E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Damage to the retina and swelling of macula as a complication of diabetes |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057934 |
E.1.2 | Term | Diabetic macular edema |
E.1.2 | System Organ Class | 100000004853 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the clinical equivalence of MYL-1701P and Eylea over 8 weeks of treatment at doses and regimen recommended by the Prescribing Information for Eylea, as assessed by change from baseline to week 8 in best corrected visual acuity (BCVA). |
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E.2.2 | Secondary objectives of the trial |
• To compare the efficacy of MYL-1701P and Eylea as measured by change in CRT over time • To compare the efficacy of MYL-1701P and Eylea as measured by change in BCVA over time • To compare safety, tolerability, pharmacokinetics, and immunogenicity over time of MYL-1701P and Eylea • To compare the number of administrations of study drug required over the treatment period • To compare impact of immunogenicity on efficacy and safety |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PK Substudy: A subset of patients will participate in a substudy to evaluate pharmacokinetics of MYL-1701P and Eylea |
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E.3 | Principal 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: a. Surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or b. 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. c. 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. |
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E.4 | Principal 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 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the mean change from baseline in BCVA as assessed by ETDRS letters at week 8. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The mean change from baseline in CRT as determined by spectral-domain-optical coherence tomography (SD-OCT) over time • The mean change in BCVA over time • Proportion 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints as detailed in the Schedule of Activities in the protocol |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
Germany |
Hungary |
Japan |
Latvia |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is considered to be the date of last subject last visit or the date of early termination of the study whichever is the later. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial days | 24 |