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)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 24
- 试验地点
- 18
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 to 80 years of age.
- •Diagnosis of Crohn's disease established with clinical AND at least one of imaging, endoscopic, and/or histopathologic evidence.
- •Ileostomy (including Kock pouch) 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 from 5 to 25 cm (20cm length) proximal to the stoma. Participants with inflammation in additional intestinal segments are not excluded.
- •Capable of giving signed informed consent.
排除标准
- •Concomitant additional gastrointestinal luminal inflammatory diseases including, but not limited to, infectious enteritis, ischaemic bowel, inflammation and strictures caused by previous radiation therapy
- •Strictures/stenoses preventing passage of endoscope throughout the specified segment (up to 25 cm of ileum)
- •Short bowel syndrome
- •Within 3 months prior to screening:
- •Diagnosis of peritonitis or need treatment of peritonitis
- •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 and/or fistulae which are adequately drained 4 weeks prior to randomization, and intra-abdominal 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:
- •Adenomatous colonic/rectal polyps that have not been removed
- •Intestinal dysplasia
- •Not undertaking appropriate surveillance, if indicated, for colorectal dysplasia/malignancy
- •Family history of early onset colorectal cancer, established diagnosis of HNPCC pancolitis for >8years duration without up-to-date colorectal cancer surveillance (can be performed during screening endoscopy if considered clinically appropriate by Investigator)
- •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:
- •An anti-TNF biologic within 8 weeks prior to randomization, unless therapeutic drug monitoring is performed, and drug concentrations are undetectable.
- •Any biologic targeting immune response other than an anti-TNF (including vedolizumab and ustekinumab) within 12 weeks prior to randomization unless validated therapeutic drug monitoring is performed, and drug concentrations are indetectable. Biologics not targeting immune response (eg, denosumab) will not be contraindicated.
- •Other advanced small molecule treatments for Crohn's disease (including JAK inhibitors or S1P modulators) within 4 weeks prior to randomization
- •Cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, or tacrolimus within 4 weeks prior to randomization
- •Treatment with apheresis (eg, Adacolumn, Cellsorba) within 4 weeks prior to randomization
- •Administration of any live vaccine within 4 weeks prior to randomization, or planned administration of any such vaccine during the study
- •Faecal microbiota transplantation within 4 weeks prior to randomization
- •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)
- •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
- •5-aminosalicylates within 2 weeks
- •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. Topical antimicrobials or antimicrobials for the treatment of uncomplicated urinary tract infection may be allowed at the Medical Monitor's discretion.
- •Evidence of chronic hepatitis B or C infection defined as:
- •HBV: HBsAg positive or HBcAb positive
- •HCV: Positive result for HCV Ab is exclusionary unless HCV RNA is undetectable, and at least 12 weeks post anti-viral treatment of HCV (if treated).
- •History of TB (active or latent) unless an appropriate course of treatment has been completed.
- •Positive diagnostic TB test at screening (defined as positive QuantiFERON test). In cases where the QuantiFERON test is indeterminate, the patient may have the test repeated once and if their second test is negative, they will be eligible. In the event a second test is also indeterminate, the Investigator has the option to undertake PPD testing. If the PPD reaction is <5mm, then the patient is eligible. If the reaction is ≥ 5 mm, or PPD testing is not undertaken, the patient is not eligible. If there has been a history of completed treatment for TB and, per specialist opinion, a positive QuantiFERON test reflects previous infection only and no current active or latent infection, the participant could be included.
- •History of serious opportunistic infection (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) 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, congenital and/or acquired aetiologies, including, but not limited to:
- •HIV infection (patients with positive results of HIV testing by the central laboratory will be excluded)
- •Splenectomy
- •Previous allogenic bone marrow transplant or history of organ or cell-based transplantation (eg, islet cell transplantation or autologous stem cell transplantation) with the exception of corneal transplant
- •Primary immune deficiency diseases, excluding selective IgA deficiency.
