First-in Human trial of BI 764524 in diabetic retinopathy
Research type
Research Study
Full 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 rising intravitReal doses (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
IRAS ID
278921
Contact name
Abosede Cole
Contact email
Eudract number
2019-004432-28
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
2 years, 0 months, 7 days
Research summary
Research Summary:
This is 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 ischaemia. The study has two parts to it, a Single Rising Dose (SRD) and a Multiple Rising Dose (MRD) part. This is the first time that BI 764524 will be given to humans and 50 participants are planned to take part globally. In the UK it is planned that 3 participants will receive treatment in the SRD part of the study and 5 participants will take part in the MRD part.
It is planned to investigate up to 4 rising doses of BI 764524 in the SRD part with 3 patients per cohort. For each cohort, a single patient will be dosed and in the event that no serious adverse events occur then the remaining 2 patients will be dosed.
This will be followed by the MRD part which will consist of two dose cohorts. There will be 15 patients in each cohort, 10 of which will receive active treatment and 5 receiving a sham injection. In the MRD cohorts, patients will receive three consecutive doses/sham injection over a 3-month period. Dose escalation will be reviewed after 3 active patients from the first MRD cohort have completed visit 5.
The SRD part of the study will require 8 visits to the study clinic over ~18 weeks and MRD consists of 7 visits over ~26 weeks. Participants will be required to undergo various blood tests, Opthalmological assessments, ECGs, physical examinations, as well as safety and medication monitoring throughout the trial. Participants are not expected to receive any benefit from participating in this trial but may contribute new information that could benefit other patients in future.Summary of Results:
What was this study about?
The purpose of this study was to find out if participants could tolerate different doses of a study medicine called BI 764524. All participants had diabetic retinopathy (DR) with diabetic macular ischaemia (DMI). This study also wanted to find the highest dose of BI 764524 for further studies. This was the first time that BI 764524 was given to people.
High blood sugar from diabetes can damage different parts of the body, including the eyes.
Diabetic retinopathy (DR) affects the tiny blood vessels inside the retina. The retina is the thin layer of tissue at the back of the eye that senses light and helps us to see images. DR can lead to vision impairment or blindness.
Over time, when the blood supply to the retina is reduced due to damage, DR can worsen to a more severe type called proliferative diabetic retinopathy (PDR). PDR causes new blood vessels to form in the retina. These new blood vessels are fragile and can leak blood and fluid into the eye, making vision impairment worse.
Diabetic macular ischaemia (DMI) is a complication of DR, which happens when there is a lack of blood flow (ischaemia) to the macula. The macula is the central part of the retina that helps us have clear vision and to see fine details.
As damage to the retina gets worse, the tiny blood vessels in the macula become completely blocked. This results in the macula not getting the oxygen and nutrients it needs. This leads to worsening vision and can cause permanent vision loss.
At the time of this study, there was no approved treatment to prevent DMI or to stop DMI from getting worse in people with laser-treated PDR. BI 764524 is being developed as a potential treatment for DMI.Who took part in this study?
Adults 18 years of age or older could take part in this study if they have had laser treatment for PDR with DMI.
This study had 2 parts. Participants could only join one part of the study.
Part 1 had 12 participants. There were 6 men and 6 women. The youngest participant was 49 years old, and the oldest participant was 79 years old. The average age was 62 years.
Part 2 had 31 participants. There were 16 men and 15 women. The youngest participant was 25 years old, and the oldest participant was 81 years old. The average age was 60 years.How was this study done?
Part 1:
This part of the study tested 3 different doses of BI 764524. The first participants who started the study received a low dose. Participants who started the study later received higher doses of BI 764524 if the lower doses were well tolerated. On Day 1 of the study, participants received a single dose of BI 764524 as 1 injection into 1 eye, also called the study eye. The participants were divided into 3 groups. The groups were:
Low-dose group: Participants received a low dose of BI 764524 as an injection.
Medium-dose group: Participants received a medium dose of BI 764524 as an injection.
High-dose group: Participants received a high dose of BI 764524 as an injection.
The participants and doctors knew which dose each participant was receiving.
Part 1 had to finish first before Part 2 started. If participants in Part 1 could tolerate the high dose of BI 764524, this dose was chosen to be given to participants in Part 2.
Part 2:
This part of the study compared BI 764524 with sham injections.
A sham injection mimics and feels like a real eye injection, but it did not penetrate the eye. Sham did not contain any medicine. We compared BI 764524 with sham to find out how well BI 764524 works.
Participants were divided into 2 groups randomly. For every 2 participants that were assigned to the BI 764524 group, 1 participant was assigned to the sham group. No one could choose which group a participant was placed in, because it was done by a computer. The groups were:
BI 764524 group: Participants received 3 injections of high dose BI 764524. They got each injection separately into the study eye every 4 weeks for 3 months.
Sham group: Participants received 3 sham injections. They got each sham injection separately on the study eye every 4 weeks for 3 months.
Only the person giving the injection at the study site knew which treatment the participants received. The person giving the injection was not involved in any other aspect of the study. The participants and doctors did not know which treatment the participants received. This is because knowing which treatment a participant gets might affect the results of the study. At the end of the study, researchers learned which treatment each participant received.
In this study, we wanted to find out if participants could tolerate different doses of BI 764524. We also wanted to find the highest dose of BI 764524 for further studies. To find out, we looked at the following results of participants:
Part 1: The number of participants with a dose-limiting event (DLE) within 7 days of treatment with BI 764524 A DLE is when participants have certain severe health problems in the study eye that happened within 7 days of treatment with BI 764524. A DLE would limit any further increase in the dose.
Part 1 and Part 2: The number of participants with unwanted effects during each part of the study Unwanted effects are health problems that the doctors think may be caused by the study medicine.
After treatment with BI 764524, participants had follow-up visits. Participants visited the doctors regularly. During these visits, the doctors collected information about the participants’ health.
Participants in Part 1 were in the study for up to about 5 months. Participants in Part 2 were in the study for up to about 7 months.What were the results of this study?
All tested doses of BI 764524 were well tolerated by the participants.
After reviewing the study data, a scientific committee decided that the high dose should be used for further studies with BI 764524.
In Part 1:
No participant had a DLE within 7 days of treatment with BI 764524.
No participant had unwanted effects during the study.
In Part 2:
The list below shows the number of participants who had unwanted effects during the study. These are health problems that the doctors think may be caused by the study medicine.
2 out of 21 participants (10%) in the BI 764524 group had unwanted effects. The unwanted effects were: high levels of a liver enzyme in the blood (GGT increased) and floating vision spots in the gel of the eye (vitreous floaters).
0 out of 10 participants (0%) in the sham group had unwanted effects.
None of the unwanted effects were serious. This means that the unwanted effects did not lead to a hospital stay, that they were not life-threatening, and that they did not lead to a disability.Where did the study take place?
The following listing shows the countries with the number of participants per country:
United Kingdom (17)
United States of America (26)Is there more information about this study?
You can find further information about this study at these websites:
1. Go to https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2Fctr-search&data=05%7C02%7Coxfordb.rec%40hra.nhs.uk%7Caa2963ef5164499f814f08dc855d18a5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638531882096934466%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=EiQLNfSo03q6Q7r7pUM1B5KsnkWEFQG7o7t7iE%2BCZ44%3D&reserved=0 and search for the EudraCT number 2019-004432-28.
2. Go to https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Coxfordb.rec%40hra.nhs.uk%7Caa2963ef5164499f814f08dc855d18a5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638531882096943459%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=0Nw7Ki%2FHI68g9tp6W30lNFVePHWB5ZXgMbUvHxZq2DM%3D&reserved=0 and search for the NCT number NCT04424290.
Boehringer Ingelheim sponsored this study. For contact details, please visit https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.boehringer-ingelheim.com%2Fcontact-us&data=05%7C02%7Coxfordb.rec%40hra.nhs.uk%7Caa2963ef5164499f814f08dc855d18a5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638531882096948447%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=Z2leOxmqCmBjZ8ZYrUvzD%2F2m2p6jQx1omzpPDsYnPxU%3D&reserved=0.
The full title of the study is: 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 ischaemia (DMI) – the HORNBILL Study This was a Phase 1/2a study. This study started in July 2020 and finished in April 2023.REC name
South Central - Oxford B Research Ethics Committee
REC reference
20/SC/0108
Date of REC Opinion
15 May 2020
REC opinion
Further Information Favourable Opinion