A Study of Guselkumab in Adult Participants With Celiac Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of guselkumab compared to placebo in participants with celiac disease.

Official Title
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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

Conditions
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Celiac Disease

Intervention / Treatment
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* Drug: Guselkumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Module A (Without Gluten-Challenge): Guselkumab or Placebo<br>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. | Drug: Guselkumab<br>* Guselkumab will be administered as IV infusion (induction dose) and SC injection.<br>Drug: Placebo<br>* Matching placebo to guselkumab will be administered as IV infusion (induction dose) and SC injection.<br>|
| Experimental: Module B (With Gluten-Challenge): Guselkumab or Placebo<br>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. | Drug: Guselkumab<br>* Guselkumab will be administered as IV infusion (induction dose) and SC injection.<br>Drug: Placebo<br>* Matching placebo to guselkumab will be administered as IV infusion (induction dose) and SC injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) | 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. | Up to Week 28 | 
| Number of Participants with Treatment-emergent Serious Adverse Events (SAEs) | 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. | Up to Week 28 | 
| Number of Participants with Clinically Significant Abnormalities in Vital Signs | 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. | Up to Week 28 | 
| Number of Participants with Clinically Significant Abnormalities in Laboratory Safety Tests | Number of participants with clinically significant abnormalities in laboratory safety tests will be reported. | Up to Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Villus Height to Crypt Depth (Vh:Cd) Ratio | Change from baseline in Vh:Cd ratio will be reported. | Baseline and Week 16 | 
| Change from Baseline in Number of Intraepithelial Lymphocytes (IELs). | Change from baseline in number of IELs will be reported. | Baseline and Week 16 | 
| Change from Baseline in Marsh-Oberhuber Scores | Change from baseline in marsh-oberhuber scores will be reported. Marsh-Oberhuber score is a classification system which grades histology specimens on 6 levels from normal to total villus atrophy to characterize tissue. | Baseline and Week 16 | 
| Change from Baseline in Celiac Disease Symptom Diary (CDSD) Scores | Change from baseline in CDSD scores will be reported. The CDSD is a daily electronic patient-reported outcome (ePRO) assessing the presence or absence of a broad range of celiac disease symptoms (diarrhea, spontaneous bowel movements, abdominal pain, bloating, nausea and tiredness). The CDSD includes 2 types of scores: a weekly symptom-specific severity score and a weekly total score. For each of the symptoms there is a possible score of 0 to 70. The total score for each week is then calculated by dividing each symptom-specific score by 10 and then summing them to get a possible total score of 0 to 70. | Baseline and Week 16 | 
| Change from Baseline in Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) Score | Change from baseline in CeD-GSRS will be reported. The CeD-GSRS is a modified version of the gastrointestinal symptom rating scale (GSRS). The GSRS is a questionnaire consisting of 15 symptom-specific items each graded on a 7-point Likert scale each with descriptive anchor. The scores are calculated by taking the mean of items within each of five scales: Abdominal Pain (AP), reflux, diarrhea, indigestion and constipation. The CeD-GSRS assesses 10 questions of the original GSRS. Higher scores represent more severe symptoms. | Baseline and Week 16 | 
| Serum Concentrations of Guselkumab | Serum concentrations of guselkumab over time, including steady-state concentrations will be reported. | Up to Week 28 | 
| Number of Participants with Antibodies to Guselkumab | Number of participants with antibodies to guselkumab will be reported. | Up to Week 28 | 
| Number of Participants with Neutralizing Antibodies to Guselkumab | Number of participants with neutralizing antibodies to guselkumab will be reported. | Up to Week 28 | 
| Change from Baseline in Clinical Biomarkers High-Sensitivity C-Reactive Protein (hs-CRP) | Change from baseline in clinical biomarker hs-CRP will be reported. | Baseline, up to Week 28 | 
| Change from Baseline in Clinical Biomarker Fecal Calprotectin | Change from baseline in clinical biomarker fecal calprotectin will be reported. | Baseline, up to Week 28 |