E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic Macular Edema, a complication of Diabetic Retinopathy
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E.1.1.1 | Medical condition in easily understood language |
DME is a complication of diabetes caused by fluid accumulation in the macula that can affect the fovea. |
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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 explore the associations over time between clinical assessments, multimodal imaging assessments, aqueous humor (AH) biomarker patterns, and genetic polymorphisms |
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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 |
• Age 18 years Type of DME Patients and Disease Characteristics • Diagnosis of diabetes mellitus (Type 1 or Type 2), as defined by the World Health Organization (WHO) and/or American Diabetes Association • Hemoglobin A1c (HbA1c) <= 10% • Patients who are IVT treatment-naïve in the study eye Ocular Inclusion Criteria for Study Eye • Diabetic macular edema (DME) defined as macular thickening by spectral-domain optical coherence tomography (SD-OCT) involving the center of the macula: CST of ≥325 μm with Spectralis® at screening. This inclusion criterion is to be assessed by the central reading center (CRC) • Decreased VA attributable primarily to DME, with BCVA letter score of 75 to 20 letters (both inclusive) on ETDRS-like charts at the screening visit • Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis Contraception • For women of childbearing potential: agreement to remain abstinent or use contraception, must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of faricimab
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E.4 | Principal exclusion criteria |
Medical Conditions • Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1 • Any known hypersensitivity to any of the components in the faricimab injection, dilating eye drops, or any of the anesthetics and antimicrobial preparations used by the patient during the study • Any major illness or major surgical procedure within 1 month before the Day 1. One re-screening for this criterion is permitted • History of other diseases, other non-diabetic metabolic dysfunction, physical examination finding, historical or current clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the faricimab or that might affect interpretation of the results of the study or renders the patient at high-risk for treatment complications, in the opinion of the Investigator • Active cancer within the past 12 months prior to Day 1 except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of ≤6 and a stable prostate-specific antigen for >12 months • Stroke or myocardial infarction within 12 months prior to the Day 1. One re-screening for this criterion is permitted • Any febrile illness within 1 week prior to Day 1. One re-screening for this criterion is permitted • Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab • WOCBP must have a negative serum pregnancy test result within 28 days prior to initiation of faricimab and a negative urine pregnancy test at the baseline visit • Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 6 months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis at any time during the study • Any condition resulting in a compromised immune system that is likely to impact the AH inflammatory biomarkers. • Patients 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 3 months or 5 half-lives prior to Day 1 and up to completion of the current study • Substance abuse occurring within 12 months prior to screening, in the Investigator's judgment • Use of systemic immunomodulatory treatments within 6 months or 5 half-lives prior to Day 1, systemic corticosteroids within 1 month prior to Day 1 • Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives prior to Day 1 • Use of systemic medications known to be toxic to the lens, retina or optic nerve used during the 6-month period or 5 half-lives prior to Day 1 or likely need to be used • Received a blood transfusion within 3 months prior to the screening visit, received any treatment that leads to immunosuppression within 6 months or 5 half-lives prior to Day 1 Ocular Exclusion Criteria for Study Eye • High-risk PDR defined as ETDRS DRSS. This exclusion criterion is to be assessed by the CRC • Any history of or ongoing rubeosis iridis • Any panretinal photocoagulation or macular laser photocoagulation treatment received in the study eye prior to the screening visit or expected to be received between the screening visit and Day 1 • Any history of treatment with anti-VEGF or any periocular or IVT corticosteroids in the study eye and no such treatment planned for the time between screening and Day 1 • Any treatment for dry eye disease in the last month prior to Day 1. Lubricating eye drops and ointments are permitted • Any treatment with anti-inflammatory eye drops within 1 month prior to Day 1 • Any intraocular surgery within 3 months prior to Day 1 or any planned surgery during the study, any glaucoma surgery/laser procedure removing the iris, trabecular meshwork, or ciliary body prior to the screening visit. Only iris surgery/laser might be allowed if they occurred more than 6 months prior to Day 1. • History of vitreoretinal surgery/pars plana vitrectomy, corneal transplant, or radiotherapy • Any active or suspected ocular or periocular infections on Day 1 • Any presence of active intraocular inflammation on Day 1 or any history of intraocular inflammation • Any history of idiopathic, infectious, or noninfectious uveitis • Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision • Any current ocular condition or other causes of visual impairment for which, in the opinion of the Investigator, VA loss would not improve from resolution of macular edema Ocular Exclusion Criteria for Fellow Eye • Patient is currently receiving treatment with brolucizumab or bevacizumab in the non-study eye and is unwilling to switch to a protocol allowed non-study eye treatment during the study • Any previous treatment with Iluvien® or Retisert® in the non-study eye • Non-functioning non-study eye
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Change in DRSS between day one and day 112 |
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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) |
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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 |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 18 |
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 |
Argentina |
Canada |
United States |
Poland |
Germany |
Italy |
Croatia |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |