Phase IIa Study Evaluating AZD7798 in Crohn's Disease (AMALTHEA)

AstraZeneca

Status and phase: Enrolling; Phase 2

Conditions: Moderate to Severe Crohn's Disease

Treatments: Drug: AZD7798; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06450197

D9690C00005

Details and patient eligibility

About

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.

Enrollment: 192 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 18 to 80 years of age.

2. Diagnosis of Crohn's disease established with verifiable clinical, AND at least one of 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 equivalent dosing 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. All intrabdominal abscesses are excluded. Cutaneous and perianal/perirectal abscesses and fistulae are excluded unless adequately drained at least 4 weeks prior to screening endoscopy visit with no anticipation for surgery prior to end of study treatment.

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 or stable doses of steroids exceeding the following dose equivalents:

    (i) Systemic steroids > 20 mg/day or prednisolone equivalent (ii) Locally targeted steroids exceeding maximum budesonide dose equivalent (9 mg/day) (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.

31. Investigator concerns regarding patient's willingness and ability to attend all study visits, comply with the study procedures, read in order to complete questionnaires, or to complete the study period

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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192 participants in 2 patient groups, including a placebo group

AZD7798

Experimental group

Description:

AZD7798

Treatment:

Drug: AZD7798

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Other: Placebo