Neovascular Age-related Macular Degeneration
Conditions
Keywords
Zimura (previous name), ARC1905, Lucentis, ranibizumab, Wet AMD, avacincaptad pegol, complement factor C5 inhibitor
Brief summary
To assess the safety of intravitreal Zimura™ (complement factor C5 inhibitor) administered in combination with Lucentis® 0.5 mg in treatment naïve subjects with neovascular age related macular degeneration (NVAMD)
Interventions
Avacincaptad Pegol in combination with Lucentis
DRUGLucentis
Avacincaptad Pegol in combination with Lucentis
Sponsors
Ophthotech Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Active subfoveal NVAMD
Exclusion criteria
* History or evidence of severe cardiac disease * Any major surgical procedure within one month of trial entry * Subjects with a clinically significant laboratory value * Any treatment with an investigational agent in the past 60 days for any condition * Women who are pregnant or nursing * Known serious allergies to the fluorescein dye used in angiography, povidone iodine, to the components of the ranibizumab formulation, or to the components of the Zimura formulation * Any prior treatment for AMD other than oral supplements of vitamins and minerals
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Adverse Events | 6 months | Number of Participants with systemic treatment-emergent Adverse Events (with calculated percentage) |
| Ophthalmic Adverse Events | 6 months | Number of participants with ophthalmic Adverse Events (with calculated percentage) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline - ECG | 6 months | Number of patients with a change on their Month 6 ECG when compared to their baseline ECG |
| Mean Change From Baseline - Study Eye ETDRS Visual Acuity | 6 months | Mean change from Baseline to Month 6 in the number of letters read by the study eye using the ETDRS Visual Acuity charts. Higher ETDRS letters represents better vision and a larger change in ETDRS letters represents better functioning. |
| Mean Change From Baseline - Vital Signs | 6 months | Mean change from Baseline to Month 6 in blood pressure (mm Hg). A negative number indicates a decrease and a positive number indicates an increase. |
Countries
Hungary, Latvia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Monthly administration of Lucentis 0.5 mg followed 2 days later by Zimura 4mg | 10 |
| Cohort 2 Monthly administration of Zimura 2mg + Lucentis 0.5 mg (given on the same day) | 10 |
| Cohort 3 Zimura 2mg + Lucentis 0.5 mg Induction Phase (Day 1 - Month 2): Monthly administration of Zimura 2mg + Lucentis 0.5 mg given on the same day followed 14 days later with Zimura 2mg (Total: 6 doses of Zimura & 3 doses of Lucentis) Maintenance Phase (Month 3-5): Monthly administration of Zimura 2mg + Lucentis 0.5mg given on the same day (Total: 3 doses of Zimura and 3 doses of Lucentis) | 22 |
| Cohort 4 Zimura 2mg + Lucentis 0.5 mg Induction Phase (Day 1 - Month 2): Monthly administration of Zimura 2mg + Lucentis 0.5 mg given on the same day followed 14 days later with Zimura 2mg (6 doses of Zimura and 3 doses of Lucentis) Maintenance Phase (Month 3-5): Monthly administration of Zimura 2mg followed 2 days later by Lucentis 0.5mg + Zimura 2mg (6 doses of Zimura and 3 doses of Lucentis) | 22 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 2 | Cohort 3 | Cohort 1 | Cohort 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 20 Participants | 8 Participants | 21 Participants | 59 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Age, Continuous | 77.9 years STANDARD_DEVIATION 6.62 | 74.1 years STANDARD_DEVIATION 7.41 | 73.7 years STANDARD_DEVIATION 11.27 | 78.1 years STANDARD_DEVIATION 7.4 | 76.0 years STANDARD_DEVIATION 8.07 |
| ETDRS Visual Acuity -Study Eye | 51.5 number of letters read STANDARD_DEVIATION 5.4 | 52.5 number of letters read STANDARD_DEVIATION 9.4 | 53.9 number of letters read STANDARD_DEVIATION 9 | 53.2 number of letters read STANDARD_DEVIATION 9.9 | 52.8 number of letters read STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 21 Participants | 10 Participants | 21 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 22 Participants | 10 Participants | 22 Participants | 64 Participants |
| Region of Enrollment Hungary | 3 participants | 8 participants | 0 participants | 2 participants | 13 participants |
| Region of Enrollment Latvia | 1 participants | 2 participants | 0 participants | 3 participants | 6 participants |
| Region of Enrollment United States | 6 participants | 12 participants | 10 participants | 17 participants | 45 participants |
| Sex: Female, Male Female | 8 Participants | 14 Participants | 4 Participants | 12 Participants | 38 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 6 Participants | 10 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 10 / 10 | 7 / 10 | 10 / 22 | 13 / 22 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 | 0 / 22 | 2 / 22 |
Outcome results
Primary
Ophthalmic Adverse Events
Number of participants with ophthalmic Adverse Events (with calculated percentage)
Time frame: 6 months
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Ophthalmic Adverse Events | Participants with all causality events in the fellow eye | 1 Participants |
| Cohort 1 | Ophthalmic Adverse Events | Participants with all causality events in the study eye | 8 Participants |
| Cohort 1 | Ophthalmic Adverse Events | Participants with event related to injection procedure in the study eye | 8 Participants |
| Cohort 1 | Ophthalmic Adverse Events | Participants with event related to injection procedure in the fellow eye | 0 Participants |
| Cohort 1 | Ophthalmic Adverse Events | Participants with event related to study drugs in the study eye | 0 Participants |
| Cohort 1 | Ophthalmic Adverse Events | Participants with event related to study drugs in the fellow eye | 0 Participants |
| Cohort 2 | Ophthalmic Adverse Events | Participants with event related to study drugs in the fellow eye | 0 Participants |
| Cohort 2 | Ophthalmic Adverse Events | Participants with event related to injection procedure in the fellow eye | 0 Participants |
| Cohort 2 | Ophthalmic Adverse Events | Participants with all causality events in the fellow eye | 1 Participants |
| Cohort 2 | Ophthalmic Adverse Events | Participants with event related to injection procedure in the study eye | 4 Participants |
| Cohort 2 | Ophthalmic Adverse Events | Participants with all causality events in the study eye | 4 Participants |
| Cohort 2 | Ophthalmic Adverse Events | Participants with event related to study drugs in the study eye | 0 Participants |
| Cohort 3 | Ophthalmic Adverse Events | Participants with all causality events in the study eye | 11 Participants |
| Cohort 3 | Ophthalmic Adverse Events | Participants with event related to injection procedure in the study eye | 10 Participants |
| Cohort 3 | Ophthalmic Adverse Events | Participants with event related to injection procedure in the fellow eye | 0 Participants |
| Cohort 3 | Ophthalmic Adverse Events | Participants with event related to study drugs in the fellow eye | 0 Participants |
| Cohort 3 | Ophthalmic Adverse Events | Participants with event related to study drugs in the study eye | 0 Participants |
| Cohort 3 | Ophthalmic Adverse Events | Participants with all causality events in the fellow eye | 0 Participants |
| Cohort 4 | Ophthalmic Adverse Events | Participants with event related to study drugs in the study eye | 0 Participants |
| Cohort 4 | Ophthalmic Adverse Events | Participants with event related to study drugs in the fellow eye | 0 Participants |
| Cohort 4 | Ophthalmic Adverse Events | Participants with all causality events in the study eye | 15 Participants |
| Cohort 4 | Ophthalmic Adverse Events | Participants with event related to injection procedure in the fellow eye | 0 Participants |
| Cohort 4 | Ophthalmic Adverse Events | Participants with all causality events in the fellow eye | 2 Participants |
| Cohort 4 | Ophthalmic Adverse Events | Participants with event related to injection procedure in the study eye | 12 Participants |
Primary
Systemic Adverse Events
Number of Participants with systemic treatment-emergent Adverse Events (with calculated percentage)
Time frame: 6 months
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Systemic Adverse Events | All causalities | 6 Participants |
| Cohort 1 | Systemic Adverse Events | Related to study drugs | 0 Participants |
| Cohort 2 | Systemic Adverse Events | Related to study drugs | 0 Participants |
| Cohort 2 | Systemic Adverse Events | All causalities | 5 Participants |
| Cohort 3 | Systemic Adverse Events | All causalities | 5 Participants |
| Cohort 3 | Systemic Adverse Events | Related to study drugs | 0 Participants |
| Cohort 4 | Systemic Adverse Events | All causalities | 11 Participants |
| Cohort 4 | Systemic Adverse Events | Related to study drugs | 0 Participants |
Other Pre-specified
Change From Baseline - ECG
Number of patients with a change on their Month 6 ECG when compared to their baseline ECG
Time frame: 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Change From Baseline - ECG | Clinically Significant Change | 0 Participants |
| Cohort 1 | Change From Baseline - ECG | Not Clinically Signigicant Change | 3 Participants |
| Cohort 1 | Change From Baseline - ECG | No Change | 7 Participants |
| Cohort 1 | Change From Baseline - ECG | Missing | 0 Participants |
| Cohort 2 | Change From Baseline - ECG | Not Clinically Signigicant Change | 5 Participants |
| Cohort 2 | Change From Baseline - ECG | No Change | 5 Participants |
| Cohort 2 | Change From Baseline - ECG | Clinically Significant Change | 0 Participants |
| Cohort 2 | Change From Baseline - ECG | Missing | 0 Participants |
| Cohort 3 | Change From Baseline - ECG | No Change | 18 Participants |
| Cohort 3 | Change From Baseline - ECG | Clinically Significant Change | 0 Participants |
| Cohort 3 | Change From Baseline - ECG | Not Clinically Signigicant Change | 3 Participants |
| Cohort 3 | Change From Baseline - ECG | Missing | 1 Participants |
| Cohort 4 | Change From Baseline - ECG | Not Clinically Signigicant Change | 6 Participants |
| Cohort 4 | Change From Baseline - ECG | Clinically Significant Change | 1 Participants |
| Cohort 4 | Change From Baseline - ECG | Missing | 3 Participants |
| Cohort 4 | Change From Baseline - ECG | No Change | 12 Participants |
Other Pre-specified
Mean Change From Baseline - Study Eye ETDRS Visual Acuity
Mean change from Baseline to Month 6 in the number of letters read by the study eye using the ETDRS Visual Acuity charts. Higher ETDRS letters represents better vision and a larger change in ETDRS letters represents better functioning.
Time frame: 6 months
Population: safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Change From Baseline - Study Eye ETDRS Visual Acuity | 9.0 number of letters read | Standard Deviation 11 |
| Cohort 2 | Mean Change From Baseline - Study Eye ETDRS Visual Acuity | 10.2 number of letters read | Standard Deviation 18.7 |
| Cohort 3 | Mean Change From Baseline - Study Eye ETDRS Visual Acuity | 10.7 number of letters read | Standard Deviation 10.3 |
| Cohort 4 | Mean Change From Baseline - Study Eye ETDRS Visual Acuity | 9.9 number of letters read | Standard Deviation 8.2 |
Other Pre-specified
Mean Change From Baseline - Vital Signs
Mean change from Baseline to Month 6 in blood pressure (mm Hg). A negative number indicates a decrease and a positive number indicates an increase.
Time frame: 6 months
Population: safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Mean Change From Baseline - Vital Signs | Diastolic blood pressure (mm Hg) | -3.2 mm Hg | Standard Deviation 7.93 |
| Cohort 1 | Mean Change From Baseline - Vital Signs | Systolic blood pressure (mm Hg) | -12.0 mm Hg | Standard Deviation 15.04 |
| Cohort 2 | Mean Change From Baseline - Vital Signs | Systolic blood pressure (mm Hg) | 0.7 mm Hg | Standard Deviation 8.92 |
| Cohort 2 | Mean Change From Baseline - Vital Signs | Diastolic blood pressure (mm Hg) | -7.9 mm Hg | Standard Deviation 12.32 |
| Cohort 3 | Mean Change From Baseline - Vital Signs | Systolic blood pressure (mm Hg) | -1.9 mm Hg | Standard Deviation 14.92 |
| Cohort 3 | Mean Change From Baseline - Vital Signs | Diastolic blood pressure (mm Hg) | -4.7 mm Hg | Standard Deviation 11.83 |
| Cohort 4 | Mean Change From Baseline - Vital Signs | Diastolic blood pressure (mm Hg) | -0.4 mm Hg | Standard Deviation 8.24 |
| Cohort 4 | Mean Change From Baseline - Vital Signs | Systolic blood pressure (mm Hg) | -5.8 mm Hg | Standard Deviation 18.24 |