Phase IIa Study Evaluating AZD7798 in Crohn's Disease

Phase 2

Recruiting

• Conditions: Moderate to Severe Crohn's Disease
• Interventions: Other: Placebo; Drug: AZD7798

• Registration Number: NCT06450197
• Lead Sponsor: AstraZeneca

Brief Summary

This is a randomised, double-blind, parallel group, placebo-controlled Phase IIa study designed to evaluate the efficacy and safety of AZD7798 in participants with moderate to severe Crohn's disease.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-05-08
• Study First Submitted QC: 2024-06-04
• Study First Posted: 2024-06-10
• Study Start: 2024-08-28
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26
• Primary Completion: 2026-04-06
• Study Completion: 2027-05-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 192

Inclusion Criteria

1. 18 to 80 years of age.

2. Diagnosis of Crohn's disease established with verifiable clinical, imaging, endoscopic and/or histopathologic evidence.

3. Moderate to severe active Crohn's disease.

4. Ileal/ileocecal (L1), colonic (L2), or ileocolonic (L3) disease, as classified based on the localisation of active inflammation.

5. Capable of giving signed informed consent.

6. A history of at least one of:

   1. Intolerance or inadequate response to conventional treatment (oral corticosteroid, azathioprine, 6-mercaptopurine, or methotrexate), biologics, or other approved advanced therapy (eg, JAK inhibitors) OR
   2. Corticosteroid dependency (defined as inability to taper below budesonide 6 mg/day or prednisolone 10 mg/day without recurrent active disease) for the treatment of Crohn's disease.

Exclusion Criteria

1. Evidence, or clinical suspicion, of other forms of IBD or concomitant additional active gastrointestinal luminal inflammatory diseases.

2. Known symptomatic strictures or bowel stenoses or strictures preventing passage of endoscope throughout the colon.

3. Any complications of Crohn's disease where surgery is anticipated or planned prior to end of study treatment.

4. Evidence of extensive prior gastrointestinal surgical interventions.

5. Within 3 months prior to screening endoscopy visit:

   1. History of toxic megacolon
   2. Diagnosis of peritonitis or need for treatment of peritonitis
   3. Bowel perforation or evidence of obstruction.

6. Undrained fistula or abscess, including intrabdominal abscesses.

7. Ongoing or expected nutritional dependency on total enteral or parenteral nutrition during study.

8. Evidence of an increased risk of colorectal cancer.

9. Symptomatic oral Crohn's disease within one year.

10. Any of the following treatments within the specified time period prior to screening endoscopy visit

    1. An anti-TNF biologic within 8 weeks prior to screening endoscopy visit
    2. Any biologic targeting immune response other than an anti-TNF within 12 weeks prior to screening endoscopy visit
    3. Other advanced small molecule treatments for Crohn's disease within 4 weeks prior to screening endoscopy visit
    4. Cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, or tacrolimus (FK-506) within 4 weeks prior to screening endoscopy visit
    5. Treatment with apheresis within 4 weeks prior to screening endoscopy visit
    6. Administration of any live vaccine within 4 weeks prior to screening endoscopy visit to end of study
    7. Faecal microbiota transplantation within 4 weeks prior to screening endoscopy visit
    8. Lymphocyte-depleting treatment within 12 months prior to screening endoscopy visit
    9. Any previous exposure to AZD7798.

11. Any changes in dosing of the following medications prior to screening endoscopy visit as outlined:

    1. 5-aminosalicylates within 2 weeks
    2. Oral corticosteroids within 2 weeks:

    (i) Prednisolone (ii) Budesonide (c) Immunomodulators within 4 weeks (d) Antibiotic therapy for the treatment of Crohn's disease (e) Probiotics within 2 weeks.

12. Known or suspected history of chronic use of nonsteroidal anti-inflammatory drugs.

13. Evidence of recent or currently active infection, including use of IV or oral antibiotics for documented infection within 30 days prior to screening endoscopy visit.

14. Evidence of chronic HBV or HCV.

15. History of TB (active or latent) unless an appropriate course of treatment has been completed.

16. Positive diagnostic TB test at screening.

17. History of serious opportunistic infection within 12 months prior to screening endoscopy visit.

18. CMV colitis within previous 12 months prior to screening endoscopy visit.

19. Positive C. difficile toxin stool test at screening.

20. Symptomatic herpes zoster infection within 3 months prior to screening endoscopy.

21. Any identified immunodeficiency.

22. Abnormal laboratory results at screening suggesting participation may be unsafe, which will prevent the patient from completing the study, or will interfere with the interpretation of the study results.

23. Reproduction:

    1. Pregnant and breastfeeding patients, or those planning to breastfeed during the study
    2. FOCBP unless completely abstinent or using a highly effective contraception and barrier method of contraception.

24. Prolonged QTcF interval.

25. Clinically significant cardiovascular conditions.

26. Current malignancy or history of malignancy.

27. Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, haematological disease, hepatic disease, renal disease, gastrointestinal disease or other major disease other than active Crohn's disease.

28. Current enrolment in another interventional study or treatment with any investigational drug within 4 months prior to screening endoscopy visit.

29. Unstable lifestyle factors.

30. Patients committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
AZD7798	AZD7798	AZD7798

Primary Outcome Measures

Name	Time	Method
CDAI remission	Week 12	Crohn's Disease Activity Index (CDAI) is a research tool used to quantify the symptoms of patients with Crohn's disease. It is based on: number of loose stools, abdominal pain, general well-being, extraintestinal complications, antidiarrheal agents used in the previous 7 days, abdominal mass felt on palpation, hematocrit and body weight

Secondary Outcome Measures

Name	Time	Method
Symptomatic remission	Week 12	Decrease of average daily stool frequency and average daily abdominal pain
Endoscopic response	Week 12	Simple Endoscopic Score for Crohn's Disease (SES-CD) is based on the evaluation of five defined bowel segments (rectum, sigmoid + descending colon, transverse colon, ascending colon, and terminal ileum), and in these segments the presence and size of ulcerations and the extent of the inflammatory area and stenosis are assessed
Endoscopic remission	Week 12	Simple Endoscopic Score for Crohn's Disease (SES-CD) is based on the evaluation of five defined bowel segments (rectum, sigmoid + descending colon, transverse colon, ascending colon, and terminal ileum), and in these segments the presence and size of ulcerations and the extent of the inflammatory area and stenosis are assessed
Endoscopic score change from baseline	Week 12	Simple Endoscopic Score for Crohn's Disease (SES-CD) is based on the evaluation of five defined bowel segments (rectum, sigmoid + descending colon, transverse colon, ascending colon, and terminal ileum), and in these segments the presence and size of ulcerations and the extent of the inflammatory area and stenosis are assessed
CDAI response	Week 12	Crohn's Disease Activity Index (CDAI) is a research tool used to quantify the symptoms of patients with Crohn's disease. It is based on: number of loose stools, abdominal pain, general well-being, extraintestinal complications, antidiarrheal agents used in the previous 7 days, abdominal mass felt on palpation, hematocrit and body weight
CDAI score change from baseline	Week 12	Crohn's Disease Activity Index (CDAI) is a research tool used to quantify the symptoms of patients with Crohn's disease. It is based on: number of loose stools, abdominal pain, general well-being, extraintestinal complications, antidiarrheal agents used in the previous 7 days, abdominal mass felt on palpation, hematocrit and body weight
Serum AZD7798 concentration	Up to 85 days	Serum AZD7798 concentration (PK)
Incidence of anti-drug antibody response	Up to 36 weeks	Incidence of anti-drug antibody (ADA) response - number and percentages with a positive ADA result
Titre of anti-drug antibody response	Up to 36 weeks	Titre of anti-drug antibody (ADA) response - immunogenicity titre will be summarized descriptively as a continuous variable, only for ADA positive tests

Trial Locations

Locations (1)

Research Site; 🇻🇳 Ho Chi Minh, Vietnam