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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: MYL-1701P
* Drug: Eylea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects age ≥ 18 years. Subjects have type 1 or type 2 diabetes mellitus who present with central DME involvement in the study eye. The cause of decreased vision in the study eye has been attributed primarily to DME by the Investigator. Subject is able to understand and voluntarily provide written informed consent to participate in the study. 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. If female, subject must be: Surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or 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. Of non-childbearing potential (i.e., postmenopausal for at least 1 year). 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. Subject is willing to comply with the study duration, study visits and study related procedures. Exclusion Criteria: Subjects with known hypersensitivity to aflibercept or any of the excipients 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 Subjects with uncontrolled hypertension defined as systolic blood pressure >160mm Hg or diastolic blood pressure > 95 mm of Hg. Subjects with a history of cerebrovascular accident or myocardial infarction within 6 months of randomization. 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are assigned to either MYL-1701P or Eylea groups in parallel for the duration of the study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MYL-1701P<br>MYL-1701P | Drug: MYL-1701P<br>* 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.<br>|
| Active Comparator: Eylea<br>Eylea | Drug: Eylea<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCVA,, Diabetic Macular Edema,, ETDRS Letters.