52-Week Phase 2b/3 Crohn's Disease Study
Research type
Research Study
Full title
A 52-Week, Multicenter, Randomized, Double-blind, Double-dummy, Placebo and Active-controlled, Operationally Seamless Phase 2b/3, Parallel-group Study to Assess the Efficacy and Safety of Brazikumab in Participants with Moderately to Severely Active Crohn’s Disease
IRAS ID
261470
Contact name
Nigel Trudgill
Contact email
Sponsor organisation
AstraZeneca
Eudract number
2018-004346-42
Duration of Study in the UK
3 years, 4 months, 5 days
Research summary
Research Summary
Crohn's disease (CD) is a chronic disease in which parts of the digestive system become inflamed. The most common symptoms are abdominal pain, diarrhoea, tiredness and loss of appetite. CD affects at least 115,000 people in the UK.
Current treatment options for patients with moderately to severely active CD are usually guided by severity of disease, location, and presence of additional clinical complications. Adalimumab (Humira) is currently the standard of care for these patients. Despite the availability of treatments, there is still a need for novel therapies for the treatment of CD due to the evidence that not all patients will respond or maintain their response to the available treatment options.
Brazikumab is being developed as a treatment for CD to reduce intestinal inflammation and improve signs and symptoms. The purpose of this study is to look in to the safety and effectiveness of brazikumab for the treatment of CD.
Approximately 1140 participants worldwide with moderately to severely active CD will take part. Participants will be randomised to 1 of 4 study groups if they are involved in Stage 1 (low dose brazikumab, high dose brazikumab, Humira, or placebo) or 1 of 3 study groups if they are involved in Stage 2 (low dose brazikumab, high dose brazikumab, or Humira). There will be a total of 31 separate study visits over a period of approximately 70 weeks.
Summary of Results
The trial was early terminated. Given the low participant number randomized prior to study termination it was not possible to generate meaningful results for efficacy endpoints.
The participants were in the trial for up to about 16 months. But, the entire trial took nearly 5 years to finish.
The trial started in December 2018 and ended in October 2023.
The researchers had planned for the trial to last longer. But, based on a decision by AstraZeneca AB in June 2023, this trial was stopped early, and no more participants were allowed to join any of the groups in the trial. The participants already taking part in the trial stopped receiving trial treatment, but this was not due to any safety concerns with brazikumab. The trial doctors continued to monitor these participants for a period of time after they stopped receiving trial treatment for safety reasons.Did the participants who received brazikumab have an improvement in their Crohn’s disease?
Overall, the researchers were not able to determine the answer to this question.
This is because not enough participants received trial treatment before the trial was stopped.
To try to answer this question, the researchers used a system called the Crohn’s Disease Activity Index (CDAI). The CDAI is based on several components:
X Physical examinations
X Medications that a person is using to stop diarrhea X The levels of red blood cells in the blood X Changes in body weight X Body temperature X The number of loose bowel movements a person has X The number of times a person experiences stomach pain X General well-being Researchers measure all these components to give a participant a single CDAI score. In this trial, the researchers measured the participants’ CDAI scores at the start of the trial and at different points during the trial.
The researchers recorded how many participants had a CDAI score of less than 150 after receiving trial treatment. This is called CDAI remission, and it means the participant’s Crohn’s disease had improved. The researchers planned to compare the number of participants who achieved CDAI remission in the brazikumab groups with the number of participants who achieved CDAI remission in the placebo group.
However, the researchers were not able to find out if brazikumab improved the participants’ Crohn’s disease because not enough participants received trial treatment before the trial was stopped.Did the participants who received brazikumab have fewer symptoms after receiving trial treatment for 12 weeks and for 52 weeks?
Overall, the researchers were not able to determine the answer to this question. This is because not enough participants received trial treatment before the trial was stopped.
To try to answer this question, the researchers asked the participants to answer a set of questions about their bowel movements and their Crohn’s disease symptoms each day. The responses were used to give each participant a score for how often they had:
X Loose bowel movements
X Stomach pain
The researchers measured the participants’ scores for these questions at the start of the trial and at different points during the trial. Then, they measured how many participants in each group had a loose bowel movement score of 3 or less and a stomach pain score of 1 or less. This is called clinical remission, and it means the participants had fewer symptoms.
The researchers planned to compare the number of participants who achieved clinical remission in the brazikumab groups with the number of participants who achieved clinical remission in the placebo group after receiving trial treatment for 12 weeks and for 52 weeks.
However, the researchers were not able to find out if the participants who received brazikumab had fewer symptoms because not enough participants received trial treatment before the trial was stopped.This section is a summary of the medical problems that the participants had during this trial that the doctors reported as possibly related to the trial treatments. These medical problems are called adverse reactions. An adverse reaction is considered serious when it is life-threatening, causes lasting problems, or requires hospital care. The results from several trials are needed to decide if a treatment causes an adverse reaction.
In this trial, the doctors did not know what the participants were receiving when the medical problems happened. So, some adverse reactions may be reported in participants who received the placebo, even though the placebo does not directly cause medical problems.Did any adverse reactions happen during this trial?
There were 5.8% of participants who had adverse reactions in this trial. This was 5 out of 86 participants.
The most common adverse reaction was low levels of a type of white blood cell called lymphocytes (Lymphopenia).
None of the participants had serious adverse reactions during this trial.This trial helped researchers learn more about how brazikumab affects people with Crohn’s disease.
Researchers look at the results of many trials to decide which treatments work best and are safest.REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
19/WM/0204
Date of REC Opinion
10 Sep 2019
REC opinion
Further Information Favourable Opinion