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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Allergan
ClinicalTrials.gov Identifier:
NCT01397409
First received: July 18, 2011
Last updated: June 2, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Age-related Macular Degeneration
Drug: AGN-150998
Drug: ranibizumab
Other: Sham Injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Allergan:

Primary Outcome Measures:
  • Highest Tolerated Dose (HTD) of AGN-150998 [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Stage 1 evaluated the safety of a single intravitreal injection of AGN-150998 with doses ranging from 1.0 to 4.2 mg.

  • Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
    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: Time Between Baseline Treatment and Recurrence of Active Disease [ Time Frame: Baseline, Week 16 ] [ Designated as safety issue: No ]
    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.

  • Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye [ Time Frame: Baseline, Week 16 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Stage 2: Time Between Second Treatment and Recurrence of Active Disease [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
    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.


Enrollment: 271
Study Start Date: September 2011
Study Completion Date: April 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stage 1: AGN-150998 4.2 mg
Stage 1: AGN-150998 4.2.mg given as a single intravitreal injection.
Drug: AGN-150998
AGN-150998 Intravitreal injection.
Experimental: Stage 1: AGN-150998 3.0 mg
Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection.
Drug: AGN-150998
AGN-150998 Intravitreal injection.
Experimental: Stage 1: AGN-150998 2.0 mg
Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection.
Drug: AGN-150998
AGN-150998 Intravitreal injection.
Experimental: Stage 1: AGN-150998 1.0 mg
Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection.
Drug: AGN-150998
AGN-150998 Intravitreal injection.
Experimental: Stage 2: AGN-150998 4.2 mg
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.
Drug: AGN-150998
AGN-150998 Intravitreal injection.
Experimental: Stage 2: AGN-150998 3.0 mg
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.
Drug: AGN-150998
AGN-150998 Intravitreal injection.
Active Comparator: Stage 2: ranibizumab 0.5 mg
Stage 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.
Drug: ranibizumab
Ranibizumab 0.5 mg given by intravitreal injection.
Other Name: Lucentis®
Experimental: Stage 3: AGN-150998 2.0 mg
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.
Drug: AGN-150998
AGN-150998 Intravitreal injection.
Other: Sham Injection
Stage 3: Sham injection at Weeks 12 and 16.
Experimental: Stage 3: AGN-150998 1.0 mg
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.
Drug: AGN-150998
AGN-150998 Intravitreal injection.
Other: Sham Injection
Stage 3: Sham injection at Weeks 12 and 16.
Active Comparator: Stage 3: ranibizumab 0.5 mg
Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks.
Drug: ranibizumab
Ranibizumab 0.5 mg given by intravitreal injection.
Other Name: Lucentis®

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01397409

Locations
United States, Arizona
Phoenix, Arizona, United States
Australia, New South Wales
Sydney, New South Wales, Australia
Austria
Vienna, Austria
France
Créteil, France
Germany
Bonn, Germany
Israel
Tel Aviv, Israel
Italy
Firenze, Italy
Switzerland
Binningen, Switzerland
Sponsors and Collaborators
Allergan
Investigators
Study Director: Medical Director Allergan
  More Information

No publications provided

Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT01397409     History of Changes
Other Study ID Numbers: 150998-001, 2011-002526-43, REACH Study
Study First Received: July 18, 2011
Results First Received: June 2, 2015
Last Updated: June 2, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Macular Degeneration
Eye Diseases
Retinal Degeneration
Retinal Diseases

ClinicalTrials.gov processed this record on July 01, 2015