Age-related Macular Degeneration
Conditions
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.
Interventions
DRUGAGN-150998
AGN-150998 Intravitreal injection.
DRUGranibizumab
Ranibizumab 0.5 mg given by intravitreal injection.
OTHERSham Injection
Stage 3: Sham injection at Weeks 12 and 16.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Countries
Australia, Austria, France, Germany, Israel, Italy, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stage 1: AGN-150998 4.2 mg Stage 1: AGN-150998 4.2 mg given as a single intravitreal injection. | 9 |
| Stage 1: AGN-150998 3.0 mg Stage 1: AGN-150998 3.0 mg given as a single intravitreal injection. | 6 |
| Stage 1: AGN-150998 2.0 mg Stage 1: AGN-150998 2.0 mg given as a single intravitreal injection | 6 |
| Stage 1: AGN-150998 1.0 mg Stage 1: AGN-150998 1.0 mg given as a single intravitreal injection. | 3 |
| 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. | 67 |
| 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. | 58 |
| 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. | 58 |
| 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. | 23 |
| 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. | 25 |
| Stage 3: Ranibizumab 0.5 mg Stage 3: ranibizumab 0.5 mg given as intravitreal injections every 4 weeks for 16 weeks | 16 |
| Total | 271 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage 2 | Adverse Event | 0 | 0 | 0 | 0 | 6 | 3 | 0 | 0 | 0 | 0 |
| Stage 2 | Other Miscellaneous Reasons | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Stage 2 | Personal Reasons | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Stage 3 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Stage 3 | Other Miscellaneous Reasons | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 82.3 Years | 75.3 Years | 79.3 Years | 67.7 Years | 80.4 Years | 78.6 Years | 78.5 Years | 77.9 Years | 75.5 Years | 76.5 Years | 77.2 Years |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 4 Participants | 2 Participants | 34 Participants | 35 Participants | 38 Participants | 13 Participants | 18 Participants | 8 Participants | 159 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 2 Participants | 1 Participants | 33 Participants | 23 Participants | 20 Participants | 10 Participants | 7 Participants | 8 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 9 | 5 / 6 | 4 / 6 | 2 / 3 | 51 / 67 | 35 / 58 | 35 / 58 | 10 / 23 | 15 / 25 | 9 / 16 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 | 1 / 6 | 0 / 3 | 11 / 67 | 6 / 58 | 5 / 58 | 0 / 23 | 0 / 25 | 0 / 16 |
Outcome results
Primary
Highest Tolerated Dose (HTD) of AGN-150998
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
Population: Safety population included all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1 All Participants | Highest Tolerated Dose (HTD) of AGN-150998 | 4.2 mg |
Primary
Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye
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
Population: Safety population included all treated participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 All Participants | Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 527.6 microns | Standard Deviation 126.79 |
| Stage 1 All Participants | Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 (n=9,6,6,2) | -185.4 microns | Standard Deviation 161.23 |
| Stage 1: AGN-150998 3.0 mg | Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 (n=9,6,6,2) | -239.5 microns | Standard Deviation 234.03 |
| Stage 1: AGN-150998 3.0 mg | Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 540.3 microns | Standard Deviation 284.34 |
| Stage 1: AGN-150998 2.0 mg | Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 500.3 microns | Standard Deviation 155.65 |
| Stage 1: AGN-150998 2.0 mg | Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 (n=9,6,6,2) | -212.3 microns | Standard Deviation 182.94 |
| Stage 1: AGN-150998 1.0 mg | Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 564.3 microns | Standard Deviation 115.68 |
| Stage 1: AGN-150998 1.0 mg | Stage 1: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 (n=9,6,6,2) | -113.5 microns | Standard Deviation 135.06 |
Primary
Stage 2: Time Between Baseline Treatment and Recurrence of Active Disease
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
Population: Per-protocol Population included all treated participants who received all scheduled treatments.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1 All Participants | Stage 2: Time Between Baseline Treatment and Recurrence of Active Disease | 59.0 days |
| Stage 1: AGN-150998 3.0 mg | Stage 2: Time Between Baseline Treatment and Recurrence of Active Disease | 57.0 days |
| Stage 1: AGN-150998 2.0 mg | Stage 2: Time Between Baseline Treatment and Recurrence of Active Disease | 57.0 days |
Primary
Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
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
Population: Modified-Intent-to-Treat (mITT) Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 All Participants | Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline | 58.5 letters | Standard Deviation 14.29 |
| Stage 1 All Participants | Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Change from Baseline at Week 16 | 8.2 letters | Standard Deviation 7.89 |
| Stage 1: AGN-150998 3.0 mg | Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline | 58.4 letters | Standard Deviation 13.49 |
| Stage 1: AGN-150998 3.0 mg | Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Change from Baseline at Week 16 | 6.3 letters | Standard Deviation 7.81 |
| Stage 1: AGN-150998 2.0 mg | Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline | 60.4 letters | Standard Deviation 16.41 |
| Stage 1: AGN-150998 2.0 mg | Stage 3: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Change from Baseline at Week 16 | 5.3 letters | Standard Deviation 11.08 |
Secondary
Stage 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
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
Population: Per-protocol Population included all treated participants who received all scheduled treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 All Participants | Stage 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline | 54.5 letters | Standard Deviation 13.9 |
| Stage 1 All Participants | Stage 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Change from Baseline at Week 4 (n=62,56,57) | 4.7 letters | Standard Deviation 9.71 |
| Stage 1: AGN-150998 3.0 mg | Stage 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline | 52.7 letters | Standard Deviation 12.62 |
| Stage 1: AGN-150998 3.0 mg | Stage 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Change from Baseline at Week 4 (n=62,56,57) | 8.4 letters | Standard Deviation 11.51 |
| Stage 1: AGN-150998 2.0 mg | Stage 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline | 55.4 letters | Standard Deviation 13 |
| Stage 1: AGN-150998 2.0 mg | Stage 2: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Change from Baseline at Week 4 (n=62,56,57) | 5.9 letters | Standard Deviation 64 |
Secondary
Stage 2: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye
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
Population: Per-protocol Population included all treated participants who received all scheduled treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 All Participants | Stage 2: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 524.6 microns | Standard Deviation 170.71 |
| Stage 1 All Participants | Stage 2: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 (n=61,56,57) | -179.5 microns | Standard Deviation 123.76 |
| Stage 1: AGN-150998 3.0 mg | Stage 2: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 507.3 microns | Standard Deviation 139.88 |
| Stage 1: AGN-150998 3.0 mg | Stage 2: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 (n=61,56,57) | -155.3 microns | Standard Deviation 109.13 |
| Stage 1: AGN-150998 2.0 mg | Stage 2: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 497.1 microns | Standard Deviation 122.04 |
| Stage 1: AGN-150998 2.0 mg | Stage 2: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 (n=61,56,57) | -157.3 microns | Standard Deviation 121.95 |
Secondary
Stage 2: Time Between Second Treatment and Recurrence of Active Disease
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
Population: mITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1 All Participants | Stage 2: Time Between Second Treatment and Recurrence of Active Disease | 85.0 days |
| Stage 1: AGN-150998 3.0 mg | Stage 2: Time Between Second Treatment and Recurrence of Active Disease | 112.0 days |
| Stage 1: AGN-150998 2.0 mg | Stage 2: Time Between Second Treatment and Recurrence of Active Disease | 111.0 days |
Secondary
Stage 3: Change From Baseline in BCVA in the Study Eye
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
Population: Per-protocol Population included all treated participants who received all scheduled treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 All Participants | Stage 3: Change From Baseline in BCVA in the Study Eye | Baseline | 58.5 letters | Standard Deviation 14.29 |
| Stage 1 All Participants | Stage 3: Change From Baseline in BCVA in the Study Eye | Change from Baseline at Week 4 | 5.0 letters | Standard Deviation 7.4 |
| Stage 1: AGN-150998 3.0 mg | Stage 3: Change From Baseline in BCVA in the Study Eye | Baseline | 58.4 letters | Standard Deviation 13.49 |
| Stage 1: AGN-150998 3.0 mg | Stage 3: Change From Baseline in BCVA in the Study Eye | Change from Baseline at Week 4 | 4.6 letters | Standard Deviation 5.98 |
| Stage 1: AGN-150998 2.0 mg | Stage 3: Change From Baseline in BCVA in the Study Eye | Change from Baseline at Week 4 | 3.9 letters | Standard Deviation 6.01 |
| Stage 1: AGN-150998 2.0 mg | Stage 3: Change From Baseline in BCVA in the Study Eye | Baseline | 60.4 letters | Standard Deviation 16.41 |
Secondary
Stage 3: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye
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
Population: Per-protocol Population included all treated participants who received all scheduled treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 All Participants | Stage 3: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 466.0 microns | Standard Deviation 125.96 |
| Stage 1 All Participants | Stage 3: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 | -119.8 microns | Standard Deviation 68.5 |
| Stage 1: AGN-150998 3.0 mg | Stage 3: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 526.1 microns | Standard Deviation 165.09 |
| Stage 1: AGN-150998 3.0 mg | Stage 3: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 | -168.3 microns | Standard Deviation 137.07 |
| Stage 1: AGN-150998 2.0 mg | Stage 3: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Baseline | 463.3 microns | Standard Deviation 94.56 |
| Stage 1: AGN-150998 2.0 mg | Stage 3: Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Change from Baseline at Week 4 | -98.4 microns | Standard Deviation 65.22 |