Evaluation of AGN-150998 in Exudative Age-related Macular Degeneration (AMD)

Phase 2

Completed

• Conditions: Age-related Macular Degeneration
• Interventions: Drug: AGN-150998; Drug: ranibizumab; Other: Sham Injection

• Registration Number: NCT01397409
• Lead Sponsor: Allergan

Brief Summary

This study is conducted in 3 stages. Stage 1 is an open-label, dose-escalation assessment of the safety of AGN-150998 administered as a single intravitreal injection to patients with advanced exudative Age-related Macular Degeneration (AMD). Stage 2 and Stage 3 are randomized, double-masked, comparisons of the safety and treatment effects on retinal edema and best-corrected visual acuity (BCVA) of AGN-150998 and ranibizumab in treatment-naive patients with exudative AMD. Study medication is administered as needed in Stage 2 and with a fixed-dosing schedule in Stage 3. The study objectives are (1) to identify the highest tolerated dose of AGN-150998, (2) to assess the safety and duration of treatment effects on retinal edema and BCVA, and (3) to characterize the systemic pharmacokinetic profile of AGN-150998.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-07-18
• Study First Submitted QC: 2011-07-18
• Study First Posted: 2011-07-19
• Study Start: 2011-09-01
• Primary Completion: 2014-03-31
• Study Completion: 2014-04-30
• Results First Submitted: 2015-06-02
• Results First Submitted QC: 2015-06-02
• Results First Posted: 2015-06-18
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-09
• Last Update Posted: 2019-04-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 271

Inclusion Criteria

• Exudative age-related macular degeneration
• Best-corrected visual acuity between 20/32 and 20/320 in the study eye

Exclusion Criteria

• Near-sightedness of 8 diopters or more
• Uncontrolled glaucoma in the study eye
• Cataract surgery or Lasik within the last 3 months
• Any active ocular infection or inflammation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stage 1: AGN-150998 1.0 mg	AGN-150998	Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection.
Stage 1: AGN-150998 3.0 mg	AGN-150998	Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection.
Stage 2: AGN-150998 4.2 mg	AGN-150998	Stage 2: AGN-150998 4,2 mg (highest tolerated dose from Stage 1) given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.
Stage 3: AGN-150998 1.0 mg	Sham Injection	Stage 3: AGN-150998 1.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.
Stage 1: AGN-150998 2.0 mg	AGN-150998	Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection.
Stage 3: AGN-150998 2.0 mg	Sham Injection	Stage 3: AGN-150998 2.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.
Stage 3: AGN-150998 1.0 mg	AGN-150998	Stage 3: AGN-150998 1.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.
Stage 1: AGN-150998 4.2 mg	AGN-150998	Stage 1: AGN-150998 4.2.mg given as a single intravitreal injection.
Stage 2: AGN-150998 3.0 mg	AGN-150998	Stage 2: AGN-150998 3.0 mg (one dose below highest tolerated dose) from Stage 1 given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.
Stage 3: AGN-150998 2.0 mg	AGN-150998	Stage 3: AGN-150998 2.0 mg given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16.
Stage 2: ranibizumab 0.5 mg	ranibizumab	Stage 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.
Stage 3: ranibizumab 0.5 mg	ranibizumab	Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks.

Primary Outcome Measures

Name	Time	Method
Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye	Baseline, Week 4	CRT was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from Baseline indicated improvement.
Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye	Baseline, Week 16	BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Highest Tolerated Dose (HTD) of AGN-150998	24 Weeks	Stage 1 evaluated the safety of a single intravitreal injection of AGN-150998 with doses ranging from 1.0 to 4.2 mg.
Stage 2: Time Between Baseline Treatment and Recurrence of Active Disease	Baseline, Week 16	Recurrence of Active Disease was based on Best Corrected Visual Acuity (BCVA), Central Retinal Thickness (CRT) values as evaluated by the Central Reading Center (CRC) and the investigator assessments of haemorrhage.

Secondary Outcome Measures

Name	Time	Method
Stage 2: Time Between Second Treatment and Recurrence of Active Disease	32 Weeks	Recurrence of active disease is defined as the time in days to escape to standard of care. Time is calculated as (date of Escaping to Standard of Care/Censoring minus the date of the Second Injection) +1.
Stage 2: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye	Baseline, Week 4	CRT was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from Baseline indicated improvement.
Stage 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye	Baseline, Week 4	BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Stage 3: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye	Baseline, Week 4	CRT was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from Baseline indicated improvement.
Stage 3: Change From Baseline in BCVA in the Study Eye	Baseline, Week 4	BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.