A Study of Danicopan in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

29 Apr 2022 → 21 Jan 2025

Decision date (initial)

2024-06-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Alexion Pharmaceuticals, Inc

External identifiers

EU CT number

2023-508571-37-00

EudraCT number

2021-001198-22

ClinicalTrials.gov

NCT05019521

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacokinetic, Safety, Dose response

This is a dose finding study designed to evaluate the efficacy, safety, and pharmacokinetics of danicopan in participants with GA secondary to AMD.

Secondary objectives 5

1. To evaluate the effect of danicopan on disease progression utilizing anatomical measures in the study eye
2. To evaluate the effect of danicopan on disease progression utilizing functional measures in the study eye
3. To evaluate the effect of danicopan on patient reported outcomes (PROs) in patients with GA secondary to AMD
4. To evaluate the PK and PD of danicopan in patients with GA secondary to AMD
5. To evaluate the safety and tolerability of danicopan in patients with GA secondary to AMD

Conditions and MedDRA coding

Geographic atrophy (GA) secondary to Age-related Macular Degeneration (AMD)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 60 years, male or female.
2. Presentation of GA secondary to AMD in at least 1 eye.
3. 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.
4. 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).
5. The entire GA lesion must be >1 μm outside of the foveal center.

Exclusion criteria 8

1. GA in the study eye due to cause other than AMD.
2. Have previously received intravitreal anti-vascular endothelial growth factor injections in study eye for intraocular vascular disease.
3. Have previously received any stem cell or gene therapy for any ophthalmological condition in either eye.
4. 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).
5. 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.
6. Known or suspected complement deficiency.
7. Hypersensitivity to the investigational drug (danicopan) or any of its excipients, or to fluorescein sodium for injection.
8. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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)

Secondary endpoints 12

1. 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]
2. 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]
3. 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
4. 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.
5. 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]
6. 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 [Time Frame: Baseline, Week 52 and Week 104]
7. 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]
8. Change form 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 Chart [Time Frame: Baseline, Week 52 and Week 104]
9. 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]
10. Plasma concentration of Danicopan over time [Time Frame: Up to 4 hours postdose]
11. PD Biomarkers, Ex Vivo Serum Alternative Pathway Activity, and Plasma Bb Concentration Over Time [Time Frame: Up to 4 hours postdose]
12. 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]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Third parties 13

Locations

8 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications