E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic Macular Edema (DME) |
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E.1.1.1 | Medical condition in easily understood language |
DME is an accumulation of fluid in the macula, the part of the retina that controls our most detailed vision abilities-due to leaking blood vessels |
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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 investigate the effect of RO7200220 on best corrected visual acuity (BCVA) |
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E.2.2 | Secondary objectives of the trial |
• To assess the safety and tolerability of RO7200220 • To investigate the effect of RO7200220 on additional BCVA outcomes • To investigate the effect of RO7200220 on anatomical outcome measures using spectral domain optical coherence tomography (SD-OCT)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age >= 18 years • Diagnosis of diabetes mellitus (DM; Type 1 or Type 2) • Agrees to use protocol defined methods of contraception • Macular edema associated with diabetic retinopathy (DR) with CST of ≥ 325 µm with Spectralis® • Decreased visual acuity (VA) attributable primarily to DME, with BCVA letter score of 73 to 19 letters on ETDRS-like charts at screening. • Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis
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E.4 | Principal exclusion criteria |
• Any major illness or major surgical procedure within 4 weeks prior to Day 1 • Any febrile illness within 1 week prior to screening or Day 1 • Any stroke or myocardial infarction within 24 weeks prior to Day 1 • Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 24 weeks prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis at any time during the study • Active malignancy within 1 year of screening 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 (PSA) for > 1 year • History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of either of the Investigational Medicinal Products (IMPs) or that might affect interpretation of the results of the study or renders the participant at high risk for treatment complications in the opinion of the Investigator • Any known hypersensitivity to any of the following compounds: fluorescein, biologic IVT agents such as Lucentis® (ranibizumab), Eylea® (aflibercept), Avastin®(bevacizumab),Beovu® (brolucizumab), any ingredient of the formulation used, dilating eye drops, or any anesthetics and antimicrobial drops used • Evidence of HIV infection and/or positive human HIV antibodies; evidence of syphilis or tuberculosis and/or positive assay •Prior or concomitant periocular or IVT corticosteroids in the study eye (Triamcinolone, Ozurdex®: 16 weeks prior Day 1, ILUVIEN® or Retisert®: 3 years prior Day1) • Prior or concomitant treatment with IVT anti-VEGF therapy in thestudy eye within 8 weeks prior to Day 1; Vabysmo® within 16 weeks prior to Day 1, prior Beovu® is not permitted • Any previous or concomitant systemic corticosteroids within 4 weeks prior to Day 1 • Any previous or concomitant systemic anti-VEGF treatment within 24 weeks prior to Day 1 • Any previous or concomitant use of systemic anti-IL-6 or anti-IL-6-receptor treatment • Any concurrent use of biologics for immune-related diseases • Participants who are currently enrolled or have participated in any other clinical study 12 weeks prior Day 1 (brolucizumab (Beovu®): ever;RO7200220: <=24 weeks prior to Day 1) • Uncontrolled blood pressure (BP), defined as systolic >180 mmHG and/or diastolic >100 mmHg. • Participants with HbA1c > 12% at screening • Any proliferative DR • Any panretinal photocoagulation prior to Day 1 • Macular (focal, grid, or micropulse) laser treatment prior to Day 1 • History of vitreoretinal surgery/pars plana vitrectomy, including PDS with ranibizumab implant/explant surgery • Any cataract surgery within 12 weeks prior to Day 1 or any planned surgery during the study • History of any glaucoma surgery • Uncontrolled glaucoma • History of rubeosis iridis • Any concurrent ocular conditions that, in the opinion of the Investigator require medical or surgical intervention during the study, likely contribute to worsening of BCVA or preclude any visual improvement. • Rhegmatogenous or tractional retinal detachment, pre-retinal and/or sub-macular fibrosis, vitreomacular traction, foveal hard exudates, or epiretinal membrane involving the fovea or disrupting the macular architecture, as evaluated by the Central Reading Center (CRC) • Actual or history of myopia > -8 diopters • Any active ocular or periocular infection on Day 1 • Any presence of active intraocular inflammation on Day 1 or any history of intraocular inflammation (noninfectious or infectious uveitis of any type) • Non-functioning non-study eye
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from baseline in BCVA averaged over Week 44 and Week 48 in treatment-naïve participants |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline to Week 44 and Week 48 |
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E.5.2 | Secondary end point(s) |
1. Incidence, severity, and nature of adverse events (ocular and systemic) 2. Incidence of abnormal laboratory findings, abnormal vital signs and electrocardiogram (ECG) parameters 3. Incidence of abnormalities recorded in standard ophthalmological assessments (local safety and tolerability) 4. Change from baseline in BCVA averaged over Week 44 and Week 48 in previously treated participants and the overall enrolled population 5. Change from baseline in BCVA averaged over Week 20 and Week 24 in treatment-naïve participants, previously treated participants and the overall enrolled population 6. Change from baseline in BCVA averaged over Week 32 and Week 36 in treatment-naïve participants previously treated participants and the overall enrolled population 7. Change from baseline in BCVA over time 8. Proportion of participants gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 letters in BCVA from baseline over time 9. Proportion of patients avoiding a loss of ≥ 15, ≥ 10, ≥ 5, or ≥ 0 letters in BCVA from baseline over time 10. Proportion of participants with BCVA ≥ 69 letters (20/40 Snellen equivalent), or ≥ 84 letters (20/20 Snellen equivalent) over time 11. Proportion of participants with BCVA of ≤38 letters (Snellen equivalent 20/200) over time 12. Change from baseline in Central Subfield Thickness (CST) at Week 48 13. Change from baseline in CST at Week 36 14. Change from baseline in CST at Week 24 15. Change from baseline in CST over time 16. Proportion of participants with absence of DME (CST <325 μm for Spectralis SD-OCT, or <315 μm for Cirrus SD-OCT or Topcon SDOCT) over time 17. Proportion of participants with absence of intraretinal fluid and/or subretinal fluid over time |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. Up to Week 72 4. Baseline to Week 44 and Week 48 5. Baseline to Week 20 and Week 24 6. Baseline to Week 32 and Week 36 7-11. Baseline to Week 72 12. Baseline to Week 48 13. Baseline to Week 36 14. Baseline to Week 24 15-17. Baseline to Week 72
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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) | 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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Czechia |
Korea, Republic of |
Poland |
Spain |
United Kingdom |
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 the study is defined as the date when the last participant, last observation (LPLO) 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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |