  • Lodzkie
    • Łódź, Lodzkie, Poland, 91134
      • Mylan Investigator Site
  • Slaskie
    • Katowice, Slaskie, Poland, 40594
      • Mylan Investigator Site
  • Tarnow
    • Tarnów, Tarnow, Poland, 33100
      • Mylan Investigator Site
  • Warminsko-Mazurskie
    • Olsztyn, Warminsko-Mazurskie, Poland, 10424
      • Mylan Investigator Site
• Russian Federation
  • Moscow, Russian Federation, 119021
    • Mylan Investigator Site
  • Novosibirsk, Russian Federation, 630096
    • Mylan Investigator Site
  • Omsk, Russian Federation, 644042
    • Mylan Investigator Site
  • Saint Petersburg, Russian Federation, 197022
    • Mylan Investigator Site
  • Tatarstan Resp.
    • Kazan, Tatarstan Resp., Russian Federation, 420012
      • Mylan Investigator Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Mylan Investigator Site
    • Phoenix, Arizona, United States, 85020
      • Mylan Investigator Site
  • California
    • Sacramento, California, United States, 95841
      • Mylan Investigator Site
  • Florida
    • Saint Petersburg, Florida, United States, 33711
      • Mylan Investigator Site
    • Winter Haven, Florida, United States, 33880
      • Mylan Investigator Site
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Mylan Investigator Site
  • Kansas
    • Shawnee Mission, Kansas, United States, 66204
      • Mylan Investigator Site
  • Kentucky
    • Paducah, Kentucky, United States, 42001
      • Mylan Investigator Site
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Mylan Investigator Site
  • South Carolina
    • Ladson, South Carolina, United States, 29456
      • Mylan Investigator Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Mylan Investigator Site
  • Texas
    • Abilene, Texas, United States, 79606
      • Mylan Investigator Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Mylan Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects age ≥ 18 years.
2. Subjects have type 1 or type 2 diabetes mellitus who present with central DME involvement in the study eye.
3. The cause of decreased vision in the study eye has been attributed primarily to DME by the Investigator.
4. Subject is able to understand and voluntarily provide written informed consent to participate in the study.
5. If female of child bearing potential, the subject must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at baseline visit, and should not be nursing or planning a pregnancy.

6. If female, subject must be:

   1. Surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or
   2. Of childbearing potential and practicing an acceptable form of birth control (defined as the use of an intrauterine device; a barrier method, like condom, with spermicide; any form of hormonal contraceptives; or abstinence from sexual intercourse) starting 60 days prior to dosing and continuing at least 90 days following the last treatment.
   3. Of non-childbearing potential (i.e., postmenopausal for at least 1 year).
7. If male, subject must be surgically or biologically sterile. If not sterile, the subject must agree to use an acceptable form of birth control with sexual partner (as described in inclusion criteria #6b of protocol) or abstain from sexual relations during the study period and up to 90 days following the last treatment dose.
8. Subject is willing to comply with the study duration, study visits and study related procedures.

Exclusion Criteria:

1. Subjects with known hypersensitivity to aflibercept or any of the excipients
2. Subjects with current or planned use of systemic medications known to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol
3. Subjects with uncontrolled hypertension defined as systolic blood pressure >160mm Hg or diastolic blood pressure > 95 mm of Hg.
4. Subjects with a history of cerebrovascular accident or myocardial infarction within 6 months of randomization.
5. Subjects with history of use of intraocular corticosteroids anytime in the past or periocular (subconjunctival, intra-scleral, sub-tenon or retrobulbar) corticosteroids within 4 months of randomization
6. Subjects who have only one functional eye, even if the eye met all other study requirements, or who have an ocular condition on the fellow eye with a poorer prognosis than the study eye.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MYL-1701P	Drug: MYL-1701P; Subjects will receive intravitreal injections of MYL-1701P throughout the 52-week treatment period, with the last dose at 48 weeks. The additional doses may be administered in accordance with the protocol.
Active Comparator: Eylea	Drug: Eylea; Subjects will receive intravitreal injections of Eylea throughout the 52-week treatment period, with the last dose at 48 weeks. The additional doses may be administered in accordance with the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8	Mean change from baseline in BCVA as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8. Best Corrected Visual Acuity (BCVA) is measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the ETDRS chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.	Baseline and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Mean Change From Baseline in Central Retinal Thickness (CRT)	The mean change from baseline in Central Retinal Thickness as determined by Spectral domain- Optical coherence tomography (SD-OCT) over time	From baseline to week 52
The Mean Change in BCVA	Mean change from baseline in BCVA as assessed by ETDRS letters over time. Best Corrected Visual Acuity (BCVA) is measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the ETDRS chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening	From baseline to week 52
Number of Subjects Who Gained ≥15 Letters From Baseline in BCVA	Number of subjects who gained ≥15 letters from baseline in BCVA, assessed in change from baseline in ETDRS letters over time	From baseline to week 52
Number of Administrations of Study Drug Required	The mean number of doses administered during the 52 weeks of study	From baseline to week 52
Number of Participants With Treatment Emergent Adverse Events	Number of Participants with Treatment Emergent Adverse Events (Safety and tolerability)	From baseline to week 52
Number of Subjects With Induced and Boosted Anti-Drug Antibodies	Number of subjects with induced and boosted Anti-Drug Antibodies (ADA) (Immunogenicity)	From baseline to week 52
Concentration of Aflibercept in Blood (Pharmacokinetics)	Free Drug Concentration of aflibercept in blood (Pharmacokinetics)	2 Days after Week 16 Injection

Collaborators and Investigators

• Sponsor: Mylan Pharmaceuticals Inc
• Collaborators: Momenta Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2018
• Primary Completion (Actual): November 10, 2020
• Study Completion (Actual): September 10, 2021

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Diabetic Macular Edema,; BCVA,; ETDRS Letters.
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema
• Other Study ID Numbers: MYL-1701P-3001

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