1366-0022 BI 685509 Non-Diabetic KD
Research type
Research Study
Full title
Randomised, double-blind (within dose groups), placebo-controlled and parallel group trial to investigate the effects of different doses of oral BI 685509 given over 20 weeks on UACR reduction in patients with non-diabetic kidney disease.
IRAS ID
293305
Contact name
Manish Saxena
Contact email
Sponsor organisation
Boehringer Ingelheim Limited
Eudract number
2020-002930-33
Duration of Study in the UK
1 years, 3 months, 29 days
Research summary
This study is a randomised, double-blind (within dose groups), placebo-controlled and parallel group trial to investigate the efficacy, safety, tolerability and Pharmacokinetics (PK) and Pharmacodynamics (PD) of 3 oral doses of BI685509 over 20 weeks of treatment in male and female patients with Chronic Kidney Disease (CKD) who are treated with either Angiotensin Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARB) treatment plus local standard of care according to local guidelines. There will a total of 240 patients randomised globally.
Eligible patients will be randomised equally into one of three parallel dose groups, and in each dose group, to treatment either with BI 685509 or matching placebo in a 3:1 ratio. All patients will start on 1 mg TID BI 685509 or matching placebo. Dose groups are as follows: Dose group 1:1mg TID; Dose group 2:2mg TID; Dose group 3:3mg TID. Each dose will be taken three times a day for approximately 20 weeks. Patients participation will last approximately 28 weeks and require approximately 15 visits in a combination of investigational site, patient's home and telephone contact. A patient will undergo physical examinations,ECGs,10 hour urine samples to measure Urine Albumin Creatinine Ratio (UACR), Mitra microsampling at clinic and home and various blood tests. Participants will also be required to keep 2 diaries - Daily Diary for Trial Drug Intake and The Diary for Urine and Blood Collection.
The main objectives of the trial are to demonstrate the effectiveness of BI 685509 and to characterise the dose response relationship for BI 685509 in patients with CKD by assessing 3 doses and placebo. The primary endpoint will be to look at the change in UACR measured in the 10 hour urine, after 20 weeks of treatment.Summary of study results:
A study to test the effect of different doses of avenciguat on kidney function in people with chronic kidney disease
This is a summary of results from 1 clinical study.
We thank all study participants. You helped us answer important questions about avenciguat (also known as BI 685509) and the treatment of chronic kidney disease (also called CKD).What was this study about?
The purpose of this study was to find out whether different doses of a medicine called avenciguat can help people with CKD.
In CKD, the function of the kidneys gets worse over time. People with CKD might eventually need to have dialysis or a kidney transplant. They also have a higher risk of getting cardiovascular diseases, such as stroke.
Avenciguat is being studied as a potential add-on treatment for CKD.Who took part in this study?
People could take part in this study if they:
- were at least 18 years old.
- had CKD that was not caused by diabetes.
A total of 261 participants took part in this study, and 259 participants received at least 1 dose of the study treatment.
There were 181 men and 80 women. The youngest participant was 21 years old, and the oldest participant was 93 years old.
The average age was 58 years.How was this study done?
Part 1:
In this study, the participants were divided into 3 groups randomly. Every participant had an equal chance of being in each group. No one could choose which group a participant was placed in, because it was done by a computer. The groups were:
- Low-dose Group: participants took a low dose of avenciguat or placebo 3 times daily for 20 weeks.
- Medium-dose Group: participants took a low dose of avenciguat or placebo 3 times daily for 2 weeks. After that, participants took a medium dose of avenciguat or placebo 3 times daily for 18 weeks.
- High-dose Group: participants took a low dose of avenciguat or placebo 3 times daily for 2 weeks. After 2 weeks, participants took a medium dose of avenciguat or placebo 3 times daily for another 2 weeks. After that, participants took a high dose of avenciguat or placebo 3 times daily for 16 weeks.
Placebo looked like avenciguat but did not contain any medicine. We compared avenciguat with placebo to find out how well avenciguat can improve the kidney function. For every 4 participants in each group, 3 had a chance to take avenciguat, and 1 had a chance to take placebo.
The participants and doctors did not know whether the participants took avenciguat or placebo. This is because knowing which treatment a participant gets might affect the results of the study. At the end of the study, participants, study doctors, and researchers learned which treatment each participant took.
Participants were in the study for about 7 months.
We wanted to find out whether avenciguat can improve the kidney function of participants with CKD. For this, we measured the level of urinary albumin creatinine ratio (also called UACR) in the participants’ urine. We then compared the UACR levels before and after 20 weeks of treatment.
Participants visited the doctors regularly. During these visits, the doctors collected information about the participants’ health.What were the results of this study?
After 20 weeks of treatment, participants in the avenciguat dose groups had a greater reduction in UACR compared to participants in the placebo group.
We did statistical tests on the results. We found that it was unlikely that the differences between each avenciguat dose group and the placebo group were due to chance.
These results showed that avenciguat may help improve the kidney function of people with CKD that was not caused by diabetes.Did participants have any unwanted effects?
Yes, participants in all groups had unwanted effects. Unwanted effects are health problems that the doctors think were caused by the study medicine.
