Clinical trial NCT04919499: A Study of BI 765128 in Patients With an Eye Condition Called Diabetic Macular Ischemia Who Have Received Laser Treatment
Official title: A First in Human Trial to Study Safety and Tolerability of Single Rising Intravitreal Doses (oPen Label, Non-randomized, Uncontrolled) and in Addition the Early Biological Response of mulTiple Intravitreal Doses (Double-masked, RandomIzed, Sham-controlleD) of BI 765128 in Panretinal photocoaGulation (PRP) Treated Diabetic rEtinopathy (DR) Patients With Diabetic Macular Ischemia (DMI) - the PARTRIDGE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diabetic Retinopathy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-06-09
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 exclusion criteria apply

Part B:

* Diabetic Macular Edema (DME), defined as a Central Subfield Thickness (CST) ≥ 305μm for men and ≥ 290 μm for women (Optovue Angiovue) in the study eye
* Subjects receiving intravitreal (IVT) injections for active 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 intravitreal IVT injections for active Diabetic Retinopathy (DR) in the previous 3 months to screening in the study eye
* Heavily lasered macula in the study eye per investigator judgement
* History of vitrectomy in the study eye
* Epiretinal membrane with extended foveal contour distortion 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 eye disease in the study eye that could compromise best corrected VA (BCVA). Significant visual field loss, uncontrolled glaucoma (IOP\>24), clinically significant diabetic maculopathy, 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 and OCTA Further exclusion criteria apply

Primary outcomes:
measure: Single Rising Dose Part - Number of Subjects With Ocular Dose Limiting Events (DLEs) From Drug Administration Until Day 8 (7 Days After Treatment)
timeFrame: From initial drug administration (day 1) until day 8.
measure: Multiple Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) From Drug Administration Until End of Study (EOS)
timeFrame: From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7.
Secondary outcomes:
measure: Single Rising Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) at End of Study (EOS)
timeFrame: From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7.
measure: Single Rising Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) at End of Study (EOS)
timeFrame: From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7.
measure: Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 5
timeFrame: 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.
measure: Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 6
timeFrame: 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.
measure: Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 7
timeFrame: 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.
measure: Multiple Dose Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7
timeFrame: 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.
measure: Multiple Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) From Drug Administration Until End of Study (EOS)
timeFrame: From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7.
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates - Walnut Creek
state: California
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants, PC.
state: Maryland
city: Cincinnati
country: United States
facility: Meridian Clinical Research, LLC
state: Ohio
city: Erie
country: United States
facility: Erie Retina Research, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: Austin
country: United States
facility: Austin Research Center for Retina, PLLC
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research, LLC
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Adelaide
country: Australia
facility: Adelaide Eye and Retina Centre
state: South Australia
city: Hobart
country: Australia
facility: Hobart Eye Surgeons
state: Tasmania
city: Riga
country: Latvia
facility: Riga East University Hospital
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum (LUMC)
city: Barcelona
country: Spain
facility: Hospital Dos de Maig
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: London
country: United Kingdom
facility: Central Middlesex Hospital
city: Oxford
country: United Kingdom
facility: Oxford Eye Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
Study officials:
References: