Efficacy, Safety, and Tolerability of Bepranemab (UCB0107)
Research type
Research Study
Full title
A Patient- and Investigator-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Study Participants With Prodromal to Mild Alzheimer’s Disease (AD), Followed by an Open-Label Extension Period
IRAS ID
299120
Contact name
Christopher Kipps
Contact email
Sponsor organisation
UCB Biopharma SRL
Eudract number
2020-005829-88
Duration of Study in the UK
4 years, 0 months, 1 days
Research summary
Summary of Research:
The study is being performed in participants with early signs (prodromal signs) of Alzheimer’s disease (AD) or have a diagnosis of mild AD. This study is being developed to investigate the effect of bepranemab the study drug vs placebo on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), a scale used to quantify the severity of symptoms of dementia, as the change from Baseline to Week 80 in the CDR-SB total score, in study participants with prodromal to mild AD.\nThis study will involve a total of 450 study participants across approximately 125 centres in about 10 countries throughout Europe and North America.\nThe study typically consists of a Screening Period (up to 60 days) and then a Double-blind Treatment Period of 80 weeks (18 months). If the participant decides to stop their participation at the end of these 80 weeks, they will be followed up for another 16 weeks of Safety Follow-up Period.\nThere is an option for the participant to continue receiving the study drug and will then enter the Open-label Extension (OLE) Treatment Period. The participants study doctor will discuss this with participants and confirm their eligibility to take part in this open label study. The OLE Period then continues with 44 weeks of treatment to Week 124. Once the treatment period has ended, the participant will enter the Safety Follow-up Period and have the first visit 4 weeks later at Week 128, the Safety Follow-up Period lasting up to 20 weeks. \nIn total the duration is up to approximately 152 weeks (almost 3 years).\n\n\nSummary of Results:
For full lay persons summary of results please go the below website:
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Feuclinicaltrials.eu%252Fctis-public%252Fview%252F2023-506170-12-00%2FNBTI%2FJVnHAQ%2FAQ%2F7acf672d-af59-47b4-9ebf-2734e7807dc0%2F1%2FdnNDrCleHy&data=05%7C02%7Coxfordb.rec%40hra.nhs.uk%7C56de579ec8864a76019608def91eef72%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639222108430572904%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=OOVs8MO50fWx9WZ6pxKQ5iPcJ7YPcVnnFApg99seeRo%3D&reserved=0Please follow these steps
1. Select “Trial Results” tab
2. Select “Layperson Summary of Results”
3. Select “AH0003-lay-persons-summary-of-results-public” EnglishBRIEF OVERVIEW FROM LAY PERSONS SUMMARY OF RESULTS
Thank you
UCB thanks all the participants and caregivers of this study. All the participants helped the researchers learn more about using bepranemab in people with early Alzheimer’s disease
(AD). Bepranemab is also called UCB0107.Why was the research needed?
Researchers are looking for a different way to treat AD. Before a drug is available for all patients, researchers do clinical studies to find out how the drug works and how safe it is.What treatments did the participants receive?
This study had 2 parts. In Part 1, the participants in this study received bepranemab or a placebo. In Part 2, participants took 1 of 2 doses of bepranemab.What were the results of the study?
The main questions the researchers wanted to answer in this study were:
- Did bepranemab help to slow the progression of the participants’ disease?
Overall, the researchers found that bepranemab did not slow the progression of the participants’ disease compared to the placebo.
- What other effects did bepranemab have in participants?
Overall, the researchers found that bepranemab helped to slow the decline of memory and thinking ability better than the placebo. But, bepranemab did not help to slow the decline of the participants’ ability to perform daily activities compared to the placebo. The researchers also found that participants who had low levels of abnormal tau protein in the brain when they joined the study tended to have a better response to bepranemab.What medical problems did the doctors report as possibly related to study treatment?
-In Part 1, participants received either bepranemab or the placebo. Overall, 14.2% of the participants in Part 1 (66 out of 464) had medical problems that the study doctors reported as possibly related to study treatment.
-In Part 2 of the study, all participants received bepranemab. Overall, 6.5% of the participants in Part 2 (25 out of 387) had medical problems that the study doctors reported as possibly related to study treatment.
-In both parts, the most common possibly related medical problem was headache. The number of participants who had a headache that was possibly related to study treatment was similar for participants who received bepranemab and participants who received the placebo.Why was the research needed?
Before a treatment is available to the public, researchers do clinical studies to get information about how well the treatment works and about how safe it is.
The researchers in this study wanted to learn if bepranemab slowed disease progression in a small number of participants with early Alzheimer’s disease. They also wanted to learn if the participants had any medical problems during the study.
Alzheimer’s disease (AD) is the most common type of dementia. In people with AD, cells in the brain die over time. This can lead to memory loss, difficulty speaking, difficulty thinking, and difficulty performing daily tasks.
AD has several stages. The earliest stages where symptoms are seen are known as prodromal AD and mild AD. Prodromal AD is also known as mild cognitive impairment. People with prodromal AD may have mild memory loss but can perform most of their daily tasks. People with mild AD have more significant memory loss and may need help performing some daily tasks. The participants in this study had either prodromal or mild AD.
One way that AD may cause brain cells to die is through abnormal forms of a protein called tau that can spread in the brain. The study drug bepranemab is designed to work by blocking abnormal tau from spreading and causing damage to brain cells. Researchers think that receiving bepranemab when AD is at its early stages could help to delay the progression of the disease in later stages.What were the main questions studied?
The main questions the researchers wanted to answer in this study were:
● Did bepranemab help to slow the progression of the participants’ disease?
