Diabetic Retinopathy
Conditions
Brief summary
This is a study in people with a type of diabetic eye disease called diabetic retinopathy with diabetic macular ischemia. People who have had laser treatment for their diabetic retinopathy can participate in the study. The laser treatment is called panretinal photocoagulation. The purpose of the study is to find out how well different doses of a medicine called BI 764524 are tolerated. BI 764524 is injected into the eye. The study has 2 parts. In the first part, participants get different doses of BI 764524 only once. Participants are in the first part for about 5 months and visit the study site about 8 times. In the second part, participants are put into different groups by chance. Some participants get BI 764524 injections every 4 weeks. Other participants get sham injections every 4 weeks. 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. For the second part, participants are in the study for about 7 months. During this time, they visit the study site about 7 times. In this study, BI 764524 is given to humans for the first time. The doctors compare how well people tolerate the BI 764524 injections and the sham injections. The doctors also regularly check the general health of the participants.
Interventions
DRUGBI 764524
BI 764524
DRUGSham control of BI 764524
Sham control of BI 764524
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This trial will consist of an single rising dose (SRD) part followed by an multiple dosing (MD) part. SRD part will be nonrandomized, open-label, and uncontrolled. MD part will be single-masked, randomized and sham-controlled (Ratio 2:1). Parties masked in the MD part are participant and masked site staff (including investigator). The Intervention model in the MD part is active group versus sham injection (=2 arms).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Single rising dose (SRD) and multiple dosing (MD) part: * Pan-retinal photo coagulation treated proliferative diabetic retinopathy (PDR) participants with either no or inactive retinal neovascularization per investigator judgement in the study eye * Male or female participants of age ≥ 18 years * HbA1c of ≤ 12.0% * 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 methods 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. A list of contraception methods meeting these criteria is provided in the patient information and in the clinical trial protocol. --A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal ligation is NOT a method of permanent sterilisation. A postmenopausal state is defined as no menses for 2 years without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 2 years of menorrhea, a single FSH measurement is sufficient. * Signed and dated written informed consent in accordance with ICH Harmonized Guideline for Good Clinical Practice (ICH GCP) and local legislation prior to admission to the trial SRD part only: * Evidence of diabetic macular ischemia (DMI) per investigator´s judgement, defined as any degree of disruption of retinal vascularity in superficial and/or deep retinal plexus in OCTA * Best-corrected Visual activity (VA) in the non-study eye better than best-corrected VA in the study-eye, if both eyes are eligible and have identical VA the investigator may select the study eye. * Best-corrected VA ≤55 letters (20/80) or worse MD part only: * Presence of significant DMI: large foveal avascular zone defined as those with ≥0.5mm2 area in superficial vascular complex (SVC) present on optical coherence tomography angiography. If FAZ is \<0.5mm2 then enlarged peri-foveal inter-capillary space in at least 1 quadrant will be sufficient. * If both eyes are eligible, the investigator may select either eye to be the study eye. * Best-corrected VA ≤ 85 letters (20/20) or worse
Exclusion criteria
SRD part only: * Participants receiving intravitreal (IVT) injections for active diabetic macular edema (DME, injections: anti-vascular endothelial growth factor (VEGF), steroids) and macular laser in the study eye in the previous 3 months prior to enrolment * Participants receiving anti-VEGF IVT injections for active PDR in the study eye in the previous 3 months prior to enrolment * Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol) * Additional eye disease in the study eye that could compromise best corrected VA (BCVA) with visual field loss, uncontrolled glaucoma (IOP\>24), age related macular degeneration, history of ischemic optic neuropathy or retinal vascular occlusion, symptomatic vitreomacular traction, or genetic disorders such as retinitis pigmentosa; 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 SD-OCT * Any intraocular surgery in the study eye within 3 months prior to screening * Aphakia or total absence of the posterior capsule. Yttrium aluminium garnet (YAG) laser capsulotomy in the study eye if performed less than 3 months prior to enrolment * Participants 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 patient an unreliable trial participant) * Previous participation in this trial or in other trials with IVT injections administered within 3 months. Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Single-rising Dose (SRD) Part - The Number of Patients With Dose Limiting Events (DLEs) From Drug Administration Until Day 8 | From drug administration (day 1) till day 8, Up to 7±2 days. | Single-rising dose (SRD) part - The number of patients with dose limiting events (DLEs) from drug administration until Day 8 (7 days after treatment). |
| Multiple Dosing (MD) Part - the Number of Patients With Drug-related Adverse Events (AEs) From Drug Administration Until End of Trial. | From drug administration (day 1) till End of Trial, up to 23 weeks. | Multiple dosing (MD) part - the number of patients with drug-related Adverse Events (AEs) from drug administration until End of Trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial | From drug administration (day 1) till End of Trial, up to 23 weeks. | MD part - Number of patients with ocular Adverse Events (eye disorders) at End of Trial. |
| MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 5 | Baseline (day 0) and Visit 5 (day 85±7). | MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in full thickness retina (FTR) at Visit 5. Results calculated as \[Baseline data\]-\[Visit 5 data\]. |
| MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 5 | Baseline (day 0) and Visit 5 (day 85±7). | MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in superficial vascular complex (SVC) at Visit 5. Results calculated as \[Baseline data\]-\[Visit 5 data\]. |
| MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 7 | Baseline (day 0) and Visit 7 (day 155±7). | MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in full thickness retina (FTR) at Visit 7. Results calculated as \[Baseline data\]-\[Visit 7 data\]. |
| MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 7 | Baseline (day 0) and Visit 7 (day 155±7). | MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in superficial vascular complex (SVC) at Visit 7. Results calculated as \[Baseline data\]-\[Visit 7 data\]. |
| MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 3 | Baseline (day 0) and Visit 3 (day 29±7). | Change from baseline of best corrected visual acuity (BCVA) at Visit 3. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 3 data\]. |
| MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 4 | Baseline (day 0) and Visit 4 (day 57±7). | Change from baseline of best corrected visual acuity (BCVA) at Visit 4. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 4 data\]. |
| SRD Part - Number of Patients With Drug-related Adverse Events at End of Trial | From drug administration (day 1) till End of Trial, up to 15 weeks. | SRD part - Number of patients with drug-related Adverse Events at End of Trial. |
| MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 6 | Baseline (day 0) and Visit 6 (day 113±7). | Change from baseline of best corrected visual acuity (BCVA) at Visit 6. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 6 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 6 data\]. |
| MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7 | Baseline (day 0) and Visit 7 (day 155±7). | Change from baseline of best corrected visual acuity (BCVA) at Visit 7. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 7 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 7 data\]. |
| MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 3 | Baseline (day 0) and Visit 3 (day 29±7). | MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 3. Results calculated as \[Baseline data\]-\[Visit 3 data\]. |
| MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 4 | Baseline (day 0) and Visit 4 (day 57±7) | MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 4. Results calculated as \[Baseline data\]-\[Visit 4 data\]. |
| MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 5 | Baseline (day 0) and Visit 5 (day 85±7). | MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 5. Results calculated as \[Baseline data\]-\[Visit 5 data\]. |
| MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 6 | Baseline (day 0) and Visit 6 (day 113±7). | MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 6. Results calculated as \[Baseline data\]-\[Visit 6 data\]. |
| MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 7 | Baseline (day 0) and Visit 7 (day 155±7). | MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 7. Results calculated as \[Baseline data\]-\[Visit 7 data\]. |
| MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 5 | Baseline (day 0) and Visit 5 (day 85±7). | Change from baseline of best corrected visual acuity (BCVA) at Visit 5. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 5 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 5 data\]. |
| SRD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial | From drug administration (day 1) till End of Trial, up to 15 weeks. | SRD part - Number of patients with ocular Adverse Events (eye disorders) at End of Trial. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
This was a trial consisting of a non-randomised, uncontrolled, open label single-rising dose part and a randomised, shamcontrolled, single-blind multiple dosing part.
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. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Single-rising Dose Part - Low Dose BI 764524 Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of low dose BI 764524. | 3 |
| Single-rising Dose Part - Medium Dose BI 764524 Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of medium dose BI 764524. | 3 |
| Single-rising Dose Part - High Dose BI 764524 Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of high dose BI 764524. | 6 |
| Multiple Dosing Part - Sham Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks. | 10 |
| Multiple Dosing Part - High Dose BI 764524 Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks. | 21 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Not treated | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Other than listed | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Single-rising Dose Part - Low Dose BI 764524 | Single-rising Dose Part - Medium Dose BI 764524 | Single-rising Dose Part - High Dose BI 764524 | Multiple Dosing Part - Sham | Multiple Dosing Part - High Dose BI 764524 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 15 | 61.0 years STANDARD_DEVIATION 7 | 60.8 years STANDARD_DEVIATION 6 | 60.0 years STANDARD_DEVIATION 6.5 | 59.3 years STANDARD_DEVIATION 13.2 | 60.2 years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 3 Participants | 6 Participants | 19 Participants | 33 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 | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 4 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 | 1 Participants | 2 Participants | 6 Participants | 9 Participants | 17 Participants | 35 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 5 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 4 Participants | 5 Participants | 11 Participants | 22 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 / 21 |
| other Total, other adverse events | 3 / 3 | 1 / 3 | 5 / 6 | 6 / 10 | 6 / 21 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 1 / 6 | 3 / 10 | 2 / 21 |
Outcome results
Primary
Multiple Dosing (MD) Part - the Number of Patients With Drug-related Adverse Events (AEs) From Drug Administration Until End of Trial.
