Clinical trial NCT06681324: Study Evaluating AZD7798 for Treatment in Crohn's Disease Patients With an Ileostomy
Official title: A Participant- and Investigator-blind, Randomized, Placebo-controlled Phase II Study to Evaluate Safety, Tolerability, and Mucosal Repair With AZD7798 in Patients With Active Ileal Crohn's Disease and an Ileostomy (CALLISTO)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Crohn's disease
ileostomy
inflammation
small bowel
stoma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-11-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized 2:1 to receive either AZD7798 or placebo during 12-week participant- and Investigator- blind induction period. At week 12 after induction period, all eligible participants will enter 40-week open label maintenance period.
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate safety, tolerability, and effect on mucosal repair of AZD7798 compared with placebo in participants with active ileal Crohn's disease and an ileostomy.

Detailed description: This is a participant-and investigator-blind, randomized, parallel-group, placebo controlled phase II study designed to evaluate safety, tolerability, and mucosal repair with AZD7798 in participants with active ileal Crohn's disease and an ileostomy. This study will include a screening period, an induction period, an open-label maintenance period, and a follow-up period. Approximately 30 participants will be randomized globally to receive either AZD7798 or placebo during 12-week participant- and investigator- blind induction period. At week 12 after induction period, all eligible participants will enter 40-week open label maintenance period. Follow-up visits will take place 8 weeks and 18 weeks after the last dose of study intervention, whether this occurs during the induction period or the open-label maintenance period.

Eligibility criteria: Inclusion Criteria:

* 18 to 80 years of age.
* Diagnosis of Crohn's disease established with clinical, imaging, endoscopic, and/or histopathologic evidence.
* Ileostomy for at least 3 months.
* Prior to screening endoscopy, clinical suspicion of active ileal inflammation based on at least one of the following: previous endoscopy, imaging (CT, MRI, IUS), or FCP above upper reference limit.
* Active ileal Crohn's disease as determined by active intestinal mucosal inflammation, as demonstrated on video recorded ileoscopy performed during the screening period and scored by a blinded central reader with agreement on the SES CD ≥ 4 of the ileal segment proximal to the stoma. Participants with inflammation in additional intestinal segments are not excluded.
* Capable of giving signed informed consent.

Exclusion Criteria:

* Concomitant additional gastrointestinal luminal inflammatory diseases
* Strictures/stenoses preventing passage of endoscope throughout the specified segment
* Short bowel syndrome
* Within 3 months prior to screening:

  1. Diagnosis of peritonitis or need treatment of peritonitis
  2. Bowel perforation or evidence of obstruction
* All intrabdominal, cutaneous and perianal/perirectal abscesses and fistulae are excluded with exception of: cutaneous and perianal/perirectal abscesses which are adequately drained 4 weeks prior to randomization, and intraabdominal fistulae between bowel segments only without complications
* Ongoing or expected nutritional dependency on total enteral or parenteral nutrition during study (partial nutrition acceptable).
* In participants with any remaining colon and/or rectum, evidence of an increased risk of colorectal cancer, including:

  1. Adenomatous colonic/rectal polyps that have not been removed
  2. Intestinal dysplasia
  3. Not undertaking appropriate surveillance, if indicated, for colorectal dysplasia/malignancy
* Reversal of ileostomy or formation of J-pouch planned prior to end of study period.
* High-output stoma (eg, \> 2000 mL/24 hours) associated with volume depletion and/or electrolyte disturbance to the extent that, in the opinion of the Investigator, it may put the participant at undue risk because of participation in the study, or impact their ability to participate in the study or interfere with the interpretation of study data.
* Any of the following treatments within the specified time period:

  1. An anti-TNF biologic within 8 weeks prior to randomization
  2. Any biologic targeting immune response other than an anti-TNF (including vedolizumab and ustekinumab) within 12 weeks prior to randomization.
  3. Other advanced small molecule treatments for Crohn's disease within 4 weeks prior to randomization
  4. Cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, or tacrolimus within 4 weeks prior to randomization
  5. Treatment with apheresis (eg, Adacolumn, Cellsorba) within 4 weeks prior to randomization
  6. Administration of any live vaccine within 4 weeks prior to randomization, or planned administration of any such vaccine during the study
  7. Faecal microbiota transplantation within 4 weeks prior to randomization
  8. Regular intake of NSAIDs within 12 weeks prior to screening ileoscopy and during the study (defined as at least times per week for more than 3 months; not applicable to daily aspirin use up to 325 mg per day)
  9. Lymphocyte-depleting treatment, including, but not limited to rituximab, within 12 months prior to randomization
* Any changes in dosing of the following medications prior to screening ileoscopy as outlined

  1. 5-aminosalicylates within 2 weeks
  2. Oral corticosteroids within 2 weeks. Also excluded if on stable dosing of steroids exceeding the following dose equivalents:

  (i) Systemic steroids \> 20 mg/day prednisolone dose or equivalent (ii) Locally targeted steroids exceeding maximum budesonide dose or equivalent \[9 mg/day\] (c) Immunomodulators (thiopurines or methotrexate) within 4 weeks (d) Antibiotic therapy for the treatment of Crohn's disease, eg, ciprofloxacin or metronidazole within 2 weeks (e) Probiotics within 2 weeks
* Evidence of recent or currently active infection, including use of IV or oral antibiotics for documented infection within 30 days prior to screening.
* Evidence of chronic hepatitis B or C infection
* History of TB (active or latent) unless an appropriate course of treatment has been completed.
* Positive diagnostic TB test at screening.
* History of serious opportunistic infection within 12 months prior to screening
* Symptomatic herpes zoster infection within 3 months prior to screening.
* Positive C. difficile toxin test at screening.
* Any identified immunodeficiency
* Any other abnormal laboratory results at screening, which, in the opinion of the Investigator, will prevent the participant from completing the study or will interfere with the interpretation of the study results
* Prolonged QTcF interval \> 450 ms (or \> 480 ms for patients with bundle branch block) or congenital long-QT syndrome or family history of long-QT syndrome or sudden cardiac death in age \< 40 years.
* Clinically significant cardiovascular conditions
* Reproduction:

  1. Pregnant and breastfeeding participants, or those planning to breastfeed during the study
  2. FOCBP, unless they agree to complete abstinence or to use a highly effective contraceptive method AND barrier method
* Current malignancy or history of malignancy
* Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, haematological disease, hepatic disease including large duct primary sclerosing cholangitis with jaundice, recurrent cholangitis or cirrhosis, renal disease, gastrointestinal disease, or other major disease other than active Crohn's disease.
* Current enrolment in another interventional study or treatment with any investigational drug within 4 months (or 5 half-lives, whichever is longer) prior to screening
* Unstable lifestyle factors
* Participants committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
* Involvement in the planning and/or conduct of the study
* Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
* Previous randomization in the present study.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal Vital signs: Blood pressure
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal Vital signs: Pulse rate
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal values in haematology: complete blood count (CBC)
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal values in haematology: white blood cell (WBC) count
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal values in haematology: RBC
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal values in clinical chemistry: kidney function
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal values in clinical chemistry: electrolytes
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal values in clinical chemistry: liver function
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal values in clinical chemistry: hs-CRP
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal values in clinical chemistry: glucose
timeFrame: from Week 0 to Week 12
measure: Number of participants with abnormal values in ECG readings
timeFrame: from Week 0 to Week 12
Secondary outcomes:
measure: Difference in mean change from baseline in endoscopic score between active and placebo
timeFrame: Week 12
measure: Number of participants with endoscopic response
timeFrame: Week 12
measure: Number of participants with endoscopic remission
timeFrame: Week 12
measure: Serum AZD7798 concentration
timeFrame: up to 52 Weeks
measure: Incidence of anti-drug antibody response
timeFrame: up to 52 Weeks
measure: Titre of anti-drug antibody response
timeFrame: up to 52 Weeks
measure: Number of participants with adverse events in active treatment
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal vital signs: Blood pressure
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal vital signs: Pulse rate
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal values in haematology: complete blood count (CBC)
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal values in haematology: white blood cell (WBC) count
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal values in haematology: RBC
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal values in clinical chemistry: kidney function
timeFrame: from week 12 to week 52
measure: Number of participants with abnormal values in clinical chemistry: electrolytes
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal values in clinical chemistry: liver function
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal values in clinical chemistry: hs-CRP
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal values in clinical chemistry: glucose
timeFrame: from Week 12 to Week 52
measure: Number of participants with abnormal values in ECG readings
timeFrame: from week 12 to week 52
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Linköping
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References: