Positron Emission Tomography Study of Changes in [11C]AZ14132516 Uptake Following Administration of AZD7798 to Patients With Crohn's Disease.

A Phase Ib Open Label Positron Emission Tomography Study to Assess Changes in Intestinal [11C]AZ14132516 Uptake Following Administration of Multiple Doses of AZD7798 to Patients With Crohn's Disease.

The purpose of this study is to measure the changes in intestinal uptake of radioligand [11C]AZ14132516 following multiple doses of AZD7798 in participants with Crohn's disease.

Study Overview

• Status: Completed
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: AZD7798; Drug: [11C]AZ14132516

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 14186
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be ≥ 20 to 80 years of age, inclusive, at the time of signing the informed consent.
• Participants with confirmed Crohn's disease with small bowel involvement (Montreal terminal ileum [L1] or ileocolon [L3]) per study gastroenterologist (diagnosed via combination of clinical findings and at least one of endoscopy and/or histology and/or imaging) with diagnosis made at least 6 months before screening.

• Participants with active Crohn's disease as determined by one of the following:

  1. Evidence of active inflammation on cross-sectional imaging (CT, MRI or bowel ultrasound scan) or endoscopy within 6 months before screening OR EITHER
  2. If no cross-sectional imaging or endoscopy performed within 6 months before screening, a bowel ultrasound scan may be performed to confirm active disease OR
  3. If no cross-sectional imaging or endoscopy performed within 6 months before screening, elevated faecal calprotectin AND CRP
• Body habitus compatible with PET examination.
• Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent
• Able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures.

Exclusion Criteria:

• Other form of IBD or concomitant, additional, active GI luminal inflammatory diseases.
• CMV colitis within 12 months before screening.
• Crohn's complications including short bowel syndrome, strictures that are symptomatic or with pre-stenotic dilatation or other conditions where surgery anticipated during study period.
• Planned bowel or perianal surgery within 6 months before screening.
• Bowel resection surgery within 6 months before screening.
• Undrained fistula or abscess (including active perianal disease).
• Positive Clostridium difficile toxin test during screening.
• Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, haematological disease, hepatic disease, renal disease, GI disease, or other major diseases other than active Crohn's disease and associated extra-intestinal manifestations.
• Ongoing psychiatric conditions that in the opinion of the Investigator, precludes study participation.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to biologic therapies.
• Participants with unstable hypertension (as judged by the Investigator) or symptomatic hypotension, history of pre-syncope or syncope due to orthostatic hypotension and/or induced by change of posture.
• Significant abnormalities on clinical examination, including neurological and physical examination, vital signs, and ECG, other than signs of Crohn's disease.
• Clinical chemistry, haematology, or urine analysis results that may interfere with the study or present a safety risk to the participant.
• Abnormal vital signs, after 10 minutes of supine rest as judged by the Investigator.
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG that may interfere with the interpretation of QTc changes.
• Positive hepatitis B, hepatitis C, or HIV serology
• Treatment with an anti-TNF within 8 weeks of the first dose and throughout the study period, before the first dose and throughout study period, unless therapeutic drug monitoring is performed, and drug concentrations are undetectable.
• Treatment with any biologic, other than an anti-TNF (including vedolizumab and ustekinumab) within 12 weeks prior to first dose and throughout the study period, unless therapeutic drug monitoring is performed, and drug concentrations are undetectable.
• Treatment with rituximab within 12 months before first dose and throughout the study period.
• Treatment with Sphigosine-1-phosphate receptor modulators or Janus kinase inhibitors within 4 weeks before first dose and throughout the study period.
• Treatment with apheresis (eg, Adacolumn, Cellsorba) within 2 weeks prior to first dose and throughout the study period.
• Treatment with corticosteroids at a total daily dose of greater than 20 mg prednisone or equivalent (greater than 9 mg budesonide).
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or site staff).
• 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.
• Suffers from claustrophobia that limits the ability to undergo the scanning procedure.
• Positive SARS-CoV-2 rapid antigen test at screening.
• Any other reason that, in the study Investigator opinion, prohibits the inclusion of the participants into 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.
• Live or attenuated vaccine within 4 weeks before screening and until 12 weeks after the end of the follow-up period (1 year for Bacillus Calmette-Guérin vaccination).
• An active infection, or history of serious infection within 28 days before screening.
• History of symptomatic herpes simplex (excluding cold sores) or herpes zoster infection within 3 months prior to screening.
• Positive or indeterminate TB QuantiFERON test performed within 1 year of screening (without known interval exposure to TB) or during screening period unless evidence of completion of full treatment course for latent TB with no clinical symptoms or signs indicative of re activation.
• Chest x-ray with signs of malignancy or latent or active TB infection performed within 1 year of screening (without known interval exposure to TB) or during screening period.
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days/5 half-lives, whichever is longer, of the first administration of IMP in this study. The period of exclusion begins 30 days/5 half-lives after the final dose, whichever is longer, .

• Current malignancy or history of malignancy, except for:

  1. Basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the participant is in remission and curative therapy was completed at least 12 months prior to screening.
  2. Other non-GI malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years before screening.
• For females only: Currently pregnant (confirmed with positive pregnancy test) or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD7798; Arm consists of up to 2 panels	Drug: AZD7798; Each participating patient will receive the study drug as specified in the study protocol.; Other Names: Study Drug; Drug: [11C]AZ14132516; A single microdose (≤ 10 μg) of radiopharmaceutical [11C]AZ14132516 will be extemporaneously prepared and administered to each participant prior to each PET examination; Other Names: Radioligand

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in intestinal SUV/SUVR	Standardized uptake value (SUV) is the radioactivity concentration in given region of interest normalized for injected radioactivity and body weight. Standardised uptake value ratio (SUVR) is the ratio of SUV in a given region of interest to a reference region without significant radioligand uptake	Weeks 13, 16, 20 and 24 (may vary between participants)

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum AZD7798 concentration	Weeks 0, 4, 8, 12 (may vary between participants)
Incidence and titre of anti-drug antibodies	Week 0, 4, 8, 12 and 24 (may vary between participants)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with safety findings, AEs	Safety will be assessed by Adverse Events, vital signs, haematology and clinical chemistry	Until final follow-up, week 24 (may vary between participants)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Maria Creignou, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2024
• Primary Completion (Actual): March 27, 2026
• Study Completion (Actual): March 27, 2026

Study Registration Dates

• First Submitted: May 22, 2024
• First Submitted That Met QC Criteria: May 22, 2024
• First Posted (Actual): May 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Radioisotope; Diagnostic Techniques, Endocrine; Evaluation Studies as Topic; Drug Development; Radioligand Assay; Drug Evaluation
• Other Study ID Numbers: D9690C00007; 2024-512992-11-00 (Registry Identifier: CTIS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No