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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03610646

Acronym

DME

Enrollment

355

Registered

2018-08-01

Start date

2018-08-23

Completion date

2021-09-10

Last updated

2023-03-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetic Macular Edema

Keywords

Diabetic Macular Edema,, BCVA,, ETDRS Letters.

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.

Interventions

DRUGMYL-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.

DRUGEylea

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Masking description

Masked study drug kits will be supplied to sites as necessary during the study. The outside label of the box will not reveal the identity of the product inside (whether it is Eylea or MYL-1701P) and will be assigned in a masked fashion through the Interactive Response Technology (IRT) system. An un-masked team will identified at site, to be responsible for preparation and administration of the study drug.

Intervention model description

Participants are assigned to either MYL-1701P or Eylea groups in parallel for the duration of the study

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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
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)
Concentration of Aflibercept in Blood (Pharmacokinetics)	2 Days after Week 16 Injection	Free Drug Concentration of aflibercept in blood (Pharmacokinetics)
Number of Participants With Treatment Emergent Adverse Events	From baseline to week 52	Number of Participants with Treatment Emergent Adverse Events (Safety and tolerability)

Countries

Czechia, Germany, Hungary, India, Japan, Latvia, Poland, Russia, United States

Participant flow

Participants by arm

Arm	Count
MYL-1701P MYL-1701P MYL-1701P: Subjects received intravitreal injections of MYL-1701P throughout the 52-week treatment period, with the last dose at 48 weeks. Additional doses were administered in accordance with the protocol.	179
Eylea Eylea Eylea: Subjects received intravitreal injections of Eylea throughout the 52-week treatment period, with the last dose at 48 weeks. Additional doses were administered in accordance with the protocol.	176
Total	355

Baseline characteristics

Characteristic	Eylea	MYL-1701P	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	70 Participants	78 Participants	148 Participants
Age, Categorical Between 18 and 65 years	106 Participants	101 Participants	207 Participants
Age, Continuous	61.6 Years STANDARD_DEVIATION 9.93	62.8 Years STANDARD_DEVIATION 8.37	62.2 Years STANDARD_DEVIATION 9.18
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	58 Participants	62 Participants	120 Participants
Race (NIH/OMB) Black or African American	3 Participants	2 Participants	5 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) White	114 Participants	114 Participants	228 Participants
Region of Enrollment Czechia	23 Participants	20 Participants	43 Participants
Region of Enrollment Germany	8 Participants	3 Participants	11 Participants
Region of Enrollment Hungary	27 Participants	25 Participants	52 Participants
Region of Enrollment India	39 Participants	38 Participants	77 Participants
Region of Enrollment Japan	19 Participants	22 Participants	41 Participants
Region of Enrollment Latvia	9 Participants	9 Participants	18 Participants
Region of Enrollment Poland	15 Participants	22 Participants	37 Participants
Region of Enrollment Russia	5 Participants	8 Participants	13 Participants
Region of Enrollment United States	31 Participants	32 Participants	63 Participants
Sex: Female, Male Female	67 Participants	72 Participants	139 Participants
Sex: Female, Male Male	109 Participants	107 Participants	216 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 178	4 / 176
other Total, other adverse events	53 / 178	61 / 176
serious Total, serious adverse events	31 / 178	23 / 176

Outcome results

Primary

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.

Time frame: Baseline and 8 weeks

Population: The intention-to-treat (ITT) analysis set consists of all randomized subjects.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
MYL-1701P	Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8	6.60 BCVA letter score	Standard Error 0.548
Eylea	Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8	6.56 BCVA letter score	Standard Error 0.548

90% CI: [-1.16, 1.24]

Secondary

Concentration of Aflibercept in Blood (Pharmacokinetics)

Free Drug Concentration of aflibercept in blood (Pharmacokinetics)

Time frame: 2 Days after Week 16 Injection

Population: All subjects who have signed the Informed Consent Form (ICF) for participation in Pharmacokinetics (PK) subpopulation and have at least one measured concentration of study treatment.

Arm	Measure	Value (MEAN)	Dispersion
MYL-1701P	Concentration of Aflibercept in Blood (Pharmacokinetics)	34.355 ng/ml	Standard Deviation 30.693
Eylea	Concentration of Aflibercept in Blood (Pharmacokinetics)	30.758 ng/ml	Standard Deviation 32.3208

Secondary