E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Geographic Atrophy Secondary to Age-Related Macular Degeneration |
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E.1.1.1 | Medical condition in easily understood language |
Geographic Atrophy Secondary to Age-Related Macular Degeneration |
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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 | 10063947 |
E.1.2 | Term | Geographic atrophy |
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 evaluate the efficacy of Pegcetacoplan compared to sham injection in patients with GA secondary to AMD assessed by change in the total area of GA lesions from baseline as measured by fundus autoflourescence FAF. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of pegcetacoplan compared to sham injection in patients with GA secondary to AMD with respect to:
• Monocular maximum reading speed (study eye), as assessed by Minnesota Low- Vision Reading Test (MNREAD) or Radner Reading
Charts (in select countries)
• Functional Reading Independence (FRI) index score
• Normal luminance best corrected visual acuity score (NL-BCVA) in the study eye
• Low luminance best corrected visual acuity score (LL-BCVA) in the study eye
• Low luminance deficit (LLD) in the study eye
• Total area of GA lesion(s) in the study eye
• Monocular critical print size (study eye), as assessed by MNRead or Radner Reading Charts
• National Eye Institute Visual Functioning Questionnaire 25-Item Version (NEI VFQ-25) distance activity subscale score (in select
countries)
• Macular functional response as assessed by mesopic microperimetry |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 60 years.
2. NL-BCVA of 24 letters or better using ETDRS charts.
3. Clinical diagnosis of GA of the macula secondary to AMD as determined by the Investigator and confirmed by the Reading Center.
4. The GA lesion must meet the criteria as determined by the central reading center’s assessment of FAF imaging at screening.
5. Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit the collection of good quality images as determined by the Investigator.
6. Meets the criteria related to microperimetry.
7. Female subjects must be women of non-child-bearing potential or women of child-bearing potential with a negative pregnancy test at screening and must agree to use protocol defined methods of contraception.
8. Males with female partners of child-bearing potential must agree to use protocol defined methods of contraception
9. Willing and able to give informed consent and to comply with the study procedures and assessments. |
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E.4 | Principal exclusion criteria |
1. GA secondary to a condition other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy in either eye.
2. Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or an axial length >26 mm.
3. Any history or active CNV, associated with AMD or any other cause, including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere based on SD-OCT imaging and/or fluorescein angiography as assessed by the Reading Center.
4. Presence of an active ocular disease that in the opinion of the investigator compromises or confounds visual function, including but
not limited to, uveitis, other macular diseases (e.g. clinically significant epiretinal membrane [ERM], full thickness macular hole or uncontrolled glaucoma/ocular hypertension). Benign conditions in the opinion of the
nvestigator such as peripheral retina dystrophy are not exclusionary.
5. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization.
6. History of laser therapy in the macular region.
7. Aphakia or absence of the posterior capsule. Note: YAG laser posterior
capsulotomy for posterior capsule opacification done at least 60 days
prior to screening is not exclusionary.
8. Any ocular condition other than GA secondary to AMD that may require surgery or medical intervention during the study period or, in the opinion of the Investigator, could compromise visual function during the
study period.
9. Any contraindication to IVT injection including current ocular or periocular infection.
10. History of prior intravitreal injection.
11. Prior participation in another interventional clinical study for IVT.
therapies in either eye (including subjects receiving sham).
12. Prior participation in another interventional clinical study for GA in
either eye including investigational oral medication and placebo).
13. Prior participation in another interventional clinical study for
geographic atrophy in either eye including investigational oral medication and placebo.
14. Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of study
treatment.
15. Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over the 24-month treatment period unlikely, or would make the subject an unsafe study candidate.
16. Any screening laboratory value (hematology, serum chemistry or
urinalysis) that in the opinion of the Investigator is clinically significant and not suitable for study participation.
17. Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to Pegcetacoplan or any of the excipients in
Pegcetacoplan solution. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Month 12 in total area of GA lesion(s) in the study eye (in mm2) based on FAF.
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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) |
• Change from baseline in maximum monocular reading speed (study
eye), as assessed by MNRead or Radner Reading Charts
• Change from baseline in FRI index score
• Change from baseline in NL-BCVA as assessed by ETDRS chart.
• Change from baseline in LL-BCVA as assessed by ETDRS chart.
• Change from baseline in LLD
• Change from baseline at each planned assessment in the total area of GA lesion(s) in the study eye (in mm2) as assessed by FAF.
• Change from baseline in monocular critical print size (study eye), as assessed by MNRead or Radner Reading Charts, (in selected countries).
• Change from baseline in the NEI VFQ-25 distance activity subscale score (in select countries)
• Number of scotomatous points assessed by mesopic microperimetry or the evaluation of the macular functional response.
• Change in macular sensitivity as assessed by mesopic microperimetry for the evaluation of the macular functional response. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Month 24 - Change from baseline in maximum monocular reading speed MNRead or Radner Reading Charts
• Month 24 - Change from baseline in FRI index score
• Month 24 - Change from baseline in NL-BCVA
• Month 12, Month 24 - Change from baseline in LL-BCVA
• Month 12, Month 24 - Change from baseline in LLD
• Month 12, Month 24 - Change in baseline in the total area of GA lesion(s)
• Month 12, Month 24 - Change from baseline in monocular critical print size
• Month 12, Month 24 - Change from baseline in NEI VFQ-25 distance activity subscale score
• Months 6, 12, 18, 24 - Number of scotomatous points and change in macular sensitivity, as assessed by mesopic microperimetry for the evaluation of the macular functional response. |
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Canada |
Czechia |
Germany |
Israel |
Italy |
Netherlands |
New Zealand |
Poland |
Spain |
United Kingdom |
United States |
France |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |