A Phase 2, Double-Masked, Placebo-Controlled, Dose Range Finding Study of Danicopan (ALXN2040) in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 365
- Locations
- 1
- Primary Endpoint
- Rate of Change From Baseline to Week 52 in the Square Root (Sqrt) of Total Geographic Atrophy (GA) Lesion Area in the Study Eye as Measured by Fundus Autofluorescence (FAF)
Study Overview
Brief Summary
This is a dose finding study designed to evaluate the efficacy, safety, and pharmacokinetics of danicopan in participants with GA secondary to AMD. The study consists of a Screening Period of up to 6 weeks, a 104-week masked Treatment Period, followed by a 30-day Follow-up after the last dose. This study will have 4 treatments arms: 100 milligrams (mg) twice daily (bid), 200 mg bid, 400 mg once daily (qd), and matching placebo.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Masking of treatment allocation will be observed until Week 104.
Eligibility Criteria
- Ages
- 60 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Vaccination for Neisseria meningitidis.
- •Capable of giving signed informed consent.
- •Presentation of GA secondary to AMD in at least 1 eye
- •The entire GA lesion must be > 1 μm outside of the foveal center
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/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.
- •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.
- •Hypersensitivity to fluorescein sodium for injection, the investigational drug (danicopan) or any of its excipients.
- •Note: Additional inclusion/exclusion criteria may apply, per protocol.
Arms & Interventions
Danicopan: 100 mg
Participants will receive danicopan 100 mg bid during the masked Treatment Period. Once the optimal dose is identified, participants who have at least 52 weeks of treatment will be switched to the optimal dose for the remainder of the study.
Intervention: Danicopan (Drug)
Danicopan: 200 mg
Participants will receive danicopan 200 mg bid during the masked Treatment Period. Once the optimal dose is identified, participants who have at least 52 weeks of treatment will be switched to the optimal dose for the remainder of the study.
Intervention: Danicopan (Drug)
Danicopan: 400 mg
Participants will receive danicopan 400 mg qd during the masked Treatment Period. Once the optimal dose is identified, participants who have at least 52 weeks of treatment will be switched to the optimal dose for the remainder of the study.
Intervention: Danicopan (Drug)
Placebo
Participants will receive matching placebo and will be re-randomized to one of the active treatment groups at Week 52, or to the optimal dose, if already identified.
Intervention: Danicopan (Drug)
Placebo
Participants will receive matching placebo and will be re-randomized to one of the active treatment groups at Week 52, or to the optimal dose, if already identified.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Rate of Change From Baseline to Week 52 in the Square Root (Sqrt) of Total Geographic Atrophy (GA) Lesion Area in the Study Eye as Measured by Fundus Autofluorescence (FAF)
Time Frame: Baseline, Week 52
FAF provides high-contrast retinal images particularly valuable for the detection of atrophic areas. FAF images of the study eye were taken and sent to the reading center for total GA lesion area measurement. The total GA lesion area (square millimeter \[mm\^2\]) was transformed into sqrt (millimeter \[mm\]). Greater area affected means a worse outcome than smaller area affected. The rate of change from Baseline (mm/year) for each treatment group was estimated based on the coefficients for time and the interaction of time and treatment from the mixed models for repeated measures (MMRM). MMRM analysis included the change from Baseline at post-baseline visit in the sqrt GA lesion area as dependent variable.
Secondary Outcomes
- Change From Baseline to Week 104 in the Sqrt of the Total GA Lesion Area in the Study Eye as Measured by FAF(Baseline, Week 104)
- Change From Baseline to Week 52 and Week 104 in the Total GA Lesion Area in the Study Eye as Measured by FAF(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Percent Macular Ellipsoid Zone (EZ) Total Attenuation in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by Spectral-domain Optical Coherence Tomography (SD-OCT)(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Percent Macular EZ Partial Attenuation in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Outer Nuclear Layer (ONL) - Retinal Pigment Epithelium (RPE) Mean Central 1 mm Subfield Thickness in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in ONL-RPE Mean Central Macular 2 mm Subfield Thickness in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Ellipsoid Zone (EZ) - (RPE) Macular Volume in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in EZ-RPE Mean Central 1 mm Subfield Thickness in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Percent Central 1 mm Subfield EZ Partial Attenuation in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in EZ-RPE Mean Central Macular 2 mm Thickness in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Percent Central 1 mm Subfield EZ Total Attenuation in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Percent Central Macular 2 mm Subfield EZ Total Attenuation in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Percent Central Macular 2 mm Subfield EZ Partial Attenuation in the Study Eye, the Fellow Eye, and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Sub-RPE Central 1 mm Subfield Mean Thickness in the Study Eye, Fellow Eye and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Sub-RPE Central Macular 2 mm Subfield Mean Thickness in the Study Eye, Fellow Eye and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Panmacular Sub-RPE Volume in the Study Eye, Fellow Eye and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Percent Macular Total RPE Attenuation in the Study Eye, Fellow Eye and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Percent Central 1 mm Subfield Total RPE Attenuation in the Study Eye, Fellow Eye and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Percent Central Macular 2 mm Subfield Total RPE Attenuation in the Study Eye, Fellow Eye and Both Eyes Combined as Measured by SD-OCT(Baseline, Week 52 and Week 104)
- 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(Baseline, Week 52 and Week 104)
- Change From 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(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in Low Luminance Deficit (LLD) (BCVA-LLVA) Score in the Study Eye(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 And 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(Baseline, Week 52 and Week 104)
- Change From Baseline to Week 52 and Week 104 in National Eye Institute Visual Function Questionnaire (NEI VFQ-25) Composite Scores(Baseline, Week 52 and Week 104)
- Plasma Concentration of Danicopan(Day 1 and Week 52)
- Change From Baseline in Ex Vivo Serum Alternative Pathway (AP) Activity(Week 52 (pre-dose, 2 hours post-dose))
- Change From Baseline in Plasma Bb Fragment of Complement Factor B (Bb) Concentration(Baseline, Week 52 (pre-dose))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading To Discontinuation of Study Drug Throughout the Study(Day 1 through Week 108)