E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular age-related macular degeneration |
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E.1.1.1 | Medical condition in easily understood language |
Neovascular Age-related macular degeneration (nAMD), also known as wet AMD, is a medical condition which may result in distortion and potentially irreversible loss of the central 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 | PT |
E.1.2 | Classification code | 10071129 |
E.1.2 | Term | Neovascular age-related macular degeneration |
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 IVT (intravitreal) injections of faricimab on change in best-corrected visual acuity (BCVA) |
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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 study drug administration
• To evaluate the efficacy of faricimab on anatomical outcome measures using optical coherence tomography (OCT) and fundus fluorescein angiography (FFA)
• To evaluate the ocular and non-ocular safety and tolerability of faricimab
• To characterize the systemic pharmacokinetics of faricimab
• To evaluate the immune response to faricimab
• To evaluate potential effects of anti-drug antibody (ADA)s |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 50 years
- Ability to comply with the study protocol
- For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 3 months after the final dose of study treatment
- Treatment-naïve choroidal neovascularization (CNV) secondary to AMD (nAMD) in the study eye
- BCVA of 20/32 to 20/320 (letter score of 78 to 24) in the study eye at the initiation of treatment |
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E.4 | Principal exclusion criteria |
- Uncontrolled blood pressure
- Pregnancy or breastfeeding, or intention to become pregnant during the study
- CNV due to causes other than AMD in the study eye
- Any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye
- Presence at screening of central serous chorioretinopathy in the study eye
- Retinal pigment epithelial tear involving the macula on Day 1 in the study eye
- On FFA/ Color fundus photograph:
o Subretinal hemorrhage of > 50% of the total lesion area and/or that involves the fovea
o Fibrosis or atrophy of > 50% of the total lesion area and/or that involves the fovea
- Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study
- Current vitreous hemorrhage on Day 1 in the study eye
- Uncontrolled glaucoma in the study eye
- Spherical equivalent of refractive error demonstrating more than 8 diopters of myopia in the study eye
- Any prior or concomitant treatment for CNV or vitreomacular-interface abnormalities in the study eye
- Any cataract surgery or treatment for complications of cataract surgery with steroids or YAG laser capsulotomy in the study eye within 3 months prior to Day 1
- Any other intraocular surgery in the study eye
- Prior periocular pharmacological or IVT treatment for other retinal diseases in the study eye
- Prior IVT administration of faricimab in either eye
- Active ocular inflammation or suspected or active ocular or periocular infection in either eye |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in BCVA from baseline to average at Weeks 40, 44 and 48
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline (Day 1), Weeks 40, 44, and 48 |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in BCVA over time
2. Proportion of patients gaining >= 15, >= 10, >= 5, or >= 0 letters in BCVA from baseline over time
3. Proportion of patients avoiding loss of >= 15, >= 10, >=5, or >= 0 letters in BCVA from baseline over time
4. Proportion of patients with BCVA Snellen equivalent of 20/40 or better over time
5. Proportion of patients gaining >= 15 letters or achieving BCVA of >= 84 letters over time
6. Proportion of patients with BCVA Snellen equivalent of 20/200 or worse over time
7. Proportion of patients on different treatment intervals at Weeks 48, 60, and 112
8. Number of study drug injections received through Weeks 48, 60, and 112
9. Change from baseline in CST based on an average at Weeks 40, 44, and 48
10. Change from baseline in CST over time
11. Proportion of patients with absence of intraretinal fluid over time
12. Proportion of patients with absence of subretinal fluid over time
13. Proportion of patients with absence of intraretinal and subretinal fluid over time
14. Proportion of patients with absence of intraretinal cysts over time
15. Proportion of patients with absence of pigment epithelium detachment over time
16. Change from baseline in total area of CNV lesion at Week 48 and Week 112
17. Change from baseline in total area of leakage at Week 48 and Week 112
18. Incidence and severity of ocular adverse events
19. Incidence and severity of non-ocular adverse events
20. Plasma concentration of faricimab over time
21. Presence of ADAs during the study relative to the presence of ADAs at baseline
22. Relationship between ADA status and efficacy, safety, or pharmacokinetic endpoints |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-6. Baseline to Week 112
7-8. Week 48, 60, and 112
9-15. Baseline to Week 112
16-17. Baseline, Week 48 and 112
18-19. Up to Week 112
20. Week 1, 4, 16, 20, 48, 76, 112
21-22. Week 1, 4, 20, 48, 76, 112
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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 | 31 |
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 |
Brazil |
Canada |
Germany |
Hungary |
Israel |
Italy |
Japan |
Mexico |
Netherlands |
Poland |
Russian Federation |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |