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 Dosing (Single-masked, raNdomized, Sham-controlled) of BI 764524 in panretinaL Photocoagulation (PRP) Treated proLiferative Diabetic Retinopathy (PDR) Patients With Diabetic Macular Ischemia (DMI) - the HORNBILL Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 18
- 主要终点
- Single-rising Dose (SRD) Part - The Number of Patients With Dose Limiting Events (DLEs) From Drug Administration Until Day 8
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
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).
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 exclusion criteria apply.
- •MD part only:
- •DME, defined as a central subfield thickness (CST) ≥305 micrometer (μm) for men and ≥290 μm women measured with optovue (Optical coherent tomography) OCT in the study eye
- •Participants receiving IVT injections for active DME (anti-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
- •Heavily lasered macula in the study eye per investigator's judgement
- •History of vitrectomy in the study eye
- •Epiretinal membrane with extended foveal contour distortion in the study eye per investigator's judgement
- •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) Further exclusion criteria apply.
研究组 & 干预措施
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.
干预措施: Sham control of BI 764524 (Drug)
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.
干预措施: BI 764524 (Drug)
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.
干预措施: BI 764524 (Drug)
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.
干预措施: BI 764524 (Drug)
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.
干预措施: BI 764524 (Drug)
结局指标
主要结局
Single-rising Dose (SRD) Part - The Number of Patients With Dose Limiting Events (DLEs) From Drug Administration Until Day 8
时间窗: 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.
时间窗: 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.
次要结局
- 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 FAZ in SVC at Visit 7(Baseline (day 0) and Visit 7 (day 155±7).)
- 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.)
- 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 - 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 Best Corrected Visual Acuity (BCVA) at Visit 4(Baseline (day 0) and Visit 4 (day 57±7).)
- 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) at Visit 5(Baseline (day 0) and Visit 5 (day 85±7).)
- 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.)
- 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 Best Corrected Visual Acuity (BCVA) at Visit 6(Baseline (day 0) and Visit 6 (day 113±7).)
- MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7(Baseline (day 0) and Visit 7 (day 155±7).)
- 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 Best Corrected Visual Acuity (BCVA) at Visit 3(Baseline (day 0) and Visit 3 (day 29±7).)
- 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 Best Corrected Visual Acuity (BCVA) at Visit 5(Baseline (day 0) and Visit 5 (day 85±7).)
- MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 6(Baseline (day 0) and Visit 6 (day 113±7).)