Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to demonstrate a treatment effect of ESBA1008 applied as a microvolume injection or infusion on retinal function and morphology in subjects with exudative age-related macular degeneration (AMD).
This 4-cohort study was conducted in 2 stages. Stage 1 consisted out of 2 Cohorts. In each cohort subjects were randomized 10:3 to either receive ESBA1008 (Cohort 1 : 2 injections, Cohort 2 : 1 infusion and 1 injection) or 2 Lucentis injections. Stage 2 was conducted similarly with a different dosing level for ESBA1008 (Cohort 3 and 4). Subjects had follow-up visits at Day 7 and Day 14. All cohorts receiving ESBA1008 on Day 0 also received ESBA1008 6mg/50 μL via injection on Day 28. After the Day 28 visit (all cohorts), subjects returned for follow up visits at Day 42 and Day 56.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ESBA1008 1.2 mg/10 μL | Experimental | Cohort 1: One intravitreal injection on Day 0, followed by one intravitreal (IVT) injection of ESBA1008 6 mg/50 μL on Day 28 |
|
| ESBA1008 1 mg/8.3 μL | Experimental | Cohort 2: One intravitreal infusion on Day 0, followed by one intravitreal injection of ESBA1008 6 mg/50 μL on Day 28 |
|
| ESBA1008 0.6 mg/10 μL | Experimental | Cohort 3: One intravitreal injection on Day 0, followed by one intravitreal injection of ESBA1008 6 mg/50 μL on Day 28 |
|
| ESBA1008 0.5 mg/8.3 μL | Experimental | Cohort 4: One intravitreal infusion on Day 0, followed by one intravitreal injection of ESBA1008 6 mg/50 μL on Day 28 |
|
| Ranibizumab 0.5 mg in 50 μL | Active Comparator | Cohorts 1-4: One intravitreal injection on Day 0, followed by another intravitreal injection on Day 28 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ESBA1008 solution | Drug | Intravitreal injection or infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28 | A subject was considered a responder if at least 3 out of the following 4 criteria were fulfilled in comparison to baseline:
| Baseline, Day 14, Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in BCVA, Cohort 1 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Clinical Project Group Leader, GCRA, Pharma | Alcon Research | Study Director |
Not provided
Of the 107 enrolled, 55 subjects were exited as screen failures prior to randomization. This reporting group includes all randomized participants (52).
Subjects were recruited from 12 investigational centers located in the US, Australia, and the Dominican Republic.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 - ESBA | ESBA1008 solution Day 0 (1.2 mg) and Day 28 (6 mg) |
| FG001 | Cohort 1 - Ranibizumab | Ranibizumab 0.5 mg injection, Day 0 and Day 28 |
| FG002 | Cohort 2 - ESBA | ESBA1008 solution Day 0 (1 mg) and Day 28 (6 mg) |
| FG003 | Cohort 2 - Ranibizumab | Ranibizumab 0.5 mg injection, Day 0 and Day 28 |
| FG004 | Cohort 3 - ESBA | ESBA1008 solution Day 0 (0.6 mg) and Day 28 (6 mg) |
| FG005 | Cohort 3 - Ranibizumab | Ranibizumab 0.5 mg injection, Day 0 and Day 28 |
| FG006 | Cohort 4 - ESBA | ESBA1008 solution Day 0 (0.5 mg) and Day 28 (6 mg) |
| FG007 | Cohort 4 - Ranibizumab | Ranibizumab 0.5 mg injection, Day 0 and Day 28 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables (BCVA and/or CSFT). Here, "n" is the number of subjects in each cohort for each arm group, respectively.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | ESBA | All subjects who were treated with ESBA1008. |
| BG001 | LUCENTIS | All subjects who were treated with LUCENTIS. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28 | A subject was considered a responder if at least 3 out of the following 4 criteria were fulfilled in comparison to baseline:
| This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables (BCVA and/or CSFT). Here, "n" is the number of subjects in each arm group. | Posted | Number | 90% Confidence Interval | percentage of responders | Baseline, Day 14, Day 28 |
|
Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to visit Day 56). Ocular adverse events are presented for both study eye and non-study eye. AEs were reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject administered study drug. AEs were obtained as solicited comments from subjects and as observations by the Investigator as outlined in the protocol.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stage 1 ESBA 1.2 mg INJ | All subjects treated with ESBA1008 1.2 mg via injection |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pubis fracture | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Androgen deficiency | Endocrine disorders | MedDRA (16.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Project Group Leader, GCRA, Pharma | Alcon Research, Ltd. | 1-888-451-3937 | alcon.medinfo@alcon.com |
| ID | Term |
|---|---|
| D020256 | Choroidal Neovascularization |
| ID | Term |
|---|---|
| D015862 | Choroid Diseases |
| D014603 | Uveal Diseases |
| D005128 | Eye Diseases |
| D009389 | Neovascularization, Pathologic |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069579 | Ranibizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Ranibizumab | Drug | Intravitreal injection |
|
|
| Change From Baseline in BCVA, Cohort 2 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
| Change From Baseline in BCVA, Cohort 3 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
| Change From Baseline in BCVA, Cohort 4 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
| Change From Baseline in CSFT, Cohort 1 | CSFT was assessed by Spectral-Domain Optical Coherence Tomography (SD-OCT) and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
| Change From Baseline in CSFT, Cohort 2 | CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
| Change From Baseline in CSFT, Cohort 3 | CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
| Change From Baseline in CSFT, Cohort 4 | CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Number | participants |
