Diabetic Retinopathy
Conditions
Brief summary
This study is open to adults with diabetic macular ischemia who have received laser treatment. The main purpose of this study is to find out whether people with diabetic macular ischemia can tolerate a medicine called BI 765128. In this study, BI 765128 is given to people for the first time. The study has 2 parts. Part A tests 3 doses of BI 765128. Participants get either a low, medium or high dose of BI 765128 as a single injection into the eye. If participants tolerate it well, the highest dose will be used in part B. In part B, participants are put into 2 groups randomly, which means by chance. 1 group gets BI 765128 as injection into the eye. The other group gets sham injections. A sham injection means that it is not a real injection and contains no medicine. Participants cannot tell whether they get the real injection or a sham injection. In this part, participants receive study treatment once every month for 3 months. Participants in part A are in the study for about 4 months and visit the study site about 8 times. Participants in part B are in the study for about 5 months and visit the study site about 7 times. The doctors regularly check participants' health and take note of any unwanted effects.
Interventions
DRUGBI 765128
BI 765128
OTHERSham comparator
Sham comparator
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Description to masking: In Part A no masking will be performed. In Part B participant and investigator will be masked. Description to randomisation: In Part A no randomisation will be performed. In Part B randomisation will be performed.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part A * Panretinal photocoagulation-treated diabetic retinopathy (DR) patients with either no or inactive retinal neovascularization per investigator judgement in the study eye * Male or female subjects of age ≥ 18 years * Evidence of diabetic macular ischemia (DMI) per investigator´s judgement, defined as any degree of disruption of retinal vascularity in optical coherent tomography angiography (OCTA) * Glycosylated Hemoglobin, Type A1C (HbA1c) of ≤ 12.0% * Best-corrected visual acuity (VA) ≤75 letters (20/32) in the study eye * Best corrected visual acuity (VA) in the non-study eye must be equal to or better than best corrected VA in the study eye. If both eyes are eligible and have identical best corrected VA the investigator may select the study eye. * Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use two methods of contraception with at least one of them being a highly effective method of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. * Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial Part B: * Panretinal photocoagulation-treated diabetic retinopathy (DR) patients with either no or inactive retinal neovascularization per investigator judgement * Male or female subjects of age ≥ 18 years * Presence of significant diabetic macular ischemia (DMI): Large foveal avascular zone (FAZ) defined as those with ≥0.5mm2 area present on optical coherent tomography angiography (OCTA). If FAZ is \<0.5mm2 then an enlarged peri-foveal inter-capillary space in at least 1 quadrant will be sufficient. * Glycosylated Hemoglobin, Type A1C (HbA1c) of ≤ 12.0% * Best-corrected visual acuity (VA) ≤85 letters (20/20) in the study eye * If both eyes are eligible, the investigator may select either eye to be the study eye. * Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use two methods of contraception with at least one of them being a highly effective method of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. * Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
Exclusion criteria
Part A: * Subjects receiving intravitreal (IVT) injections for active Diabetic Macular Edema (DME) (anti-vascular endothelial growth factor (VEGF), steroids) and macular laser in the previous 3 months to screening in the study eye * Subjects receiving anti-VEGF IVT injections for active diabetic retinopathy (DR) in the previous 3 months to screening in the study eye * Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol) * Additional progressive eye disease in the study eye that could compromise best corrected visual acuity (VA) (best corrected visual acuity (BCVA)), uncontrolled glaucoma (intra-ocular pressure (IOP)\>24), history of high myopia \> 8 diopters in the study eye. Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation with spectral domain optical coherence tomography (SD-OCT) and optical coherent tomography angiography (OCTA). * Any intraocular surgery in the study eye within 3 months prior to screening * Glaucoma tube shunts * Aphakia or total absence of the posterior capsule. Yttrium aluminum garnet (YAG) laser capsulotomy permitted, if completed more than 3 months prior to screening, in the study eye * Subjects not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator´s opinion, makes the subject an unreliable trial subject) Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Single Rising Dose Part - Number of Subjects With Ocular Dose Limiting Events (DLEs) From Drug Administration Until Day 8 (7 Days After Treatment) | From initial drug administration (day 1) until day 8. | Dose limiting events were defined in the clinical trial protocol as any of the following occurrences in the eye being studied during the evaluation period: * development of sterile endophthalmitis and/or sterile inflammation of the vitreous of 3+ (out of 0, 0.5+,1+,2+,3+ and 4+, where 0 is clear vitreous and 4+ is an obscured vitreous) according to the NEI (National Eye Institute) Grading of vitreous haze, and anterior chamber cells of 3+ (out of 0, 0.5+,1+,2+,3+ and 4+, where 0 is no inflammation and 4+ is severe inflammation) according to the Standardization of Uveitis Nomenclature (SUN) working group (WG) grading scheme for 5 or more days; * visual loss of more than 15 letters at any given time-point; persistent intra-ocular pressure over 30 mmHg for 3 days; * and signs of vascular occlusion in a first (the main branch) or second degree (the vessel after the first bifurcation of the main branch) retinal vessel. |