Multiple dosing (MD) part - the number of patients with drug-related Adverse Events (AEs) from drug administration until End of Trial.
Time frame: From drug administration (day 1) till End of Trial, up to 23 weeks.
Population: Treated set: all patients who were randomised and treated with at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | Multiple Dosing (MD) Part - the Number of Patients With Drug-related Adverse Events (AEs) From Drug Administration Until End of Trial. | 0 Participants |
| Single-rising Dose Part - Medium Dose BI 764524 | Multiple Dosing (MD) Part - the Number of Patients With Drug-related Adverse Events (AEs) From Drug Administration Until End of Trial. | 2 Participants |
Primary
Single-rising Dose (SRD) Part - The Number of Patients With Dose Limiting Events (DLEs) From Drug Administration Until Day 8
Single-rising dose (SRD) part - The number of patients with dose limiting events (DLEs) from drug administration until Day 8 (7 days after treatment).
Time frame: From drug administration (day 1) till day 8, Up to 7±2 days.
Population: Treated set: all patients who were randomised and treated with at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | Single-rising Dose (SRD) Part - The Number of Patients With Dose Limiting Events (DLEs) From Drug Administration Until Day 8 | 0 Participants |
| Single-rising Dose Part - Medium Dose BI 764524 | Single-rising Dose (SRD) Part - The Number of Patients With Dose Limiting Events (DLEs) From Drug Administration Until Day 8 | 0 Participants |
| Single-rising Dose Part - High Dose BI 764524 | Single-rising Dose (SRD) Part - The Number of Patients With Dose Limiting Events (DLEs) From Drug Administration Until Day 8 | 0 Participants |
Secondary
MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 3
Change from baseline of best corrected visual acuity (BCVA) at Visit 3. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 3 data\].
Time frame: Baseline (day 0) and Visit 3 (day 29±7).
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 3 | 1.5 Number of letters | Standard Deviation 13.5 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 3 | 1.1 Number of letters | Standard Deviation 5.2 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-8.1, 5.5]
Secondary
MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 4
Change from baseline of best corrected visual acuity (BCVA) at Visit 4. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 4 data\].
Time frame: Baseline (day 0) and Visit 4 (day 57±7).
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 4 | -4.1 Number of letters | Standard Deviation 24.4 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 4 | 1.4 Number of letters | Standard Deviation 6 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-7.3, 16.2]
Secondary
MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 5
Change from baseline of best corrected visual acuity (BCVA) at Visit 5. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 5 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 5 data\].
Time frame: Baseline (day 0) and Visit 5 (day 85±7).
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 5 | 3.9 Number of letters | Standard Deviation 10.7 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 5 | 2.5 Number of letters | Standard Deviation 6.5 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-9.6, 3]
Secondary
MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 6
Change from baseline of best corrected visual acuity (BCVA) at Visit 6. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 6 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 6 data\].
Time frame: Baseline (day 0) and Visit 6 (day 113±7).
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 6 | 2.6 Number of letters | Standard Deviation 9.6 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 6 | 3.1 Number of letters | Standard Deviation 9.8 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-7.3, 6.1]
Secondary
MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7
Change from baseline of best corrected visual acuity (BCVA) at Visit 7. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 7 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as \[Baseline data\]-\[Visit 7 data\].
Time frame: Baseline (day 0) and Visit 7 (day 155±7).
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7 | 4.9 Number of letters | Standard Deviation 9.3 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7 | 3.4 Number of letters | Standard Deviation 7.5 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-8.7, 3.1]
Secondary
MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 3
MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 3. Results calculated as \[Baseline data\]-\[Visit 3 data\].
Time frame: Baseline (day 0) and Visit 3 (day 29±7).
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 3 | 1.6 Micrometer | Standard Deviation 4.9 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 3 | 0.9 Micrometer | Standard Deviation 7.2 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-4.9, 5.4]
Secondary
MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 4
MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 4. Results calculated as \[Baseline data\]-\[Visit 4 data\].
Time frame: Baseline (day 0) and Visit 4 (day 57±7)
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 4 | -1.7 Micrometer | Standard Deviation 5.1 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 4 | 0.2 Micrometer | Standard Deviation 7.2 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-2.7, 7.9]
Secondary
MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 5
MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 5. Results calculated as \[Baseline data\]-\[Visit 5 data\].
Time frame: Baseline (day 0) and Visit 5 (day 85±7).
