E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment Naïve Neovascular Age-Related Macular Degeneration (nAMD) and Treatment Naïve diabetic macular edema (DME) |
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E.1.1.1 | Medical condition in easily understood language |
nAMD is an eye disease particularly affects the center of sharp vision (e.g affects reading or driving). DME is a complication of diabetes and causes problem in vision (e.g blurred or wavy vision). |
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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 | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10015919 |
E.1.2 | Term | Eye disorders |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 explore aqueous humor (AH) biomarkers and multimodal imaging features at baseline and over time with and without relation to treatment response • To explore association of genetic polymorphisms with AH biomarkers, multimodal imaging features, and treatment response • To explore whether the biomarkers identified in AH related to treatment response show a similar relationship to treatment response when measured in blood • To describe the relationship between biomarkers of interest in AH and blood at all timepoints tested • To explore the relationship between biomarkers and relevant biochemical pathways in AH at all timepoints tested • To evaluate machine-learning models trained on historic study data for prediction of treatment response |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria for All Participants • Investigator deems collection of > 90 micro liter AH is feasible and safe and participant consents to AH collection • Participants who are treatment-naïve in the study eye (e.g., have not received previous treatment with any anti-VEGF IVT, or any corticosteroids periocular or IVT, or any fluocinolone acetonide IVT implant [i.e. Iluvien or Retisert], or laser or verteporfin photodynamic therapy and no such treatment planned for the time between screening and Day 1). • Decreased BCVA is attributable primarily to nAMD or DME, respectively; with an Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) letter score of 75 to 20 letters • Clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm diagnosis and for follow-up • Only one eye can be the study eye; if both eyes are eligible, the eye with the lower BCVA at Day 1 becomes the study eye. If both eyes have the same BCVA, the right eye will be defined as the study eye • Female Participants; A female is eligible to participate if she is not pregnant (see Appendix 4 of the protocol), not breastfeeding, and at least one of the following conditions applies: o Women of non-childbearing potential (WONCBP), as defined in Appendix 4 of the protocol AND/OR o Women of childbearing potential (WOCBP), who: - Agree to remain abstinent (refrain from heterosexual intercourse) or have to use effective contraception during treatment and for at least 3 months after the last IVT injection of aflibercept. - Have a negative pregnancy test (urine) at Day 1. Inclusion Criteria for nAMD Population • Age>= 50 years Ocular Inclusion Criteria for Study Eye with nAMD • Participants diagnosed with nAMD within the last 12 months. • Participants with subfoveal or juxtafoveal CNV lesion of all types • Study eye is eligible to be treated with aflibercept and treatment can be scheduled according to the prescribing information for nAMD as per label Inclusion Criteria for DME Population • Age >= 18 years • Diagnosis of DM (type 1 or type 2), as defined by the World Health Organization and/or American Diabetes Association Ocular Inclusion Criteria for Study Eye with DME • Participants diagnosed with DME within the last 12 months • DME defined as thickening on spectral domain optical coherence tomography (SD-OCT) involving the center of the macula: CST of ≥ 325 µm with Spectralis® (Heidelberg Engineering, Heidelberg, Germany) • Study eye is eligible to be treated with aflibercept, and treatment can be scheduled according to the prescribing information for DME as per label in the study eye |
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E.4 | Principal exclusion criteria |
Exclusion Criteria for All Participants • Any known hypersensitivity to any contrast media, aflibercept, dilating eye drops, or any of the anesthetics and antimicrobial drops used • Pregnant or breastfeeding women, or women intending to become pregnant during the study and during 3 months after the study • Uncontrolled blood pressure is defined as systolic > 180 mm Hg and/or diastolic > 100 mm Hg • Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within six months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis at any time during the study • History of or currently active other diseases, other non-diabetic metabolic dysfunction, including viral and/or bacterial infections that might affect interpretation of the results of the study, or does not allow the participant to follow the visit schedule, or renders the participant at high risk for aflibercept treatment complications in the opinion of the Investigator. Note: Participants who tested positively for COVID-19/SARS-CoV-2 at any time prior to Day 1 are excluded, regardless of their vaccination status and regardless of presence of COVID-19 symptoms • Active cancer within the past 12 months prior to Day 1 • Any major illness or major surgical procedure one month prior to Day 1 • Stroke or myocardial infarction within 12 months prior to Day 1 • Participant has received blood transfusion within three months prior to screening • Any febrile illness within one week prior to Day 1 • Participants who are currently enrolled in or have participated in any other clinical study involving an investigational product or device, or in any other type of medical research, within three months or 5 half-lives (whichever is longer) prior to Day 1 and up to completion of the study • Any illness that causes immunosuppression or any treatment that leads to immunosuppression within 5 half-lives prior to the Day 1 • Use of any systemic corticosteroids within one month prior to Day 1 • Substance abuse within 12 months prior to screening, in the Investigator's judgment • Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives (whichever is longer) prior to Day 1 • Use of systemic medications known to be toxic to the lens, retina, or optic nerve used during the six-month period or 5 half-lives (whichever is longer) prior to Day 1 or likely need to be used. • Any intraocular surgery in the study eye within three months prior to Day 1 or any planned surgery during the study • Aphakia or implantation of intraocular lens outside of the capsular bag in the study eye • Treatment for dry eye disease (except eye Lubricants) in the study eye within 1 month prior to Day 1 • Any active ocular or periocular infections • Any presence of active intraocular inflammation or any history of intraocular inflammation, idiopathic, infectious, or noninfectious uveitis • History of vitreoretinal surgery/pars plana vitrectomy, corneal transplant, or radiotherapy • Any current ocular condition in the study eye for which, in the opinion of the Investigator, VA loss would not improve from resolution of macular edema • Uncontrolled glaucoma in the study eye • History of glaucoma surgery in the study eye • Any treatment of the study eye with anti-inflammatory eye drops within 1 month prior to Day 1 • Previous treatment with Iluvien or Retisert in fellow eye (non-study eye) • If participants have been treated with any periocular or IVT corticosteroids in the fellow eye, the following washout periods prior to Day 1 apply: o Triamcinolone: 6 months o Ozurdex (dexamethasone IVT implant): 6 months • Participants are currently receiving treatment with Beavu or Avastin in the fellow eye and are unwilling to switch to a protocol-allowed fellow eye treatment during the study • Any current or history of ocular or intraocular condition that may confound assessment of the macula or affect central vision or could either: o Require medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition; or Preclude any visual improvement due to substantial structural damage Exclusion Criteria for nAMD Population Ocular Exclusion Criteria for Study Eye with nAMD • CNV due to causes other than AMD • Retinal pigment epithelial tear involving the macula • Central serous chorioretinopathy • Spherical equivalent of the refractive error demonstrating more than eight diopters of myopia Exclusion Criteria for DME Population • Currently untreated DM or previously untreated participants who initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1 • Hemoglobin A1c (HbA1c) >10%. One rescreening for this criterion is permitted after 8 weeks if the HbA1c value at screening is >10% and <11% Ocular Exclusion Criteria for Study Eye with DME • Any history of or active proliferative DR (PDR) • History of or ongoing rubeosis iridis |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Values of multimodal imaging features at all timepoints tested 2. BCVA score at all timepoints tested 3. Values of AH biomarkers at all timepoints tested 4. Genotypes 5. Values of selected blood biomarkers at all timepoints tested 6. Values of AH biomarkers of interest at all timepoints tested 7. Values of blood biomarkers of interest at all timepoints tested 8. Pathway analysis based on values of AH biomarkers at all timepoints tested 9. Model performance for predicting treatment response based on clinical, imaging and biomarker baseline values |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. At baseline/ Day 1, at Week 8 and at Week 24 (for nAMD), and baseline, at Week 16 and at Week 24 (for DME) 3. At baseline/ Day 1, at Week 8 and at Week 24 (for nAMD), and baseline, at Week 16 and at Week 24 (for DME) 4. At Baseline/ Day 1 or at other scheduled visit 5-7. At baseline/ Day1, at Week 8 and at Week 24 (for nAMD), and baseline, at Week 16 and at Week 24 (for DME) 8-9. From baseline/ Day 1 to Week 24 |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 |
to explore the composition of aqueous humor and features of multimodal retinal imaging |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 2 |
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 |
Colombia |
Korea, Republic of |
Russian Federation |
United States |
Italy |
Poland |
Czechia |
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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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A participant is considered to have completed the study if he/she has completed the last scheduled procedure shown in the Schedules of Activities (SoAs, Section 1.3). The last activity includes a safety follow-up call 5 to 7 days after the final AH sampling and IVT aflibercept administration. The end of the study is defined as the date of the last visit of the last participant (LVLP) occurs. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |