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

Sponsor
Allergan (Industry)
Overall Status
Completed
CT.gov ID
NCT01397409
Collaborator
(none)
271
Enrollment
8
Locations
10
Arms
31.9
Actual Duration (Months)
33.9
Patients Per Site
1.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
271 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Actual Study Start Date :
Sep 1, 2011
Actual Primary Completion Date :
Mar 31, 2014
Actual Study Completion Date :
Apr 30, 2014

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • Lucentis®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    Secondary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Phoenix Arizona United States
    2 Sydney New South Wales Australia
    3 Vienna Austria
    4 Créteil France
    5 Bonn Germany
    6 Tel Aviv Israel
    7 Firenze Italy
    8 Binningen Switzerland

    Sponsors and Collaborators

    • Allergan

    Investigators

    • Study Director: Medical Director, Allergan

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Allergan
    ClinicalTrials.gov Identifier:
    NCT01397409
    Other Study ID Numbers:
    • 150998-001
    • 2011-002526-43
    • REACH Study
    First Posted:
    Jul 19, 2011
    Last Update Posted:
    Apr 16, 2019
    Last Verified:
    Apr 1, 2019
    Additional relevant MeSH terms:
    Macular Degeneration
    Ranibizumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Stage 1: AGN-150998 4.2 mg Stage 1: AGN-150998 3.0 mg Stage 1: AGN-150998 2.0 mg Stage 1: AGN-150998 1.0 mg Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg Stage 3: AGN-150998 2.0 mg Stage 3: AGN-150998 1.0 mg Stage 3: Ranibizumab 0.5 mg
    Arm/Group Description Stage 1: AGN-150998 4.2 mg given as a single intravitreal injection. Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection. Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection. 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 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 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: 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 given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16. Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks
    Period Title: Stage 1
    STARTED 9 6 6 3 0 0 0 0 0 0
    COMPLETED 9 6 6 3 0 0 0 0 0 0
    NOT COMPLETED 0 0 0 0 0 0 0 0 0 0
    Period Title: Stage 1
    STARTED 0 0 0 0 67 58 58 0 0 0
    COMPLETED 0 0 0 0 59 54 58 0 0 0
    NOT COMPLETED 0 0 0 0 8 4 0 0 0 0
    Period Title: Stage 1
    STARTED 0 0 0 0 0 0 0 23 25 16
    COMPLETED 0 0 0 0 0 0 0 21 25 16
    NOT COMPLETED 0 0 0 0 0 0 0 2 0 0

    Baseline Characteristics

    Arm/Group Title Stage 1: AGN-150998 4.2 mg Stage 1: AGN-150998 3.0 mg Stage 1: AGN-150998 2.0 mg Stage 1: AGN-150998 1.0 mg Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg Stage 3: AGN-150998 2.0 mg Stage 3: AGN-150998 1.0 mg Stage 3: Ranibizumab 0.5 mg Total
    Arm/Group Description Stage 1: AGN-150998 4.2 mg given as a single intravitreal injection. Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection. Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection. 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 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 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: 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 given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16. Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks Total of all reporting groups
    Overall Participants 9 6 6 3 67 58 58 23 25 16 271
    Age (Years) [Mean (Full Range) ]
    Mean (Full Range) [Years]
    82.3
    75.3
    79.3
    67.7
    80.4
    78.6
    78.5
    77.9
    75.5
    76.5
    77.2
    Sex: Female, Male (Count of Participants)
    Female
    5
    55.6%
    2
    33.3%
    4
    66.7%
    2
    66.7%
    34
    50.7%
    35
    60.3%
    38
    65.5%
    13
    56.5%
    18
    72%
    8
    50%
    159
    58.7%
    Male
    4
    44.4%
    4
    66.7%
    2
    33.3%
    1
    33.3%
    33
    49.3%
    23
    39.7%
    20
    34.5%
    10
    43.5%
    7
    28%
    8
    50%
    112
    41.3%

    Outcome Measures

    1. Primary Outcome
    Title Highest Tolerated Dose (HTD) of AGN-150998
    Description Stage 1 evaluated the safety of a single intravitreal injection of AGN-150998 with doses ranging from 1.0 to 4.2 mg.
    Time Frame 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population included all treated participants.
    Arm/Group Title Stage 1 All Participants
    Arm/Group Description Participants in Stage 1 received an intravitreal injection of AGN-150998 with doses ranging from 1.0 to 4.2 mg.
    Measure Participants 24
    Number [mg]
    4.2
    2. Primary Outcome
    Title Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye
    Description 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.
    Time Frame Baseline, Week 4

