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

Phase 3

Completed

• Conditions: Diabetic Macular Edema
• Interventions: Drug: MYL-1701P; Drug: Eylea

• Registration Number: NCT03610646
• Lead Sponsor: Mylan Pharmaceuticals Inc

Brief Summary

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

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 Timeline

• Study First Submitted: 2018-07-09
• Study First Submitted QC: 2018-07-25
• Study First Posted: 2018-08-01
• Study Start: 2018-08-23
• Primary Completion: 2020-11-10
• Study Completion: 2021-09-10
• Results First Submitted: 2022-06-10
• Status Verified: 2023-02
• Results First Submitted QC: 2023-02-07
• Last Update Submitted: 2023-02-07
• Results First Posted: 2023-03-07
• Last Update Posted: 2023-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 355

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MYL-1701P	MYL-1701P	MYL-1701P
Eylea	Eylea	Eylea

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8	Baseline and 8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
The Mean Change From Baseline in Central Retinal Thickness (CRT)	From baseline to week 52	The mean change from baseline in Central Retinal Thickness as determined by Spectral domain- Optical coherence tomography (SD-OCT) over time
Concentration of Aflibercept in Blood (Pharmacokinetics)	2 Days after Week 16 Injection	Free Drug Concentration of aflibercept in blood (Pharmacokinetics)
The Mean Change in BCVA	From baseline to week 52	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
Number of Subjects Who Gained ≥15 Letters From Baseline in BCVA	From baseline to week 52	Number of subjects who gained ≥15 letters from baseline in BCVA, assessed in change from baseline in ETDRS letters over time
Number of Administrations of Study Drug Required	From baseline to week 52	The mean number of doses administered during the 52 weeks of study
Number of Participants With Treatment Emergent Adverse Events	From baseline to week 52	Number of Participants with Treatment Emergent Adverse Events (Safety and tolerability)
Number of Subjects With Induced and Boosted Anti-Drug Antibodies	From baseline to week 52	Number of subjects with induced and boosted Anti-Drug Antibodies (ADA) (Immunogenicity)

Trial Locations

Locations (3)

Mylan Investigator site; 🇮🇳 Bangalore, Karnataka, India

Mylan Investigator Site; 🇷🇺 Saint Petersburg, Russian Federation

National Hospital Organization Osaka National Hospital; 🇯🇵 Osaka, Japan