E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Macular edema secondary to Branch Retinal Vein Occlusion |
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E.1.1.1 | Medical condition in easily understood language |
Macular edema is a leading cause of vision impairment in patients with branch retinal vein occlusion. It is caused by fluid accumulation in the macula due to a blockade in blood flow. |
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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 | PT |
E.1.2 | Classification code | 10038907 |
E.1.2 | Term | Retinal vein occlusion |
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 evaluate the efficacy of faricimab 6 mg intravitreal (IVT) injections on best corrected visual acuity (BCVA) outcomes |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of faricimab on additional BCVA outcomes • To evaluate the frequency of faricimab treatment administration • To evaluate the efficacy of faricimab on anatomical outcome measures using optical coherence tomography (OCT) • To evaluate the ocular and systemic safety and tolerability of faricimab • To characterize the systemic pharmacokinetics of faricimab • To evaluate the antibody immune response to faricimab
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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 |
EXPLORATORY SUBSTUDY At selected sites, the Sponsor may propose exploratory substudies associated with the Study GR41984 protocol. Each substudy will be documented in a separate substudy protocol and will have a separate associated Informed Consent Form. |
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E.3 | Principal inclusion criteria |
• Age >= 18 years • Ability to comply with the study protocol • For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs during the treatment period and for 3 months after the final dose of study treatment • Foveal center–involved macular edema due to branch retinal vein occlusion (BRVO) • Best-corrected visual acuity (BCVA) of 73 to 19 letters, inclusive (20/40 to 20/400 approximate Snellen equivalent) on Day 1 • Sufficiently clear ocular media and adequate pupillary dilatation 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 1 month before screening • Uncontrolled blood pressure • Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Day 1 • Pregnant or breastfeeding, or intending to become pregnant during the study
Ocular Exclusion Criteria for Study Eye ● History of previous episodes of macular edema due to RVO or persistent macular edema due to RVO diagnosed more than 4 months before screening ● Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than macular edema due to RVO in the study eye ● Macular laser (focal/grid) in the study eye at any time prior to Day 1 ● Panretinal photocoagulation in the study eye within 3 months prior to Day 1 or anticipated within 3 months of study start on Day 1 ● Any prior or current treatment for macular edema; macular neovascularization, including DME and nAMD; and vitreomacular-interface abnormalities, including, but not restricted to, IVT treatment with anti-VEGF, steroids, tissue plasminogen activator, ocriplasmin, C3F8, air or periocular injection ● Any prior intervention with verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or vitreo-retinal surgery including sheatotomy ● Any prior steroid implant use including dexamethasone intravitreal implant (Ozurdex) and fluocinolone acetonide intravitreal implant (Iluvien)
Ocular Exclusion Criteria for Both Eyes • Prior IVT administration of faricimab in either eye • History of idiopathic or autoimmune-associated uveitis in either eye • Active periocular, ocular or intraocular inflammation or infection (including suspected) in either eye on Day 1
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from baseline in BCVA at Week 24
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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) |
1. Change from baseline in BCVA at specified timepoints 2. Proportion of patients gaining >= 15 letters in BCVA from baseline at Week 24 3. Proportion of patients gaining >= 15, >= 10, >= 5, or > 0 letters in BCVA from baseline at specified timepoints 4. Proportion of patients avoiding a loss of >= 15, >= 10, >= 5, or > 0 letters in BCVA from baseline at specified timepoints 5. Proportion of patients achieving >= 84 letters (20/20 Snellen equivalent) in BCVA at specified timepoints 6. Proportion of patients with BCVA Snellen equivalent of 20/40 or better at specified timepoints 7. Proportion of patients with BCVA Snellen equivalent of 20/200 or worse at specified timepoints 8. Change from baseline in CST at specified timepoints 9. Change from baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) composite score at specified timepoints 10. Proportion of patients on a Q4W, every 8 weeks (Q8W), every 12 weeks (Q12W), or Q16W treatment interval at Week 72 11. Number of study drug injections received from Week 24 through Week 72 12. Incidence and severity of ocular adverse events, with severity determined according to Adverse Event Severity Grading Scale 13. Incidence and severity of non-ocular adverse events, with severity determined according to Adverse Event Severity Grading Scale 14. Plasma concentration of faricimab over time 15. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-9. Part I: Baseline to Week 24, Part II: From Week 24 to Week 72 10. At Week 72 11. From Week 24 through Week 72 12.-13. Up to Week 72 14.-15. Day 1, Week 4, 24, 28, 52, 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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
Australia |
Brazil |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
Russian Federation |
Singapore |
Taiwan |
United States |
Austria |
France |
Germany |
Hungary |
Italy |
Poland |
Portugal |
Spain |
United Kingdom |
Czechia |
Argentina |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |