Geographic Atrophy, Dry Age-Related Macular Degeneration
Conditions
Keywords
Geographic Atrophy (GA), Dry age-related macular degeneration, AMD, Zimura (previous name), Anti-inflammatory, complement factor C5 inhibitor, ARC1905, avacincaptad pegol
Brief summary
The objectives of this study were to evaluate the safety and efficacy of Zimura intravitreal (IVT) administration when administered in participants with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD).
Detailed description
Participants will receive monthly intravitreal injections of Zimura or Sham for 18 months.
Interventions
Avacincaptad Pegol 20 mg/mL solution for intravitreal (IVT) injection
OTHERSham
The Sham procedure included the blunt opening of an empty, needleless syringe barrel placed on the conjunctiva in the inferotemporal quadrant of the eyeball to simulate the pressure of an injection.
Sponsors
IVERIC bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The Reading Center team and Sponsor were also masked.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants of either gender aged ≥ 50 years * Diagnosis of Non-foveal GA secondary to dry AMD
Exclusion criteria
* Evidence of Choroidal Neovascularization (CNV) * GA secondary to any condition other than AMD * Any prior treatment for AMD or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins and minerals * Any intraocular surgery or thermal laser within three (3) months of trial entry * Any prior thermal laser in the macular region, regardless of indication * Any ocular or periocular infection in the twelve (12) weeks * Previous therapeutic radiation in the region of the study eye * Any sign of diabetic retinopathy in either eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Geographic Atrophy as Measured by Fundus Autofluorescence | Baseline and 12 months | The least squares mean change in geographic atrophy (GA) from baseline to Month 12 was measured by fundus autofluorescence (FAF). The square root of the GA area was used in the analysis. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for this primary endpoint; the Zimura 1 mg group was for descriptive purposes only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Best Corrected Visual Acuity Using Early Treatment Diabetic Retinopathy Study Letters | Baseline and 12 months | The least squares mean change in best-corrected visual acuity (BCVA) from baseline to Month 12 was measured using early treatment diabetic retinopathy study \[ETDRS\] letters. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for the secondary endpoints; the Zimura 1 mg group was for descriptive purposes only. |
| Change From Baseline in Low Luminance BCVA Using Early Treatment Diabetic Retinopathy Study Letters | Baseline and 12 months | The least squares mean change in low luminance (LL) BCVA from baseline to Month 12 was measured using ETDRS letters. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for the secondary endpoints; the Zimura 1 mg group was for descriptive purposes only. |
Countries
Croatia, Czechia, Estonia, Hungary, Israel, Latvia, United States
Participant flow
Pre-assignment details
Study participants are planned to receive 18 monthly intravitreal injections of Zimura and/or Sham in a single designated study eye. The study eye is designated by the Investigator prior to first administration of study drug and does not change throughout the duration of study participation.
Participants by arm
| Arm | Count |
|---|---|
| Zimura 1 mg [Part 1] Participants received 1 mg of Zimura in the study eye administered via intravitreal (IVT) injection on Day 1 and monthly up to 18 months. | 26 |
| Zimura 2 mg [Part 1] Participants received 2 mg of Zimura in the study eye administered via IVT injection on Day 1 and monthly up to 18 months. | 25 |
| Sham [Part 1] Participants received a Sham injection of an empty, needleless syringe administered in the study eye on Day 1 and monthly up to 18 months. | 26 |
| Zimura 2 mg (Zimura 2mg+Sham) [Part 2] Participants received 2 mg of Zimura in the study eye administered via IVT injection and a Sham administration on Day 1 and monthly up to 18 months. | 42 |
| Zimura 4 mg (Zimura 2mg+Zimura 2mg) [Part 2] Participants received 4 mg of Zimura in the study eye administered via 2 IVT injections on Day 1 and monthly up to 18 months. | 83 |
| Sham (Sham+Sham) [Part 2] Participants received 2 Sham injections of empty, needleless syringes administered in the study eye on Day 1 and monthly up to 18 months. | 84 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 | 2 | 1 |
| Overall Study | Concern over coronavirus disease care | 0 | 0 | 0 | 0 | 2 | 1 |
| Overall Study | Death | 1 | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Investigator decision | 0 | 0 | 0 | 1 | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 0 | 0 | 1 |
| Overall Study | Participant non-compliance | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Placed in hospice care | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Sponsor decision | 1 | 2 | 1 | 5 | 13 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 4 | 4 | 17 | 8 |
Baseline characteristics
| Characteristic | Zimura 1 mg [Part 1] | Zimura 2 mg [Part 1] | Sham [Part 1] | Zimura 2 mg (Zimura 2mg+Sham) [Part 2] | Zimura 4 mg (Zimura 2mg+Zimura 2mg) [Part 2] | Sham (Sham+Sham) [Part 2] | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 21 Participants | 24 Participants | 36 Participants | 78 Participants | 80 Participants | 262 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 4 Participants | 2 Participants | 6 Participants | 5 Participants | 4 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 24 Participants | 25 Participants | 42 Participants | 82 Participants | 83 Participants | 281 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 25 Participants | 25 Participants | 25 Participants | 42 Participants | 82 Participants | 82 Participants | 281 Participants |
| Sex: Female, Male Female | 15 Participants | 18 Participants | 18 Participants | 27 Participants | 58 Participants | 61 Participants | 197 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 8 Participants | 15 Participants | 25 Participants | 23 Participants | 89 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 26 | 0 / 25 | 0 / 26 | 1 / 42 | 1 / 83 | 1 / 84 | 3 / 176 | 1 / 110 |
| other Total, other adverse events | 13 / 26 | 13 / 25 | 10 / 26 | 34 / 42 | 66 / 83 | 49 / 84 | 126 / 176 | 59 / 110 |
| serious Total, serious adverse events | 3 / 26 | 4 / 25 | 7 / 26 | 8 / 42 | 21 / 83 | 21 / 84 | 36 / 176 | 28 / 110 |
Outcome results
Primary
Change From Baseline in Geographic Atrophy as Measured by Fundus Autofluorescence
The least squares mean change in geographic atrophy (GA) from baseline to Month 12 was measured by fundus autofluorescence (FAF). The square root of the GA area was used in the analysis. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for this primary endpoint; the Zimura 1 mg group was for descriptive purposes only.
Time frame: Baseline and 12 months
Population: This study was conducted in 2 Parts. The analyses were based on comparisons of Zimura 2mg vs. Sham control and Zimura 4mg vs. Sham control. For comparison of Zimura 2mg vs. Sham control, participants randomized in Part 1 were combined with participants randomized in Part 2. Comparison of Zimura 4mg vs. Sham control was based on participants randomized in Part 2 only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zimura 2 mg [Part 1 & Part 2 Combined] | Change From Baseline in Geographic Atrophy as Measured by Fundus Autofluorescence | 0.292 millimeters (mm) | Standard Error 0.077 |
| Sham [Part 1 & Part 2 Combined] | Change From Baseline in Geographic Atrophy as Measured by Fundus Autofluorescence | 0.402 millimeters (mm) | Standard Error 0.075 |
| Zimura 4 mg [Part 2] | Change From Baseline in Geographic Atrophy as Measured by Fundus Autofluorescence | 0.321 millimeters (mm) | Standard Error 0.074 |
| Sham [Part 2] | Change From Baseline in Geographic Atrophy as Measured by Fundus Autofluorescence | 0.444 millimeters (mm) | Standard Error 0.072 |
Comparison: Difference in least squares means between groups calculated as (Sham) minus (Zimura).p-value: 0.0072Model for repeated measures (MRM)
Comparison: Difference in least squares means between groups calculated as (Sham) minus (Zimura).p-value: 0.0051Model for repeated measures (MRM)
Secondary
Change From Baseline in Best Corrected Visual Acuity Using Early Treatment Diabetic Retinopathy Study Letters
The least squares mean change in best-corrected visual acuity (BCVA) from baseline to Month 12 was measured using early treatment diabetic retinopathy study \[ETDRS\] letters. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for the secondary endpoints; the Zimura 1 mg group was for descriptive purposes only.
Time frame: Baseline and 12 months
Population: This study was conducted in 2 Parts. The analyses were based on comparisons of Zimura 2mg vs. Sham control and Zimura 4mg vs. Sham control. For comparison of Zimura 2mg vs. Sham control, participants randomized in Part 1 were combined with participants randomized in Part 2. Comparison of Zimura 4mg vs. Sham control was based on participants randomized in Part 2 only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zimura 2 mg [Part 1 & Part 2 Combined] | Change From Baseline in Best Corrected Visual Acuity Using Early Treatment Diabetic Retinopathy Study Letters | -7.90 ETDRS Letters | Standard Error 2.66 |
| Sham [Part 1 & Part 2 Combined] | Change From Baseline in Best Corrected Visual Acuity Using Early Treatment Diabetic Retinopathy Study Letters | -9.29 ETDRS Letters | Standard Error 2.59 |
| Zimura 4 mg [Part 2] | Change From Baseline in Best Corrected Visual Acuity Using Early Treatment Diabetic Retinopathy Study Letters | -3.79 ETDRS Letters | Standard Error 3.11 |
| Sham [Part 2] | Change From Baseline in Best Corrected Visual Acuity Using Early Treatment Diabetic Retinopathy Study Letters | -3.51 ETDRS Letters | Standard Error 2.99 |
Comparison: Difference in least squares mean between groups calculated as (Zimura) minus (Sham).p-value: 0.3464Model for repeated measures (MRM)
Comparison: Difference in least squares mean between groups calculated as (Zimura) minus (Sham).p-value: 0.883Model for repeated measures (MRM)
Secondary
Change From Baseline in Low Luminance BCVA Using Early Treatment Diabetic Retinopathy Study Letters
The least squares mean change in low luminance (LL) BCVA from baseline to Month 12 was measured using ETDRS letters. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for the secondary endpoints; the Zimura 1 mg group was for descriptive purposes only.
Time frame: Baseline and 12 months
Population: This study was conducted in 2 Parts. The analyses were based on comparisons of Zimura 2mg vs. Sham control and Zimura 4mg vs. Sham control. For comparison of Zimura 2mg vs. Sham control, participants randomized in Part 1 were combined with participants randomized in Part 2. Comparison of Zimura 4mg vs. Sham control was based on participants randomized in Part 2 only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Zimura 2 mg [Part 1 & Part 2 Combined] | Change From Baseline in Low Luminance BCVA Using Early Treatment Diabetic Retinopathy Study Letters | -1.03 ETDRS Letters | Standard Error 3.4 |
| Sham [Part 1 & Part 2 Combined] | Change From Baseline in Low Luminance BCVA Using Early Treatment Diabetic Retinopathy Study Letters | -1.41 ETDRS Letters | Standard Error 3.3 |
| Zimura 4 mg [Part 2] | Change From Baseline in Low Luminance BCVA Using Early Treatment Diabetic Retinopathy Study Letters | 1.53 ETDRS Letters | Standard Error 3.53 |
| Sham [Part 2] | Change From Baseline in Low Luminance BCVA Using Early Treatment Diabetic Retinopathy Study Letters | 2.97 ETDRS Letters | Standard Error 3.39 |
Comparison: Difference in least squares mean between groups calculated as (Zimura) minus (Sham).p-value: 0.8405Model for repeated measures (MRM)
Comparison: Difference in least squares mean between groups calculated as (Zimura) minus (Sham).p-value: 0.5017Model for repeated measures (MRM)