|
| Best corrected visual acuity (BCVA) | BCVA (with spectacles or other visual corrective devices) using Early Treatment Diabetic Retinopathy Study (ETDRS) testing was reported in letters read correctly out of 70 letters on the chart. | Mean | Standard Deviation | letters |
|
| Central subfield thickness (CSFT) | Mean | Standard Deviation | microns |
|
| Cohort 1 |
ESBA1008 solution Day 0 (1.2 mg) and Day 28 (6 mg), or Ranibizumab Day 0 and Day 28, based on randomization |
| OG001 | Cohort 2 | ESBA1008 solution Day 0 (1 mg) and Day 28 (6 mg), or Ranibizumab Day 0 and Day 28, based on randomization |
| OG002 | Cohort 3 | ESBA1008 solution Day 0 (0.6 mg) and Day 28 (6 mg), or Ranibizumab Day 0 and Day 28, based on randomization |
| OG003 | Cohort 4 | ESBA1008 solution Day 0 (0.5 mg) and Day 28 (6 mg), or Ranibizumab Day 0 and Day 28, based on randomization |
|
|
| Secondary | Change From Baseline in BCVA, Cohort 1 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. | This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables, with last observation carried forward (LOCF) imputation for missing values. | Posted | Mean | Standard Deviation | letters | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
|
|
|
| Secondary | Change From Baseline in BCVA, Cohort 2 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. | This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables, with LOCF imputation for missing values. | Posted | Mean | Standard Deviation | letters | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
|
|
|
| Secondary | Change From Baseline in BCVA, Cohort 3 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. | This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables, with LOCF imputation for missing values. | Posted | Mean | Standard Deviation | letters | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
|
|
|
| Secondary | Change From Baseline in BCVA, Cohort 4 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. | This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables, with LOCF imputation for missing values. | Posted | Mean | Standard Deviation | letters | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
|
|
|
| Secondary | Change From Baseline in CSFT, Cohort 1 | CSFT was assessed by Spectral-Domain Optical Coherence Tomography (SD-OCT) and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables, with LOCF imputation for missing values. | Posted | Mean | Standard Deviation | microns | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
|
|
|
| Secondary | Change From Baseline in CSFT, Cohort 2 | CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables, with LOCF imputation for missing values. | Posted | Mean | Standard Deviation | microns | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
|
|
|
| Secondary | Change From Baseline in CSFT, Cohort 3 | CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables, with LOCF imputation for missing values. | Posted | Mean | Standard Deviation | microns | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
|
|
|
| Secondary | Change From Baseline in CSFT, Cohort 4 | CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables, with LOCF imputation for missing values. | Posted | Mean | Standard Deviation | microns | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 |
|
|
|
| 0 |
| 10 |
| 6 |
| 10 |
| EG001 | Stage 1 ESBA 1 mg INF | All subjects treated with ESBA1008 1 mg via infusion | 0 | 10 | 4 | 10 |
| EG002 | Stage 1 LUCENTIS 0.5 mg INJ | All subjects treated with LUCENTIS via injection in Stage 1 | 1 | 6 | 6 | 6 |
| EG003 | Stage 2 ESBA 0.6 mg INJ | All subjects treated with ESBA1008 0.6 mg via injection | 1 | 10 | 6 | 10 |
| EG004 | Stage 2 ESBA 0.5 mg INF | All subjects treated with ESBA1008 0.5 mg via infusion | 0 | 10 | 7 | 10 |
| EG005 | Stage 2 LUCENTIS 0.5 mg INJ | All subjects treated with LUCENTIS via injection in Stage 2 | 0 | 6 | 4 | 6 |
| EG006 | Pretreatment | All subjects who consented to participate in the study prior to the initiation of study treatment | 1 | 107 | 3 | 107 |
| Fall | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abnormal sensation in eye | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Chalazion | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Choroidal neovascularisation | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Conjunctival hyperaemia | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Conjunctival oedema | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Corneal epithelium defect | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Eyelid pain | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Eyelids pruritus | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Foreign body sensation in eyes | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Metamorphopsia | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Ocular discomfort | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Retinal haemorrhage | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Retinal pigment epitheliopathy | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Xanthopsia | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Keratitis bacterial | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Traumatic haemorrhage | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Biopsy ear | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA (16.0) | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
| D008679 |
| Metaplasia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Day 28 |
|
| Day 42 |
|
| Day 56 |
|
| Day 28 |
|
| Day 42 |
|
| Day 56 |
|
| Day 28 |
|
| Day 42 |
|
| Day 56 |
|
| Day 28 |
|
| Day 42 |
|
| Day 56 |
|
| Day 28 |
|
| Day 42 |
|
| Day 56 |
|
| Day 28 |
|
| Day 42 |
|
| Day 56 |
|
| Day 28 |
|
| Day 42 |
|
| Day 56 |
|
| Day 28 |
|
| Day 42 |
|
| Day 56 |
|