● What other effects did bepranemab have in participants? The researchers also wanted to know what medical problems happened that were possibly related to study treatmentWho participated in the study?
There were 466 participants with early AD who participated in this study. They were 50 to 80 years old when they joined. The study included participants in 10 countries.
In this study, the researchers included participants with prodromal or mild AD who:
● Had their AD diagnosis confirmed by scans of the brain along with other signs and symptoms of AD
● Had a caregiver, such as a family member, who was in regular contact with the participant and who could help answer questions about the participant’s symptoms
● Did not have any other conditions besides AD that might affect their memory and thinking ability
Each participant who completed the study was in the study for up to a little more than 3 years. The whole study lasted a little more than 4 years. The study started in June 2021 and ended in August 2025.What were the results of the study?
This is a summary of the main results from this study. These are the results from all the
participants combined. The individual results of each participant might be different and
are not in this summary.Did bepranemab help to slow the progression of the participants’ disease?
No. In this study, the researchers could not conclude that the participants who received bepranemab had slower progression of their disease compared to the participants who received the placebo.
To answer this question, the study doctors used a scale called the Clinical Dementia Rating Sum of Boxes (CDR-SB). At different times throughout the study, the study doctors used CDR-SB total scores to keep track of how severe the participants’ dementia symptoms were. These symptoms included the loss of memory, the ability to solve problems, and the ability to do personal care. Higher CDR-SB total scores mean that the dementia symptoms were more severe.
The researchers calculated the change in the CDR-SB total score from before treatment to after 80 weeks of treatment. This is called the change from baseline. A positive number for the change from baseline in the CDR-SB total score means that the dementia symptoms were more severe after 80 weeks of treatment than before treatment.
The results for the change from baseline in the CDR-SB total scores after 80 weeks of treatment are shown below:
● The participants who received the placebo had their CDR-SB total scores increase by 1.8 on average.
● The participants who received 45 mg/kg of bepranemab had their CDR-SB total scores increase by 1.9 on average.
● The participants who received 90 mg/kg of bepranemab had their CDR-SB total scores increase by 2.2 on average.
These results mean that the participants who received either dose of bepranemab did not have a slower decline in their dementia symptoms compared to the participants who received the placebo.What other effects did bepranemab have in participants?
Overall, the researchers found that bepranemab helped to slow the decline of memory and thinking ability better than the placebo. But, bepranemab did not help to slow the decline of the participants’ ability to perform daily activities compared to the placebo.
To answer this question, the researchers kept track of changes in the participants’ memory and thinking and their ability to perform daily activities. The researchers also used brain scans to measure the amount of abnormal tau protein in the brain at different times during the study.
Overall, the researchers found that:
● Participants who had low levels of abnormal tau in the brain when they joined the study tended to have a better response to treatment with bepranemab.
● Participants who received bepranemab had smaller increases of abnormal tau in their brain compared to participants who received the placebo.
● Participants who received bepranemab had a slower decline in their memory and thinking ability compared to participants who received the placebo.
● Participants who received bepranemab and participants who received the placebo had a similar ability to perform daily activities.
More research will be needed to confirm these results.What medical problems did the study doctors report as possibly related to study treatment?
Medical problems that the participants had during the study that the doctors reported as possibly related to study treatment are called “adverse reactions”.
In this study, the doctors did not know what the participants were receiving when the medical problems happened. The study doctors reported the medical problems they thought were caused by bepranemab, even though the participants could have received the placebo. So, some adverse reactions may be reported in participants who received the placebo, even though the placebo does not directly cause medical problems.
Overall, 14.2% of the participants (66 out of 464) had an adverse reaction in Part 1 of this
study. The most common adverse reaction in Part 1 was headache.
Overall, 6.5% of the participants (25 out of 387) had an adverse reaction in Part 2 of this study. The most common adverse reaction in Part 2 was headache.What did the researchers learn from this study?
The results of this study have helped researchers learn more about using bepranemab in people living with early Alzheimer’s disease. In this study, the researchers found that:
- Receiving bepranemab for 80 weeks did not help to slow the participants’ disease progression compared to the placebo as measured by the CDR-SB total score.
- Overall, the researchers found that bepranemab helped to slow the decline of memory and thinking ability better than the placebo. But, bepranemab did not help to slow the decline of the participants’ ability to perform daily activities compared to the placebo.
● The researchers also found that participants who had low levels of abnormal tau protein in the brain when they joined the study tended to have a better response to bepranemab.
● In Part 1, 14.2% of the participants (66 out of 464) had an adverse reaction.
● In Part 2, 6.5% of the participants (25 out of 387) had an adverse reaction.
● 461 out of 464 participants (99%) were able to receive study treatment without serious adverse reactions.
● 5 out of 464 participants (1%) stopped receiving study treatment in either Part 1 or Part 2 because of adverse reactions.
● The most common adverse reaction was headache in both treatment groups.
Deciding which treatments work best for patients almost always takes results from several studies. This summary shows only the main results from this one study. Other studies may provide new information or different results.Where can I learn more about this study?
You can find more information about this study on the websites listed below:
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2Fct2%2Fshow%2Fstudy%2FNCT04867616&data=05%7C02%7Coxfordb.rec%40hra.nhs.uk%7C56de579ec8864a76019608def91eef72%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639222108430593782%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=wi2VN6gUUACG6AJa5GLSSeoEWpU68g4PdYTddD%2BENsk%3D&reserved=0
euclinicaltrials.eu/ctis-public/view/2023-506170-12-00REC name
South Central - Oxford B Research Ethics Committee
REC reference
21/SC/0198
Date of REC Opinion
29 Jul 2021
REC opinion
Further Information Favourable Opinion