Macular Edema
Conditions
Brief summary
This is a proof of mechanism trial to explore the effect of BI 1026706 on the central retinal thickness and to evaluate safety and tolerability of BI 1026706 administered orally for 12 weeks in patients with mild vision impairment due to center-involved DME
Interventions
DRUGBI 1026706
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients 18 years of age and older * Male patients or female patients of non-childbearing potential * Diagnosis of Diabetes mellitus type 1 or type 2 * Retinal thickening due to Diabetic macular edema (DME) involving the center of the macula in the study eye as confirmed by the Investigator on clinical exam * Center-involved DME confirmed on Spectral-Domain Optical Coherence Tomography (SD-OCT) with central subfield thickness (CSFT) of at least 300 µm in the study eye at screening, confirmed by Central Reading Centre * Best corrected visual acuity ETDRS (Early Treatment Diabetic Retinopathy Study) letter score in the study eye of 84 or below, but at least 70 at screening * Further inclusion criteria apply
Exclusion criteria
* Macular edema considered to be due to other causes than DME in the study eye * Additional eye disease in the study eye that, in the opinion of the Investigator, might affect macular edema or could compromise or alter visual acuity during the course of the trial * Anterior segment and vitreous abnormalities in the study eye that would compromise the adequate assessment of the best corrected visual acuity or an adequate examination of the posterior pole * Intraocular surgery in the study eye within 4 months prior to randomization or planned intraocular surgery, including cataract, during the study period * Proliferative diabetic retinopathy or iris neovascularisation in the study eye * Aphakia in the study eye * Any indication that requires immediate treatment or for which treatment is expected in the study eye with anti-Vascular Endothelial Growth Factor (VEGF) or with laser photocoagulation during the period, as per Investigator's judgment * History of prior laser photocoagulation or other surgical, intravitreal or peribulbar treatment in the study eye within 4 months prior to randomization, either for DME or an ocular condition other than DME * History of fluocinolone acetonide intravitreal implant in the study eye * Application of intraocular corticosteroids in the study eye within 2 years prior to randomization in phakic eyes or 9 months in pseudophakic eyes * History of topical steroid or nonsteroidal anti-inflammatory drugs (NSAID) treatment in the study eye within 30 days prior to randomization * Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization * Initiation of intensive insulin treatment (multiple daily injections or a pump) within 3 months prior to randomization or plans to do so in the next 4 months * Change in oral antidiabetic medication within 3 months prior to randomization * Patients with a clinically relevant abnormal screening haematology, blood chemistry, or urinalysis * Renal impairment with estimated creatinine clearance \< 30 mL/min (as calculated by Cockcroft-Gault equation) * Myocardial infarction or unstable angina pectoris within 3 months before randomization * Uncontrolled arterial hypertension defined as a single measurement of systolic \>180 mmHg, two consecutive measurements of systolic \>160 mmHg, or diastolic \>100mmHg on optimal medical regimen * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Central Subfield Foveal Thickness (CSFT) at Week 12 | Baseline and Week 12 | The change from baseline in CSFT at Week 12 and the BI 1026706 effect was compared between the BI 1026706 treatment group and the placebo group as measured by Spectral-domain Optical Coherence Tomography (SD-OCT). Baseline was defined as the CSFT value measured at the visit when patients were randomised. Mean presented here is an adjusted mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | From first drug administration until 4 days after last drug administration, up to 89 days. | Number of subjects with serious adverse events (SAEs), Investigator defined drug-related Adverse events (AEs) and adverse events of special interest (AESIs) comparing the BI 1026706 treatment group with the placebo group is presented. |
Countries
Belgium, France, Germany, Greece, Hungary, Portugal, Spain, United Kingdom
Participant flow
Recruitment details
This was randomised, double-blind, placebo-controlled, parallel-group trial to evaluate pharmacodynamics, safety and tolerability of orally administered Boehringer Ingelheim (BI) 1026706 for 12 weeks in patients with Diabetic Macular Oedema (DME).
Pre-assignment details
All patients were screened for eligibility to participate in the trial. Patients attended specialist sites which would then ensure that all patients met all inclusion/exclusion criteria. Patients were not to be randomized to trial treatment if any one of the specific entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching to BI 1026706 Patients were administered film-coated tablet of placebo to match 100 mg BI 1026706 twice daily orally for 12 weeks. | 53 |
| BI 1026706 Patients were administered film-coated tablet of 100 mg BI 1026706 twice daily orally for 12 weeks. | 52 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other than listed | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | BI 1026706 | Total | Placebo Matching to BI 1026706 |
|---|---|---|---|
| Age, Continuous | 63.9 Years STANDARD_DEVIATION 8.7 | 63.0 Years STANDARD_DEVIATION 9.2 | 62.2 Years STANDARD_DEVIATION 9.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 78 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 19 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 19 Participants | 14 Participants |
| Race (NIH/OMB) White | 47 Participants | 85 Participants | 38 Participants |
| Sex: Female, Male Female | 14 Participants | 28 Participants | 14 Participants |
| Sex: Female, Male Male | 38 Participants | 77 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 52 |
| other Total, other adverse events | 12 / 53 | 14 / 52 |
| serious Total, serious adverse events | 2 / 53 | 7 / 52 |
Outcome results
Primary
Change From Baseline in Central Subfield Foveal Thickness (CSFT) at Week 12
The change from baseline in CSFT at Week 12 and the BI 1026706 effect was compared between the BI 1026706 treatment group and the placebo group as measured by Spectral-domain Optical Coherence Tomography (SD-OCT). Baseline was defined as the CSFT value measured at the visit when patients were randomised. Mean presented here is an adjusted mean.
Time frame: Baseline and Week 12
Population: Full analysis set (FAS): FAS includes all patients who were randomised, treated with at least 1 dose of BI 1026706 or placebo, and with a baseline and at least one post randomisation central subfield foveal thickness (CSFT) measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI 1026706 | Change From Baseline in Central Subfield Foveal Thickness (CSFT) at Week 12 | -6.19 Micrometre [μm] | Standard Deviation 11.61 |
| BI 1026706 | Change From Baseline in Central Subfield Foveal Thickness (CSFT) at Week 12 | 10.26 Micrometre [μm] | Standard Deviation 11.64 |
Comparison: Null hypothesis = The CSFT change from baseline at Week 12 is equal in both groupsp-value: 0.319995% CI: [-16.23, 49.13]Mixed model for repeated measurements
Secondary
Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
Number of subjects with serious adverse events (SAEs), Investigator defined drug-related Adverse events (AEs) and adverse events of special interest (AESIs) comparing the BI 1026706 treatment group with the placebo group is presented.
Time frame: From first drug administration until 4 days after last drug administration, up to 89 days.
Population: Treated set (TS): TS includes all patients who were treated with at least 1 dose of trial drug, either BI 1026706 or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matching to BI 1026706 | Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Total with SAEs | 2 Count of participants |
| Placebo Matching to BI 1026706 | Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Investigator defined drug-related AE | 7 Count of participants |
| Placebo Matching to BI 1026706 | Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | AESIs | 0 Count of participants |
| BI 1026706 | Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Total with SAEs | 7 Count of participants |
| BI 1026706 | Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Investigator defined drug-related AE | 7 Count of participants |
| BI 1026706 | Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | AESIs | 1 Count of participants |