| Multiple Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) From Drug Administration Until End of Study (EOS) | From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7. | Number of subjects with adverse events assessed as drug related by the investigator from first drug administration to end of the multiple dose part of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 5 | MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 85±7 (visit 5) is reported. | This outcome measured the change in size of the foveal avascular zone (FAZ) from baseline to visit 5 of the multiple dose part of the trial by optical coherence tomography angiography (OCTA). Results were calculated as \[Visit 5\] -\[Baseline\]. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors. |
| Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 6 | MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 113±7 (visit 6) is reported. | This outcome measured the change in size of the foveal avascular zone (FAZ) from baseline to visit 6 of the multiple dose part of the trial by optical coherence tomography angiography (OCTA). Results were calculated as \[Visit 6\] - \[Baseline\]. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors. |
| Single Rising Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) at End of Study (EOS) | From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7. | Number of subjects with adverse events assessed as drug related by the investigator from first drug administration to end of the single rising dose part of the study. |
| Multiple Dose Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7 | MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 141±7 (visit 7) is reported. | This outcome measured the absolute change in best corrected visual acuity (BCVA) from baseline to visit 7 of the multiple dose part of the trial. The BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity chart. The BCVA score was the number of letters read correctly by the patient. Results were calculated as \[Visit 7\] - \[Baseline\] and were rounded to one decimal place. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors. |
| Multiple Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) From Drug Administration Until End of Study (EOS) | From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7. | Number of subjects with any ocular adverse events at the end of the multiple dose part of the study. |
| Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 7 | MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 141±7 (visit 7) is reported. | This outcome measured the change in size of the foveal avascular zone (FAZ) from baseline to visit 7 of the multiple dose part of the trial by optical coherence tomography angiography (OCTA). Results were calculated as \[Visit 7\] - \[Baseline\]. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors. |
| Single Rising Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) at End of Study (EOS) | From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7. | Number of subjects with any ocular adverse events at the end of the single rising dose part of the study. |
Countries
Australia, Latvia, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was a trial consisting of a non-randomised, uncontrolled, open label single rising dose part (Part A) and a randomised, sham controlled, double-masked multiple doses part (Part B).
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. One eye was selected, according to inclusion /exclusion criteria, as the study eye to be treated.
Participants by arm
| Arm | Count |
|---|---|
| Single Rising Dose Part: Low-dose BI 765128 Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received one single intravitreal injection of low-dose BI 765128. | 3 |
| Single Rising Dose Part: Medium-dose BI 765128 Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received one single intravitreal injection of medium-dose BI 765128. | 3 |
| Single Rising Dose Part: High-dose BI 765128 Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received one single intravitreal injection of high-dose BI 765128. | 6 |
| Multiple Dose Part: Sham Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received 3 single intravitreal sham injection at week 1, 4 and 8. | 10 |
| Multiple Dose Part: High-dose BI 765128 Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received 3 single intravitreal injection of high-dose BI 765128 at week 1, 4 and 8. | 23 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Not treated | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Single Rising Dose Part: Low-dose BI 765128 | Single Rising Dose Part: Medium-dose BI 765128 | Single Rising Dose Part: High-dose BI 765128 | Multiple Dose Part: Sham | Multiple Dose Part: High-dose BI 765128 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 68.7 Years STANDARD_DEVIATION 9 | 50.7 Years STANDARD_DEVIATION 14.4 | 63.8 Years STANDARD_DEVIATION 6.7 | 52.0 Years STANDARD_DEVIATION 15.5 | 57.7 Years STANDARD_DEVIATION 12.4 | 57.5 Years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 5 Participants | 8 Participants | 19 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 4 Participants | 9 Participants | 21 Participants | 40 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 4 Participants | 4 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 6 Participants | 14 Participants | 27 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 10 | 0 / 23 |
| other Total, other adverse events | 1 / 3 | 1 / 3 | 3 / 6 | 5 / 10 | 3 / 23 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 0 / 6 | 2 / 10 | 3 / 23 |
Outcome results
Primary
Multiple Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) From Drug Administration Until End of Study (EOS)
Number of subjects with adverse events assessed as drug related by the investigator from first drug administration to end of the multiple dose part of the study.
Time frame: From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7.
Population: Treated set (TS) - multiple dose part: all subjects who were randomized and treated with at least one dose of study drug (either treatment with BI 765128 or Sham).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Rising Dose Part: Low-dose BI 765128 | Multiple Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) From Drug Administration Until End of Study (EOS) | 0 Participants |
| Single Rising Dose Part: Medium-dose BI 765128 | Multiple Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) From Drug Administration Until End of Study (EOS) | 1 Participants |
Primary
Single Rising Dose Part - Number of Subjects With Ocular Dose Limiting Events (DLEs) From Drug Administration Until Day 8 (7 Days After Treatment)
Dose limiting events were defined in the clinical trial protocol as any of the following occurrences in the eye being studied during the evaluation period: * development of sterile endophthalmitis and/or sterile inflammation of the vitreous of 3+ (out of 0, 0.5+,1+,2+,3+ and 4+, where 0 is clear vitreous and 4+ is an obscured vitreous) according to the NEI (National Eye Institute) Grading of vitreous haze, and anterior chamber cells of 3+ (out of 0, 0.5+,1+,2+,3+ and 4+, where 0 is no inflammation and 4+ is severe inflammation) according to the Standardization of Uveitis Nomenclature (SUN) working group (WG) grading scheme for 5 or more days; * visual loss of more than 15 letters at any given time-point; persistent intra-ocular pressure over 30 mmHg for 3 days; * and signs of vascular occlusion in a first (the main branch) or second degree (the vessel after the first bifurcation of the main branch) retinal vessel.
Time frame: From initial drug administration (day 1) until day 8.
Population: Treated set (TS) - single rising dose part: all subjects who were treated with at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Rising Dose Part: Low-dose BI 765128 | Single Rising Dose Part - Number of Subjects With Ocular Dose Limiting Events (DLEs) From Drug Administration Until Day 8 (7 Days After Treatment) | 0 Participants |
| Single Rising Dose Part: Medium-dose BI 765128 | Single Rising Dose Part - Number of Subjects With Ocular Dose Limiting Events (DLEs) From Drug Administration Until Day 8 (7 Days After Treatment) | 0 Participants |
| Single Rising Dose Part: High-dose BI 765128 | Single Rising Dose Part - Number of Subjects With Ocular Dose Limiting Events (DLEs) From Drug Administration Until Day 8 (7 Days After Treatment) | 0 Participants |
Secondary
Multiple Dose Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7
This outcome measured the absolute change in best corrected visual acuity (BCVA) from baseline to visit 7 of the multiple dose part of the trial. The BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity chart. The BCVA score was the number of letters read correctly by the patient. Results were calculated as \[Visit 7\] - \[Baseline\] and were rounded to one decimal place. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors.
Time frame: MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 141±7 (visit 7) is reported.
Population: Treated set (TS) - multiple dose part: all subjects who were randomized and treated with at least one dose of study drug (either treatment with BI 765128 or Sham). Only subjects with baseline and at least one on-treatment post baseline value were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Single Rising Dose Part: Low-dose BI 765128 | Multiple Dose Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7 | 1.1 Number of letters | Standard Error 1.9 |
| Single Rising Dose Part: Medium-dose BI 765128 | Multiple Dose Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7 | 1.3 Number of letters | Standard Error 1.3 |
95% CI: [-4.7, 5]
Secondary
Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 5
This outcome measured the change in size of the foveal avascular zone (FAZ) from baseline to visit 5 of the multiple dose part of the trial by optical coherence tomography angiography (OCTA). Results were calculated as \[Visit 5\] -\[Baseline\]. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors.
Time frame: MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 85±7 (visit 5) is reported.
Population: Treated set (TS) - multiple dose part: all subjects who were randomized and treated with at least one dose of study drug (either treatment with BI 765128 or Sham). Only subjects with baseline and at least one on-treatment post baseline value were included in the analysis. Only subjects with measurements with scan quality index 6 or higher were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Single Rising Dose Part: Low-dose BI 765128 | Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 5 | 0.0075 millimeter^2 | Standard Error 0.0302 |
| Single Rising Dose Part: Medium-dose BI 765128 | Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 5 | -0.0177 millimeter^2 | Standard Error 0.0225 |
95% CI: [-0.1048, 0.0545]
Secondary
Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 6
This outcome measured the change in size of the foveal avascular zone (FAZ) from baseline to visit 6 of the multiple dose part of the trial by optical coherence tomography angiography (OCTA). Results were calculated as \[Visit 6\] - \[Baseline\]. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors.
Time frame: MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 113±7 (visit 6) is reported.
Population: Treated set (TS) - multiple dose part: all subjects who were randomized and treated with at least one dose of study drug (either treatment with BI 765128 or Sham). Only subjects with baseline and at least one on-treatment post baseline value were included in the analysis. Only subjects with measurements with scan quality index 6 or higher were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Single Rising Dose Part: Low-dose BI 765128 | Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 6 | -0.0020 millimeter^2 | Standard Error 0.0189 |
| Single Rising Dose Part: Medium-dose BI 765128 | Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 6 | -0.0121 millimeter^2 | Standard Error 0.0142 |
95% CI: [-0.0625, 0.0422]
Secondary
Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 7
This outcome measured the change in size of the foveal avascular zone (FAZ) from baseline to visit 7 of the multiple dose part of the trial by optical coherence tomography angiography (OCTA). Results were calculated as \[Visit 7\] - \[Baseline\]. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors.
Time frame: MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 141±7 (visit 7) is reported.
Population: Treated set (TS) - multiple dose part: all subjects who were randomized and treated with at least one dose of study drug (either treatment with BI 765128 or Sham). Only subjects with baseline and at least one on-treatment post baseline value were included in the analysis. Only subjects with measurements with scan quality index 6 or higher were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Single Rising Dose Part: Low-dose BI 765128 | Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 7 | -0.0087 millimeter^2 | Standard Error 0.0135 |
| Single Rising Dose Part: Medium-dose BI 765128 | Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 7 | -0.0071 millimeter^2 | Standard Error 0.012 |
95% CI: [-0.0504, 0.0536]
Secondary
Multiple Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) From Drug Administration Until End of Study (EOS)
Number of subjects with any ocular adverse events at the end of the multiple dose part of the study.
Time frame: From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7.
Population: Treated set (TS) - multiple dose part: all subjects who were randomized and treated with at least one dose of study drug (either treatment with BI 765128 or Sham).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Rising Dose Part: Low-dose BI 765128 | Multiple Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) From Drug Administration Until End of Study (EOS) | 3 Participants |
| Single Rising Dose Part: Medium-dose BI 765128 | Multiple Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) From Drug Administration Until End of Study (EOS) | 9 Participants |
Secondary
Single Rising Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) at End of Study (EOS)
Number of subjects with any ocular adverse events at the end of the single rising dose part of the study.
Time frame: From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7.
Population: Treated set (TS) - single rising dose part: all subjects who were treated with at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Rising Dose Part: Low-dose BI 765128 | Single Rising Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) at End of Study (EOS) | 0 Participants |
| Single Rising Dose Part: Medium-dose BI 765128 | Single Rising Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) at End of Study (EOS) | 1 Participants |
| Single Rising Dose Part: High-dose BI 765128 | Single Rising Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) at End of Study (EOS) | 1 Participants |
Secondary
Single Rising Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) at End of Study (EOS)
Number of subjects with adverse events assessed as drug related by the investigator from first drug administration to end of the single rising dose part of the study.
Time frame: From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7.
Population: Treated set (TS) - single rising dose part: all subjects who were treated with at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Rising Dose Part: Low-dose BI 765128 | Single Rising Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) at End of Study (EOS) | 0 Participants |
| Single Rising Dose Part: Medium-dose BI 765128 | Single Rising Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) at End of Study (EOS) | 0 Participants |
| Single Rising Dose Part: High-dose BI 765128 | Single Rising Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) at End of Study (EOS) | 0 Participants |