- •Abnormal laboratory results at screening:
- •Haemoglobin < 8 g/dL
- •Neutrophil count < 1,500/μL (or < 1.5 × 109/L); a re-test is allowed during screening in cases of mild neutropenia clinically suspected to be transient
- •Lymphocytes < 500/μL (or < 0.5 × 109/L)
- •Liver function tests: AST/ALT/ALP > 2 × ULN; or TBL ≥ 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%)
- •eGFR according to CKD-EPI formula < 30 mL/min
- •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
- 另有 21 项未显示
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Other)
AZD7798
AZD7798
干预措施: AZD7798 (Drug)
结局指标
主要结局
Number of participants with adverse events
时间窗: from Week 0 to Week 12
Summary of any adverse events and also by MedDRA SOC and Preferred term
Number of participants with abnormal values in haematology: complete blood count (CBC)
时间窗: from Week 0 to Week 12
The variables platelet count, red blood cell (RBC) count, haemoglobin, haematocrit will be summarized with descriptive statistics
Number of participants with abnormal values in haematology: white blood cell (WBC) count
时间窗: from Week 0 to Week 12
The variables neutrophils, lymphocytes, monocytes, eosinophils, and basophils will be summarized with descriptive statistics
Number of participants with abnormal values in haematology: RBC
时间窗: from Week 0 to Week 12
The variables mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and percentage of reticulocytes will be summarized with descriptive statistics
Number of participants with abnormal Vital signs: Blood pressure
时间窗: from Week 0 to Week 12
Systolic and diastolic blood pressure will be summarized by descriptive statistics
Number of participants with abnormal Vital signs: Pulse rate
时间窗: from Week 0 to Week 12
Pulse rate will be summarized by descriptive statistics
Number of participants with abnormal values in clinical chemistry: kidney function
时间窗: from Week 0 to Week 12
The variables creatinine and blood urea nitrogen (BUN) will be summarized with descriptive statistics
Number of participants with abnormal values in clinical chemistry: electrolytes
时间窗: from Week 0 to Week 12
The variables potassium, sodium, and calcium will be summarized with descriptive statistics
Number of participants with abnormal values in clinical chemistry: liver function
时间窗: from Week 0 to Week 12
The variables ALT (Alanine Aminotransferase), AST (Aspartate Aminotransferase), and ALP (alkaline phosphatase), and albumin will be summarized with descriptive statistics
Number of participants with abnormal values in clinical chemistry: hs-CRP
时间窗: from Week 0 to Week 12
The variable hs-C-reactive protein will be summarized with descriptive statistics
Number of participants with abnormal values in clinical chemistry: glucose
时间窗: from Week 0 to Week 12
The variable glucose will be summarized with descriptive statistics
Number of participants with abnormal values in ECG readings
时间窗: from Week 0 to Week 12
12-lead ECGs will be obtained using an ECG machine, that automatically measures RR/HR, PR, QRS, QT and Corrected QT (QTc) intervals, and summarized with descriptive statistics
次要结局
- Difference in mean change from baseline in endoscopic score between active and placebo(Week 12)
- Number of participants with endoscopic response(Week 12)
- Number of participants with endoscopic remission(Week 12)
- Serum AZD7798 concentration(up to 52 Weeks)
- Incidence of anti-drug antibody response(up to 52 Weeks)
- Titre of anti-drug antibody response(up to 52 Weeks)
- Number of participants with adverse events in active treatment(from Week 12 to Week 52)
- Number of participants with abnormal vital signs: Blood pressure(from Week 12 to Week 52)
- Number of participants with abnormal vital signs: Pulse rate(from Week 12 to Week 52)
- Number of participants with abnormal values in haematology: complete blood count (CBC)(from Week 12 to Week 52)
- Number of participants with abnormal values in haematology: white blood cell (WBC) count(from Week 12 to Week 52)
- Number of participants with abnormal values in haematology: RBC(from Week 12 to Week 52)
- Number of participants with abnormal values in clinical chemistry: kidney function(from week 12 to week 52)
- Number of participants with abnormal values in clinical chemistry: electrolytes(from Week 12 to Week 52)
- Number of participants with abnormal values in clinical chemistry: liver function(from Week 12 to Week 52)
- Number of participants with abnormal values in clinical chemistry: hs-CRP(from Week 12 to Week 52)
- Number of participants with abnormal values in clinical chemistry: glucose(from Week 12 to Week 52)
- Number of participants with abnormal values in ECG readings(from week 12 to week 52)