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 5 | -2.9 Micrometer | Standard Deviation 5.3 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 5 | 3.9 Micrometer | Standard Deviation 12.8 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-1.2, 16.5]
Secondary
MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 6
MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 6. Results calculated as \[Baseline data\]-\[Visit 6 data\].
Time frame: Baseline (day 0) and Visit 6 (day 113±7).
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 6 | -3.0 Micrometer | Standard Deviation 3.8 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 6 | 8.6 Micrometer | Standard Deviation 25.1 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-2.3, 29.8]
Secondary
MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 7
MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 7. Results calculated as \[Baseline data\]-\[Visit 7 data\].
Time frame: Baseline (day 0) and Visit 7 (day 155±7).
Population: All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 7 | -3.2 Micrometer | Standard Deviation 7.4 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 7 | 3.5 Micrometer | Standard Deviation 9.5 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-0.9, 14.5]
Secondary
MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 5
MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in full thickness retina (FTR) at Visit 5. Results calculated as \[Baseline data\]-\[Visit 5 data\].
Time frame: Baseline (day 0) and Visit 5 (day 85±7).
Population: All patients who were randomised and treated with at least one dose of study drug and with baseline and at least 1 on-treatment post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 5 | 0.0167 Millimeter^2 | Standard Deviation 0.0197 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 5 | -0.0004 Millimeter^2 | Standard Deviation 0.0381 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-0.0558, 0.0089]
Secondary
MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 7
MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in full thickness retina (FTR) at Visit 7. Results calculated as \[Baseline data\]-\[Visit 7 data\].
Time frame: Baseline (day 0) and Visit 7 (day 155±7).
Population: All patients who were randomised and treated with at least one dose of study drug and with baseline and at least 1 on-treatment post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 7 | 0.0133 Millimeter^2 | Standard Deviation 0.0152 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 7 | -0.0027 Millimeter^2 | Standard Deviation 0.0345 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-0.0412, 0.0195]
Secondary
MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 5
MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in superficial vascular complex (SVC) at Visit 5. Results calculated as \[Baseline data\]-\[Visit 5 data\].
Time frame: Baseline (day 0) and Visit 5 (day 85±7).
Population: All patients who were randomised and treated with at least one dose of study drug and with baseline and at least 1 on-treatment post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 5 | 0.0489 Millimeter^2 | Standard Deviation 0.074 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 5 | 0.0741 Millimeter^2 | Standard Deviation 0.113 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-0.067, 0.11]
Secondary
MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 7
MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in superficial vascular complex (SVC) at Visit 7. Results calculated as \[Baseline data\]-\[Visit 7 data\].
Time frame: Baseline (day 0) and Visit 7 (day 155±7).
Population: All patients who were randomised and treated with at least one dose of study drug and with baseline and at least 1 on-treatment post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 7 | 0.1233 Millimeter^2 | Standard Deviation 0.1473 |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 7 | 0.1101 Millimeter^2 | Standard Deviation 0.1445 |
Comparison: The Mixed model with repeated measurements (MMRM) model included the fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit were 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.95% CI: [-0.1477, 0.1021]
Secondary
MD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial
MD part - Number of patients with ocular Adverse Events (eye disorders) at End of Trial.
Time frame: From drug administration (day 1) till End of Trial, up to 23 weeks.
Population: Treated set: all patients who were randomised and treated with at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | MD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial | 4 Participants |
| Single-rising Dose Part - Medium Dose BI 764524 | MD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial | 4 Participants |
Secondary
SRD Part - Number of Patients With Drug-related Adverse Events at End of Trial
SRD part - Number of patients with drug-related Adverse Events at End of Trial.
Time frame: From drug administration (day 1) till End of Trial, up to 15 weeks.
Population: Treated set: all patients who were randomised and treated with at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | SRD Part - Number of Patients With Drug-related Adverse Events at End of Trial | 0 Participants |
| Single-rising Dose Part - Medium Dose BI 764524 | SRD Part - Number of Patients With Drug-related Adverse Events at End of Trial | 0 Participants |
| Single-rising Dose Part - High Dose BI 764524 | SRD Part - Number of Patients With Drug-related Adverse Events at End of Trial | 0 Participants |
Secondary
SRD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial
SRD part - Number of patients with ocular Adverse Events (eye disorders) at End of Trial.
Time frame: From drug administration (day 1) till End of Trial, up to 15 weeks.
Population: Treated set: all patients who were randomised and treated with at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-rising Dose Part - Low Dose BI 764524 | SRD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial | 2 Participants |
| Single-rising Dose Part - Medium Dose BI 764524 | SRD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial | 0 Participants |
| Single-rising Dose Part - High Dose BI 764524 | SRD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial | 3 Participants |