A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Response of Guselkumab in Adult Participants With Celiac Disease
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 4
- 主要终点
- Number of Participants with Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of guselkumab compared to placebo in participants with celiac disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a body mass index (BMI) 16 to 45 kilogram per meter square (kg/m^2). Underweight participants (BMI 16 to 18 kg/m^2) may only be included if in the opinion of the investigator a participant was underweight due to active celiac disease and thus, may benefit from therapy but yet not be at significantly increased risk due to severe malabsorption or other conditions
- •Physician-diagnosed celiac disease with documented history of biopsy-proven celiac disease
- •Self-reported to be on a gluten-free diet (GFD) for at least 11 consecutive months prior to enrollment and have the willingness to continue to adhere to the same GFD while on study
- •Willing to take/ingest gluten-containing product at specific study timepoints only (if assigned to Module B)
- •Willing to undergo up to 3 on-study esophagogastroduodenoscopy (EGD) with biopsies
排除标准
- •Has a history of chronic inflammatory gastrointestinal disease (example, inflammatory bowel disease, extensive colitis, ulcerative jejunitis, eosinophilic esophagitis)
- •Has chronic infectious gastrointestinal illness, or acute infectious gastrointestinal illness within the 4-week period prior to screening
- •Currently has a malignancy or a history of malignancy within 5 years before screening (with the exception of a non-melanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study intervention administration or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study intervention); known history of lymphoproliferative disease, including monoclonal gammopathy of unknown significance, lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly
- •Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (example, recurrent pyelonephritis or chronic non-remitting cystitis), or open, draining, or infected skin wounds or ulcers
- •Has had previous treatment with guselkumab
研究组 & 干预措施
Module A (Without Gluten-Challenge): Guselkumab or Placebo
Participants in Module A (without gluten-challenge) will receive intravenous (IV) infusion of guselkumab or matching placebo as induction dose at every 4 weeks through Week 8 followed by subcutaneous (SC) injection of guselkumab or matching placebo at Week 12.
干预措施: Guselkumab (Drug)
Module A (Without Gluten-Challenge): Guselkumab or Placebo
Participants in Module A (without gluten-challenge) will receive intravenous (IV) infusion of guselkumab or matching placebo as induction dose at every 4 weeks through Week 8 followed by subcutaneous (SC) injection of guselkumab or matching placebo at Week 12.
干预措施: Placebo (Drug)
Module B (With Gluten-Challenge): Guselkumab or Placebo
Participants in Module B (with gluten-challenge) will receive IV infusion of guselkumab or matching placebo as induction dose at every 4 weeks through Week 8 followed by SC injection of guselkumab or matching placebo at Week 12.
干预措施: Guselkumab (Drug)
Module B (With Gluten-Challenge): Guselkumab or Placebo
Participants in Module B (with gluten-challenge) will receive IV infusion of guselkumab or matching placebo as induction dose at every 4 weeks through Week 8 followed by SC injection of guselkumab or matching placebo at Week 12.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to Week 28
An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are AEs with onset during the treatment phase or that are a consequence of a pre-existing condition that has worsened since baseline.
Number of Participants with Treatment-emergent Serious Adverse Events (SAEs)
时间窗: Up to Week 28
TEAEs are AEs with onset during the treatment phase or that are a consequence of a pre-existing condition that has worsened since baseline. A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.
Number of Participants with Clinically Significant Abnormalities in Vital Signs
时间窗: Up to Week 28
Number of participants with clinically significant vital signs abnormalities including temperature, pulse/heart rate, respiratory rate, and blood pressure (systolic and diastolic) (supine) will be reported.
Number of Participants with Clinically Significant Abnormalities in Laboratory Safety Tests
时间窗: Up to Week 28
Number of participants with clinically significant abnormalities in laboratory safety tests will be reported.
次要结局
- Change from Baseline in Marsh-Oberhuber Scores(Baseline and Week 16)
- Number of Participants with Antibodies to Guselkumab(Up to Week 28)
- Change from Baseline in Villus Height to Crypt Depth (Vh:Cd) Ratio(Baseline and Week 16)
- Change from Baseline in Number of Intraepithelial Lymphocytes (IELs).(Baseline and Week 16)
- Change from Baseline in Celiac Disease Symptom Diary (CDSD) Scores(Baseline and Week 16)
- Change from Baseline in Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) Score(Baseline and Week 16)
- Serum Concentrations of Guselkumab(Up to Week 28)
- Number of Participants with Neutralizing Antibodies to Guselkumab(Up to Week 28)
- Change from Baseline in Clinical Biomarkers High-Sensitivity C-Reactive Protein (hs-CRP)(Baseline, up to Week 28)
- Change from Baseline in Clinical Biomarker Fecal Calprotectin(Baseline, up to Week 28)