What to consider when designing an IBD clinical trial

Inflammatory Bowel Disease (IBD) is a collective term for two chronic, autoimmune diseases of the gastrointestinal tract: ulcerative colitis (UC) and Crohn’s disease (CD). The FDA draft guidance documents for the development of drugs to treat Ulcerative Colitis and Crohn’s Disease (dated 2022) are helpful guides for navigating the important considerations for designing UC/CD clinical trials and the analysis of collected results.  

Participant Eligibility

When considering the eligibility criteria for such trials, participants should be enrolled based on a confirmed diagnosis and qualitative results as the disease can present very differently between people. The FDA draft guide suggests that sponsors should enrol participants across the whole range of both moderately and severely active disease categories. Some of the eligibility criteria may include: 

• Confirmed diagnosis of UC/CD based on endoscopy and histopathology findings.
  • For UC: enrolment based on values on the modified Mayo Score (mMs) and endoscopy subscore.
  • For CD: enrolment based on the Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD).
• Participants who have previously received biologic treatment and failed (considering the washout period) along with participants who have not received biologic treatment.
• Enrolment of participants from a range of different races and ethnicity to enable analysis of a diverse study population. 

Note: The onset of disease is generally between the ages of 15-30. Studies involving participants under the age of 18 will require special ethical considerations and tailored approaches to treatment and monitoring.

Potential IBD Endpoints

The FDA recommends IBD trials to be randomised, double-blind and placebo-controlled and able to demonstrate that any beneficial effects observed after short-term use can be continued over long-term administration. Two trial approaches to this are induction followed by randomised withdrawal maintenance, and treat-through design. To test efficacy over long-term administration, a controlled treatment period of at least one year is recommended. Trials are encouraged to demonstrate superiority to an approved therapy. If Sponsors are considering a non-inferiority design, an acceptable margin should be agreed upon prior to trial initiation. 

Primary Endpoints for UC

Clinical remission as defined by the mMs and other subscores including: stool frequency, rectal bleeding and centrally read endoscopy.  The readings of colonoscopies and endoscopies can also be used to determine disease progression or resolution. To avoid bias, any medical professionals who read and perform these procedures are blinded to the treatment received by the participant. 

Secondary Endpoints for UC

Clinical response as defined by a decrease from baseline on the mMs and other subscores including: stool frequency, rectal bleeding and centrally read endoscopy.  Other secondary endpoint suggestions include: corticosteroid-free remission, endoscopic improvement, endoscopic remission, and maintenance of remission. There are a range of other secondary and exploratory endpoints that can also be included in the trial design, including patient reported outcomes, however as with all components of trial design, these should be carefully implemented in a way to avoid and limit bias. 

Primary Endpoints for CD

Clinical remission as defined by the CDAI score (details for calculating this score can be found in the FDA draft guidance document). Endoscopic remission as defined by a SES-CD score, using centrally read endoscopies.

Secondary Endpoints for CD

Clinical response as defined by a decrease from baseline on the CDAI score, endoscopic response as defined as a reduction from baseline on the SES-CD, corticosteroid-free remission and maintenance of remission. Maintenance of remission should also be assessed for participants who enter the maintenance phase of the study in remission, and, at both early and late study timepoints for participants who are not re-randomised and treated continually. The FDA also recommends another secondary endpoint to be the composite endpoint of clinical remission and endoscopic remission which would assess the proportion of participants who achieved both clinical remission and endoscopic remission.

Exploratory Endpoints for CD

These may include histologic response/ remission, interim clinical assessments based on non-invasive measures, change from baseline in the SES-CD score and the impact of the drug on symptoms of CD that are not captured in the CDAI score. 

Recruitment Challenges and Methods

When conducting a trial which tests efficacy of a product over an extended period, new challenges to participant recruitment and retention can be faced. Datapharm has experience in assisting sites with recruitment, and Sponsors may want to consider the following points for addressing potential challenges in recruitment: 

• Use of advertising/awareness campaigns: through social media, AustralianClinicalTrials.com, partnering with GPs, and radio advertisements.

• Number of Sites: utilising a variety of sites in different locations to enrol a diverse study population and to ensure recruitment requirements can be met. Competitive recruitment can be a great tool for boosting recruitment timelines. 

• Engaging with Patient Support groups: to not only assist in participant recruitment but also retention. Advertising directly to the target study population can assist with recruitment numbers. 

• Engaging with study groups to improve design: by engaging with the target study population and allowing for feedback to be provided, future studies can be designed with the needs and preferences of the target population in mind. If a study is carefully designed to suit the people who will participate in it, they may be more likely to enrol in the study and complete it. 

If you want more details about running IBD clinical trials in Australia, get in touch with us today.