In this study,
- 7 out of 64 participants (11%) who took avenciguat in the low-dose group had unwanted effects.
- 6 out of 65 participants (9%) who took avenciguat in the medium-dose group had unwanted effects.
- 22 out of 66 participants (33%) who took avenciguat in the high-dose group had unwanted effects.
- 14 out of 64 participants (22%) who took placebo had unwanted effects
The listing below shows the most common unwanted effects in the study. The listing also shows how many participants in each group had each of these unwanted effects
Headache:
- Low-dose Group (64 participants): 1 participant (2%)
- Medium-dose Group (65 participants): 1 participant (2%)
- High-dose Group (66 participants): 3 participants (5%)
- Placebo (64 participants): 1 participant (2%)
Swelling of the ankles, feet, or hands (peripheral oedema):
- Low-dose Group (64 participants): 0 participants (0%)
- Medium-dose Group (65 participants): 0 participants (0%)
- High-dose Group (66 participants): 3 participants (5%)
- Placebo (64 participants): 1 participant (2%)
Low blood pressure (hypotension):
- Low-dose Group (64 participants): 2 participants (3%)
- Medium-dose Group (65 participants): 2 participants (3%)
- High-dose Group (66 participants): 2 participants (3%)
- Placebo (64 participants): 3 participants (5%)
Some unwanted effects in this study were serious because they required a stay in hospital or a longer stay in hospital or were life-threatening. Unwanted effects were also serious if the doctor thought they were serious for any other reason.
In this study,
- 1 out of 64 participants (2%) who took avenciguat in the low-dose group had serious unwanted effects of stroke (cerebrovascular accident) and low blood pressure (hypotension).
- 1 out of 65 participants (2%) who took avenciguat in the medium-dose group had a serious unwanted effect of a condition wherein the body tends to bleed or bruise easily (haemorrhagic diathesis).
- No participants who took avenciguat in the high-dose group had a serious unwanted effect.
- 1 out of 64 participants (2%) who took placebo had a serious unwanted effect of a sudden kidney problem (acute kidney injury).Where did the study take place?
The following listing shows the regions and countries with the number of participants:
Asia (61): China (9), Hong Kong (8), Japan (31), Malaysia (8), and Russia (5)
Europe (80): Denmark (18), Germany (5), Poland (12), Portugal (12), Spain (24), Sweden (3), and United Kingdom (6)
Latin America (26): Argentina (26)
North America (71): Canada (7), Mexico (17), and United States (47)
Oceania (23): Australia (18) and New Zealand (5)
The total number of participants in the European Union was 74.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.mystudywindow.com%2F&data=05%7C02%7Clondonsoutheast.rec%40hra.nhs.uk%7C263d82bdf0b347cf29c708dce2ed54f2%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638634756158032160%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=HMNNLRxoFEHSjOqpjg322uFyxGF0vTAyg4B8wdi9EF0%3D&reserved=0 and search for the study number 1366-0022.
2. Go to https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2Fctr-search&data=05%7C02%7Clondonsoutheast.rec%40hra.nhs.uk%7C263d82bdf0b347cf29c708dce2ed54f2%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638634756158050448%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=f922dBtl1NDuwyYXmUHxm9WwYXvfsidTCbforU8RIVo%3D&reserved=0 and search for the EudraCT number 2020-002930-33.
3. Go to https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Clondonsoutheast.rec%40hra.nhs.uk%7C263d82bdf0b347cf29c708dce2ed54f2%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638634756158064383%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=wwunsppXGGE76Dd1VaV2uE%2BZ0S8AP9PpcEf8D7f6sk4%3D&reserved=0 and search for the NCT number NCT04736628.
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%7Clondonsoutheast.rec%40hra.nhs.uk%7C263d82bdf0b347cf29c708dce2ed54f2%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638634756158082276%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=2u0blpMiAM7O9y0u57UYfgLAdonHiF%2F5d%2B0J8iCdTFY%3D&reserved=0.
The full title of the study is: Randomised, double-blind (within dose groups), placebo-controlled and parallel group trial to investigate the effects of different doses of oral BI 685509 given over 20 weeks on UACR reduction in patients with non-diabetic kidney disease
This was a Phase 2 study. This study started in May 2021 and finished in September 2023.Are there additional studies?
If we do more clinical studies with avenciguat, you will find them on the websites listed above. To search for these studies, use the words avenciguat and BI 685509.Important notice
This lay summary is provided as part of Boehringer Ingelheim’s commitment to publicly share clinical study results.
This summary shows only the results from one study and may not represent all of the knowledge about the medicine studied. Other studies may have different results. Usually, more than one study is carried out to find out how well a medicine works and to determine the side effects of a medicine.
This lay summary may include uses, formulations, or treatment regimens for the medicine studied that may be approved or not approved in your country. This lay summary is not intended to promote any product or indication, to guide treatment decisions, or to replace the advice of a healthcare professional.
You should not change your therapy based on the results of this study. Always consult with your treating physician about your therapy.
©2024 Boehringer Ingelheim International GmbHREC name
London - South East Research Ethics Committee
REC reference
21/LO/0194
Date of REC Opinion
20 Apr 2021
REC opinion
Further Information Favourable Opinion