    Outcome Measure Data

    Analysis Population Description
    Safety population included all treated participants.
    Arm/Group Title Stage 1: AGN-150998 4.2 mg Stage 1: AGN-150998 3.0 mg Stage 1: AGN-150998 2.0 mg Stage 1: AGN-150998 1.0 mg
    Arm/Group Description Stage 1: AGN-150998 4.2 mg given as a single intravitreal injection. Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection. Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection
    Measure Participants 9 6 6 3
    Baseline
    527.6
    (126.79)
    540.3
    (284.34)
    500.3
    (155.65)
    564.3
    (115.68)
    Change from Baseline at Week 4 (n=9,6,6,2)
    -185.4
    (161.23)
    -239.5
    (234.03)
    -212.3
    (182.94)
    -113.5
    (135.06)
    3. Primary Outcome
    Title Stage 2: Time Between Baseline Treatment and Recurrence of Active Disease
    Description 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.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Population included all treated participants who received all scheduled treatments.
    Arm/Group Title Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg
    Arm/Group Description 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 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 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.
    Measure Participants 65 57 57
    Median (Inter-Quartile Range) [days]
    59.0
    57.0
    57.0
    4. Primary Outcome
    Title Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
    Description 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.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    Modified-Intent-to-Treat (mITT) Population
    Arm/Group Title Stage 3: AGN-150998 2.0 mg Stage 3: AGN-150998 1.0 mg Stage 3: Ranibizumab 0.5 mg
    Arm/Group Description 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 given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16 Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks.
    Measure Participants 23 25 16
    Baseline
    58.5
    (14.29)
    58.4
    (13.49)
    60.4
    (16.41)
    Change from Baseline at Week 16
    8.2
    (7.89)
    6.3
    (7.81)
    5.3
    (11.08)
    5. Secondary Outcome
    Title Stage 2: Time Between Second Treatment and Recurrence of Active Disease
    Description 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.
    Time Frame 32 Weeks

    Outcome Measure Data

    Analysis Population Description
    mITT Population
    Arm/Group Title Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg
    Arm/Group Description 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 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 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.
    Measure Participants 62 55 58
    Median (Inter-Quartile Range) [days]
    85.0
    112.0
    111.0
    6. Secondary Outcome
    Title Stage 2: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye
    Description 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.
    Time Frame Baseline, Week 4

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Population included all treated participants who received all scheduled treatments.
    Arm/Group Title Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg
    Arm/Group Description 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 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 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.
    Measure Participants 65 57 57
    Baseline
    524.6
    (170.71)
    507.3
    (139.88)
    497.1
    (122.04)
    Change from Baseline at Week 4 (n=61,56,57)
    -179.5
    (123.76)
    -155.3
    (109.13)
    -157.3
    (121.95)
    7. Secondary Outcome
    Title Stage 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
    Description 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.
    Time Frame Baseline, Week 4

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Population included all treated participants who received all scheduled treatments.
    Arm/Group Title Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg
    Arm/Group Description 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 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 2: ranibizumab 0.5 mg given as a single intravitreal injection at baseline. A second intravitreal injection will be given by week 16.
    Measure Participants 65 57 57
    Baseline
    54.5
    (13.90)
    52.7
    (12.62)
    55.4
    (13.00)
    Change from Baseline at Week 4 (n=62,56,57)
    4.7
    (9.71)
    8.4
    (11.51)
    5.9
    (64.0)
    8. Secondary Outcome
    Title Stage 3: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye
    Description 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.
    Time Frame Baseline, Week 4

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Population included all treated participants who received all scheduled treatments.
    Arm/Group Title Stage 3: AGN-150998 2.0 mg Stage 3: AGN-150998 1.0 mg Stage 3: Ranibizumab 0.5 mg
    Arm/Group Description 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 given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16 Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks.
    Measure Participants 23 25 16
    Baseline
    466.0
    (125.96)
    526.1
    (165.09)
    463.3
    (94.56)
    Change from Baseline at Week 4
    -119.8
    (68.50)
    -168.3
    (137.07)
    -98.4
    (65.22)
    9. Secondary Outcome
    Title Stage 3: Change From Baseline in BCVA in the Study Eye
    Description 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.
    Time Frame Baseline, Week 4

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Population included all treated participants who received all scheduled treatments.
    Arm/Group Title Stage 3: AGN-150998 2.0 mg Stage 3: AGN-150998 1.0 mg Stage 3: Ranibizumab 0.5 mg
    Arm/Group Description 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 given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16 Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks.
    Measure Participants 23 25 16
    Baseline
    58.5
    (14.29)
    58.4
    (13.49)
    60.4
    (16.41)
    Change from Baseline at Week 4
    5.0
    (7.40)
    4.6
    (5.98)
    3.9
    (6.01)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Stage 1: AGN-150998 4.2 mg Stage 1: AGN-150998 3.0 mg Stage 1: AGN-150998 2.0 mg Stage 1: AGN-150998 1.0 mg Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg Stage 3: AGN-150998 2.0 mg Stage 3: AGN-150998 1.0 mg Stage 3: Ranibizumab 0.5 mg
    Arm/Group Description Stage 1: AGN-150998 4.2 mg given as a single intravitreal injection. Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection. Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection. 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 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 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: 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 given as intravitreal injections at Baseline, Weeks 4 and 8, followed by sham injections at Weeks 12 and 16. Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks
    All Cause Mortality
    Stage 1: AGN-150998 4.2 mg Stage 1: AGN-150998 3.0 mg Stage 1: AGN-150998 2.0 mg Stage 1: AGN-150998 1.0 mg Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg Stage 3: AGN-150998 2.0 mg Stage 3: AGN-150998 1.0 mg Stage 3: Ranibizumab 0.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Stage 1: AGN-150998 4.2 mg Stage 1: AGN-150998 3.0 mg Stage 1: AGN-150998 2.0 mg Stage 1: AGN-150998 1.0 mg Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg Stage 3: AGN-150998 2.0 mg Stage 3: AGN-150998 1.0 mg Stage 3: Ranibizumab 0.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/9 (0%) 0/6 (0%) 1/6 (16.7%) 0/3 (0%) 11/67 (16.4%) 6/58 (10.3%) 5/58 (8.6%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Cardiac disorders
    Aortic valve stenosis 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Angina pectoris 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 1/58 (1.7%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Myocardial infarction 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Eye disorders
    Uveitus 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 3/67 (4.5%) 2/58 (3.4%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Anterior chamber inflammation 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 2/67 (3%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Vitritis 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 1/58 (1.7%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Choroiditis 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Glaucoma 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Optic ischaemic neuropathy 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Retinal artery occlusion 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Gastrointestinal disorders
    Pancreatitis acute 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Duodenal ulcer haemorrhage 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 1/58 (1.7%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Gastric ulcer haemorrhage 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Hepatobiliary disorders
    Cholecystitis acute 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Infections and infestations
    Pneumonia 0/9 (0%) 0/6 (0%) 1/6 (16.7%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Endophthalmitis 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Atypical pneumonia 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 1/58 (1.7%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Rectal adenocarcinoma 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Rectal cancer 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Renal cell carcinoma 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Squamous cell carcinoma of skin 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Nervous system disorders
    Cerebrovascular accident 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 1/58 (1.7%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Renal and urinary disorders
    Renal failure acute 0/9 (0%) 0/6 (0%) 1/6 (16.7%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Vascular disorders
    Temporal arteritis 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Other (Not Including Serious) Adverse Events
    Stage 1: AGN-150998 4.2 mg Stage 1: AGN-150998 3.0 mg Stage 1: AGN-150998 2.0 mg Stage 1: AGN-150998 1.0 mg Stage 2: AGN-150998 4.2 mg Stage 2: AGN-150998 3.0 mg Stage 2: Ranibizumab 0.5 mg Stage 3: AGN-150998 2.0 mg Stage 3: AGN-150998 1.0 mg Stage 3: Ranibizumab 0.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/9 (33.3%) 5/6 (83.3%) 4/6 (66.7%) 2/3 (66.7%) 51/67 (76.1%) 35/58 (60.3%) 35/58 (60.3%) 10/23 (43.5%) 15/25 (60%) 9/16 (56.3%)
    Blood and lymphatic system disorders
    Iron deficiency anaemia 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Cardiac disorders
    Palpitations 0/9 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Ventricular extrasystoles 0/9 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Eye disorders
    Anterior chamber inflammation 1/9 (11.1%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 2/67 (3%) 1/58 (1.7%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Retinal pigment epithelial tear 1/9 (11.1%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 1/58 (1.7%) 0/58 (0%) 1/23 (4.3%) 1/25 (4%) 0/16 (0%)
    Conjunctival haemorrhage 0/9 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/3 (33.3%) 9/67 (13.4%) 3/58 (5.2%) 5/58 (8.6%) 1/23 (4.3%) 2/25 (8%) 0/16 (0%)
    Eye irritation 0/9 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/3 (0%) 5/67 (7.5%) 2/58 (3.4%) 2/58 (3.4%) 1/23 (4.3%) 1/25 (4%) 0/16 (0%)
    Anterior chamber cell 0/9 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 2/67 (3%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Anterior chamber flare 0/9 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Eye pain 0/9 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 6/67 (9%) 3/58 (5.2%) 4/58 (6.9%) 2/23 (8.7%) 1/25 (4%) 1/16 (6.3%)
    Hyalosis asteroid 0/9 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Macular oedema 0/9 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Foreign body sensation in eyes 0/9 (0%) 0/6 (0%) 1/6 (16.7%) 0/3 (0%) 4/67 (6%) 0/58 (0%) 1/58 (1.7%) 0/23 (0%) 1/25 (4%) 1/16 (6.3%)
    Retinal haemorrhage 0/9 (0%) 0/6 (0%) 0/6 (0%) 1/3 (33.3%) 6/67 (9%) 3/58 (5.2%) 4/58 (6.9%) 0/23 (0%) 3/25 (12%) 2/16 (12.5%)
    Vitreous detachment 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 5/67 (7.5%) 6/58 (10.3%) 2/58 (3.4%) 2/23 (8.7%) 2/25 (8%) 0/16 (0%)
    Visual acuity reduced 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 5/67 (7.5%) 3/58 (5.2%) 3/58 (5.2%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Vitritis 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 3/58 (5.2%) 0/58 (0%) 0/23 (0%) 1/25 (4%) 0/16 (0%)
    Vitreous floaters 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 3/58 (5.2%) 0/58 (0%) 1/23 (4.3%) 3/25 (12%) 1/16 (6.3%)
    Dry eye 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 3/58 (5.2%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Age-related macular degeneration 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 2/67 (3%) 1/58 (1.7%) 0/58 (0%) 0/23 (0%) 1/25 (4%) 1/16 (6.3%)
    Macular scar 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 2/16 (12.5%)
    Choroidal neovascularisation 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 2/67 (3%) 0/58 (0%) 2/58 (3.4%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Eye pruritus 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 1/58 (1.7%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Ocular discomfort 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 2/58 (3.4%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Visual impairment 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 1/58 (1.7%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Infections and infestations
    Urinary tract infection 1/9 (11.1%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 0/58 (0%) 2/58 (3.4%) 1/23 (4.3%) 0/25 (0%) 0/16 (0%)
    Nasopharyngitis 1/9 (11.1%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 4/67 (6%) 2/58 (3.4%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Viral upper respiratory tract infection 0/9 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Influenza 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 1/58 (1.7%) 3/58 (5.2%) 0/23 (0%) 0/25 (0%) 2/16 (12.5%)
    Upper respiratory tract infection 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 1/58 (1.7%) 2/58 (3.4%) 1/23 (4.3%) 0/25 (0%) 1/16 (6.3%)
    Bronchitis 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 2/58 (3.4%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Injury, poisoning and procedural complications
    Laceration 0/9 (0%) 0/6 (0%) 1/6 (16.7%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Contusion 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 4/67 (6%) 2/58 (3.4%) 2/58 (3.4%) 1/23 (4.3%) 0/25 (0%) 0/16 (0%)
    Pain in extremity 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 3/58 (5.2%) 1/58 (1.7%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Nervous system disorders
    Headache 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 1/67 (1.5%) 3/58 (5.2%) 3/58 (5.2%) 1/23 (4.3%) 0/25 (0%) 1/16 (6.3%)
    Respiratory, thoracic and mediastinal disorders
    Respiratory tract congestion 0/9 (0%) 1/6 (16.7%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Cough 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Oropharyngeal pain 0/9 (0%) 0/6 (0%) 1/6 (16.7%) 0/3 (0%) 2/67 (3%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 0/16 (0%)
    Skin and subcutaneous tissue disorders
    Urticaria 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 0/67 (0%) 0/58 (0%) 0/58 (0%) 0/23 (0%) 0/25 (0%) 1/16 (6.3%)
    Vascular disorders
    Hypertension 0/9 (0%) 0/6 (0%) 0/6 (0%) 0/3 (0%) 2/67 (3%) 0/58 (0%) 0/58 (0%) 1/23 (4.3%) 0/25 (0%) 1/16 (6.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Therapeutic Area Head,
    Organization Allergan, Inc
    Phone 714-246-4500
    Email clinicaltrials@allergan.com
    Responsible Party:
    Allergan
    ClinicalTrials.gov Identifier:
    NCT01397409
    Other Study ID Numbers:
    • 150998-001
    • 2011-002526-43
    • REACH Study
    First Posted:
    Jul 19, 2011
    Last Update Posted:
    Apr 16, 2019
    Last Verified:
    Apr 1, 2019