Phase IIa Study Evaluating AZD7798 in Crohn's Disease

Moderate to Severe Crohn's Disease Clinical Trial

— AMALTHEA  

Official title:

A Double-blind, Placebo-controlled Phase IIa Study to Evaluate the Efficacy and Safety of AZD7798 in Patients With Moderate to Severe Crohn's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06450197
• Other study ID #: D9690C00005
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 17, 2024
• Est. completion date: May 21, 2027

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 192
• Est. completion date: May 21, 2027
• Est. primary completion date: April 6, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease
• Moderate to Severe Crohn's Disease

Intervention

Drug:
• AZD7798
AZD7798

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Australia	Research Site	South Brisbane
Austria	Research Site	Klagenfurt am Wörthersee
Brazil	Research Site	Campinas
Brazil	Research Site	Curitiba
Brazil	Research Site	Jaú
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Santo Andre
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Talcahuano
Chile	Research Site	Viña del Mar
Germany	Research Site	Berlin
Germany	Research Site	Kiel
Germany	Research Site	Ulm
Italy	Research Site	Milano
Japan	Research Site	Chiba-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Kashiwa-shi
Japan	Research Site	Kure-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Shinjuku-ku
Malaysia	Research Site	Johor Bahru
Malaysia	Research Site	Kota Bharu
Malaysia	Research Site	Kota Kinabalu
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuching
Mexico	Research Site	Mexico City
Romania	Research Site	Bucharest
Romania	Research Site	Cluj Napoca
Romania	Research Site	Timisoara
Slovakia	Research Site	Kosice
Slovakia	Research Site	Nitra
Slovakia	Research Site	Presov
Slovakia	Research Site	Trnava
South Africa	Research Site	Cape Town
South Africa	Research Site	Milnerton
South Africa	Research Site	Plumstead
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
Sweden	Research Site	Linköping
Sweden	Research Site	Stockholm
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	New Taipei City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Bursa
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Izmit
Turkey	Research Site	Malatya
Ukraine	Research Site	Chernivts?
Ukraine	Research Site	Kiev
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Ternopil
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Vinnytsia
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Chesterfield	Michigan
United States	Research Site	Garland	Texas
United States	Research Site	San Antonio	Texas
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh city

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Chile,  Germany,  Italy,  Japan,  Malaysia,  Mexico,  Romania,  Slovakia,  South Africa,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CDAI remission	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	Week 12
Secondary	Endoscopic response	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	Week 12
Secondary	Endoscopic remission	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	Week 12
Secondary	Endoscopic score change from baseline	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	Week 12
Secondary	CDAI response	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	Week 12
Secondary	CDAI score change from baseline	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	Week 12
Secondary	Symptomatic remission	Decrease of average daily stool frequency and average daily abdominal pain	Week 12
Secondary	Serum AZD7798 concentration	Serum AZD7798 concentration (PK)	Up to 85 days
Secondary	Incidence of anti-drug antibody response	Incidence of anti-drug antibody (ADA) response - number and percentages with a positive ADA result	Up to 36 weeks
Secondary	Titre of anti-drug antibody response	Titre of anti-drug antibody (ADA) response - immunogenicity titre will be summarized descriptively as a continuous variable, only for ADA positive tests	Up to 36 weeks