E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Geographic Atrophy (AD) secondary to Age-related Macular Degeneration (AMD). |
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E.1.1.1 | Medical condition in easily understood language |
Geographic Atrophy (GA) is an advanced form of age-related macular degeneration. It is a progressive, irreversible condition of the eye that causes severe loss of visual function. |
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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 | 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 |
This is a dose finding study designed to evaluate the efficacy, safety, and pharmacokinetics of danicopan in participants with GA secondary to AMD. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of danicopan on disease progression utilizing anatomical measures in the study eye To evaluate the effect of danicopan on disease progression utilizing functional measures in the study eye To evaluate the effect of danicopan on patient reported outcomes (PROs) in patients with GA secondary to AMD To evaluate the PK and PD of danicopan in patients with GA secondary to AMD To evaluate the safety and tolerability of danicopan in patients with GA secondary to AMD |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria: • Age ≥ 60 years, male or female • Presentation of GA secondary to AMD in at least 1 eye. • Study eye must have the specified VA (range of 84 to 24 letters; 20/20 to 20/320) using Early Treatment Diabetic Retinopathy Study charts at starting distance of 4 meters. • Total GA lesion area of 0.5 to 17.76 mm2 (~0.2 to 7 disc area [DA]) per eye measured by FAF. If GA is multifocal, at least one focal lesion must be ≥ 0.5 mm2 (~0.2 DA). • The entire GA lesion must be >1 μm outside of the foveal center
Note: Additional inclusion/exclusion criteria may apply, per protocol. |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: • GA in the study eye due to cause other than AMD • Have previously received intravitreal anti-vascular endothelial growth factor injections in study eye for intraocular vascular disease • Have previously received any stem cell or gene therapy for any ophthalmological condition in either eye • Use of any investigational medicinal product (ie, participation in interventional clinical studies for any ophthalmic indications) or use of any regulatory approved treatment for GA in the study eye regardless of route of administration within the last 3 months or 5 half-lives of the last dose of the investigational or commercial product (whichever is longer) • Presence of active ocular diseases in the study eye that in the opinion of the Investigator compromises or confounds visual function or interferes with study assessments • Known or suspected complement deficiency • Hypersensitivity to the investigational drug (danicopan) or any of its excipients, or to fluorescein sodium for injection • History or presence of any medical or psychological condition that, in the opinion of the Principal Investigator, would make the patient inappropriate for the study or unable to comply with study procedures or put the patient at undue risk or confound the results of the study.
Note: Additional inclusion/exclusion criteria may apply, per protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from Baseline to Week 52 in the square root (sqrt) of total GA lesion area (mm) in the study eye as measured by fundus autofluorescence (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) |
2. Change from Baseline to Week 104 in the sqrt of the total GA lesion area in the study eye as measured by FAF [Time Frame: Baseline, Week 52 and Week 104]
3. Change from Baseline to Week 52 and Week 104 in the total GA lesion area in the study eye as measured by FAF [Time Frame: Baseline, Week 52 and Week 104]
4. Change from Baseline to Week 52 and Week 104 in macular ellipsoid zone (EZ) and outer retinal integrity in the study eye, the fellow eye, and both eyes combined as measured by SD-OCT.
5. Change from Baseline to Week 52 and Week 104 in subretinal pigment epithelium (sub-RPE) compartment/drusen/RPE complex in the study eye, fellow eye and both eyes combined as measured by SD-OCT.
6. Change from Baseline to Week 52 and Week 104 in monocular Best-corrected Visual Acuity (BCVA) scores in the study eye as assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart [Time Frame: Baseline, Week 52 and Week 104]
7. Change form Baseline to Week 52 and Week 104 in monocular Low Luminance Visual Acuity (LLVA) scores in the study eye as assessed by the ETDRS chart [Time Frame: Baseline, Week 52 and Week 104]
8. Change from Baseline to Week 52 and Week 104 in monocular low luminance deficit (BCVA-LLVA) in the study eye [Time Frame: Baseline, Week 52 and Week 104]
9. Change from Baseline to Week 52 to Week 104 in monocular reading speeds in the study eye as assessed by Minnesota Low Vision reading Test (MNRead) Acuity Charts or Radner Reading Charts [Time Frame: Baseline, Week 52 and Week 104]
10. Change from Baseline to Week 52 and Week 104 in National Eye Institute Visual Function Questionnaire (NEI VFQ -25) scores [Time Frame: Baseline, Week 52 and Week 104]
11. Plasma concentration of Danicopan over time [Time Frame: Up to 4 hours postdose]
12. Ex vivo serum Alternative Pathway activity [Time Frame: Up to 4 hours postdose]
13. Plasma Bb concentration over time [Time Frame: Up to 4 hours postdose]
14. Incidence of Treatment -emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Ocular TEAEs, SAEs, and clinical laboratory abnormalities, and events leading to discontinuation of study drug throughout the study [Time Frame: Day 1 through Week 104]
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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 | 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 | Yes |
E.6.10 | Pharmacogenetic | No |
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) | 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 | 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 | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 92 |
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 |
Canada |
Japan |
Korea, Republic of |
United Kingdom |
United States |
Czechia |
France |
Germany |
Hungary |
Italy |
Latvia |
Slovakia |
Spain |
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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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The end of the study is defined as the date the last patient completes the last visit (including the OLE, Taper, and Follow-up. |
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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 | |
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 |