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 | 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 |
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 compared to placebo To evaluate the effect of danicopan on disease progression utilizing functional measures compared to placebo 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 ≥ 70 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 4 letters; 20/20 to 20/800) using Early Treatment Diabetic Retinopathy Study charts at starting distance of 4 meters. • GA area of 0.5 to 17.76 mm2 (~0.25 to 7 disc area [DA]) per eye measured by FAF |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: • GA in either eye due to cause other than AMD. • Have previously received intravitreal anti-vascular endothelial growth factor injections in study eye. • Have previously received any complement/stem cell/gene therapy for any ophthalmological condition. • Previous participation in interventional clinical studies for treatment of drusen, nascent GA or GA (except vitamins or minerals) irrespective of route of administration (ocular or systemic) in either eye. • Presence of active ocular diseases in either eye that in the opinion of the Investigator compromises or confounds visual function or interferes with study assessments. • Known or suspected complement deficiency. • History or presence of any clinically relevant co-morbidities or any uncontrolled conditions. • Hypersensitivity to fluorescein sodium for injection, the investigational drug (danicopan) or any of its excipients.
Note: Additional inclusion/exclusion criteria may apply, per protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean rate of change from Baseline at Week 52 in the square root (sqrt) of total GA lesion area (mm/year) 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. Mean Rate Of Change From Baseline At Week 104 In The Sqrt Of The Total GA Lesion Area In The Study Eye And From Baseline At Week 52 And Week 104 In The Fellow Eye And Both Eyes Combined (Regardless Of Baseline GA Status) As Measured By FAF [Time Frame: Baseline, Week 52 and Week 104]
3. Mean Rate Of Change From Baseline At Week 52 And Week 104 In The Total GA Lesion Area In The Study Eye, The Fellow Eye, And Both Eyes Combined (Regardless Of Baseline GA Status) As Measured By FAF [Time Frame: Baseline, Week 52 and Week 104]
4. Mean Change From Baseline At Week 52 And Week 104 In The Total GA Lesion Area In The Study Eye, The Fellow Eye, And Both Eyes Combined (Regardless Of Baseline GA Status) As Measured By FAF [Time Frame: Baseline, Week 52 and Week 104]
5. Percent Change From Baseline At Week 52 And Week 104 In The Total GA Lesion Area In The Study Eye, The Fellow Eye, And Both Eyes Combined (Regardless Of Baseline GA Status) As Measured By FAF [Time Frame: Baseline, Week 52 and Week 104]
6. Mean Change From Baseline At Week 52 And Week 104 In The Sqrt Of The Total GA Lesion Area In The Study Eye, The Fellow Eye, And Both Eyes Combined (Regardless Of Baseline GA Status) As Measured By FAF [Time Frame: Baseline, Week 52 and Week 104]
7. Percent Change From Baseline At Week 52 And Week 104 In The Sqrt Of The Total GA Lesion Area In The Study Eye, The Fellow Eye, And Both Eyes Combined (Regardless Of Baseline GA Status) As Measured By FAF [Time Frame: Baseline, Week 52 and Week 104]
8. Mean Change From Baseline At Week 52 And Week 104 In Monocular Best-corrected Visual Acuity (BCVA) Scores In The Study Eye And Fellow Eye As Assessed By The Early Treatment Diabetic Retinopathy Study (ETDRS) Chart At Four Meters [Time Frame: Baseline, Week 52 and Week 104]
9. Mean Change From Baseline At Week 52 And Week 104 In Monocular Low Luminance Visual Acuity (LLVA) Scores In The Study Eye And Fellow Eye As Assessed By The ETDRS Chart At Four Meters [Time Frame: Baseline, Week 52 and Week 104]
10. Mean Change From Baseline At Week 52 And Week 104 In Low Luminance Deficit In The Study Eye And Fellow Eye [Time Frame: Baseline, Week 52 and Week 104]
11. Mean Change In National Eye Institute Visual Function Questionnaire, 25-item Version (NEI VFQ 25) Scores From Baseline At Week 52 And Week 104 [Time Frame: Baseline, Week 52 and Week 104]
12. Plasma Concentration Of Danicopan Over Time [Time Frame: Up to 4 hours postdose]
13. Ex Vivo Serum Alternative Pathway Activity [Time Frame: Up to 4 hours postdose]
14. Plasma Concentration Of Bb Fragment Of Complement Factor B [Time Frame: Up to 4 hours postdose]
15. 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 [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 | 12 |
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 |
Czechia |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Latvia |
New Zealand |
Slovakia |
Spain |
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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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 | 8 |
E.8.9.1 | In the Member State concerned days | |
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 | 1 |