HORNBILL: A Study to Test Different Doses of BI 764524 in Patients Who Have Had Laser Treatment for a Type of Diabetic Eye Disease Called Diabetic Retinopathy With Diabetic Macular Ischemia

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04424290
Collaborator
(none)
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: BI 764524
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
48 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
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).
Primary Purpose:
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 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
Actual Study Start Date :
Jun 12, 2020
Anticipated Primary Completion Date :
Jan 17, 2023
Anticipated Study Completion Date :
Apr 17, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: BI 764524

Single rising dose part followed by a multiple dosing part.

Drug: BI 764524
Powder for solution for intravitreal injection.

Outcome Measures

Primary Outcome Measures

  1. Single rising dose (SRD) part: Number of participants with dose limiting events [14 weeks]

    Number of patients with dose limiting events (DLEs) from drug administration till day 8 (7 days after treatment).

  2. Multiple dosing (MD) part: Number of patients with drug related adverse events (AEs) from drug administration till end of study (EOS) [22 weeks]

Secondary Outcome Measures

  1. SRD part: Number of patients with drug related AEs at EOS [14 weeks]

  2. SRD part: Number of patients with ocular AEs (eye disorders) at EOS [14 weeks]

  3. MD part: Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in superficial and combined vascular complex at Visit 5 [12 weeks]

  4. MD part: Change from baseline of the size of the FAZ in OCTA in superficial and combined vascular complex at Visit 7 [22 weeks]

  5. MD part: Change from baseline of best corrected visual acuity (BCVA) at Visit 3 [4 weeks]

  6. MD part: Change from baseline of BCVA at Visit 4 [8 weeks]

  7. MD part: Change from baseline of BCVA at Visit 5 [12 weeks]

  8. MD part: Change from baseline of BCVA at Visit 6 [16 weeks]

  9. MD part: Change from baseline of BCVA at Visit 7 [22 weeks]

  10. MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 3 [4 weeks]

  11. MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 4 [8 weeks]

  12. MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 5 [12 weeks]

  13. MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 6 [16 weeks]

  14. MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 7 [22 weeks]

  15. MD part: Number of patients with ocular AEs at EOS [22 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Trinity Research Dothan Alabama United States 36301
2 Retina-Vitreous Associates Medical Group Beverly Hills California United States 90211
3 Stanford University Medical Center Palo Alto California United States 94303
4 Florida Retina Institute Orlando Florida United States 32806
5 Raj K. Maturi, MD PC Carmel Indiana United States 46290
6 Joslin Diabetes Center Boston Massachusetts United States 02115
7 Long Island Vitreoretinal Consultants Great Neck New York United States 11021
8 New York Eye and Ear Infirmary of Mount Sinai New York New York United States 10003
9 Cleveland Clinic Cleveland Ohio United States 44195
10 Retina Research Institute of Texas Abilene Texas United States 79606
11 Austin Research Center for Retina, PLLC Austin Texas United States 78705
12 Retina Consultants of Texas Bellaire Texas United States 77401
13 Valley Retina Institute, PA McAllen Texas United States 78503
14 Retina Consultants of Texas The Woodlands Texas United States 77384
15 Emerson Clinical Research Institute Falls Church Virginia United States 22042
16 Bradford Royal Infirmary Bradford United Kingdom BD9 6RJ
17 Bristol Eye Hospital Bristol United Kingdom BS1 2LX
18 Gloucestershire Royal Hospital Gloucester United Kingdom GL1 3NN
19 Moorfields Eye Hospital London United Kingdom EC1V 2PD
20 Sunderland Eye Infirmary Sunderland United Kingdom SR2 9HP
21 Southend General Hospital Westcliff-on-Sea United Kingdom SS0 0RY

Sponsors and Collaborators

  • Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT04424290
Other Study ID Numbers:
  • 1436-0001
  • 2019-004432-28
First Posted:
Jun 9, 2020
Last Update Posted:
Aug 23, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 23, 2022