A Study of Guselkumab in Adult Participants With Celiac Disease
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of guselkumab compared to placebo in participants with celiac disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Guselkumab
Guselkumab will be administered as IV infusion (induction dose) and SC injection.
Drug: Placebo
Matching placebo to guselkumab will be administered as IV infusion (induction dose) and SC injection.
|
| Experimental: 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. |
Drug: Guselkumab
Guselkumab will be administered as IV infusion (induction dose) and SC injection.
Drug: Placebo
Matching placebo to guselkumab will be administered as IV infusion (induction dose) and SC injection.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants with Treatment-emergent Adverse Events (TEAEs) [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) [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 [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 [Up to Week 28]
Number of participants with clinically significant abnormalities in laboratory safety tests will be reported.
Secondary Outcome Measures
- Change from Baseline in Villus Height to Crypt Depth (Vh:Cd) Ratio [Baseline and Week 16]
Change from baseline in Vh:Cd ratio will be reported.
- Change from Baseline in Number of Intraepithelial Lymphocytes (IELs). [Baseline and Week 16]
Change from baseline in number of IELs will be reported.
- Change from Baseline in Marsh-Oberhuber Scores [Baseline and Week 16]
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.
- Change from Baseline in Celiac Disease Symptom Diary (CDSD) Scores [Baseline and Week 16]
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.
- Change from Baseline in Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) Score [Baseline and Week 16]
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.
- Serum Concentrations of Guselkumab [Up to Week 28]
Serum concentrations of guselkumab over time, including steady-state concentrations will be reported.
- Number of Participants with Antibodies to Guselkumab [Up to Week 28]
Number of participants with antibodies to guselkumab will be reported.
- Number of Participants with Neutralizing Antibodies to Guselkumab [Up to Week 28]
Number of participants with neutralizing antibodies to guselkumab will be reported.
- Change from Baseline in Clinical Biomarkers High-Sensitivity C-Reactive Protein (hs-CRP) [Baseline, up to Week 28]
Change from baseline in clinical biomarker hs-CRP will be reported.
- Change from Baseline in Clinical Biomarker Fecal Calprotectin [Baseline, up to Week 28]
Change from baseline in clinical biomarker fecal calprotectin will be reported.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Have a body mass index (BMI) 16 to 45 kilogram per meter square (kg/m2). Underweight participants (BMI 16 to 18 kg/m2) 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
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Physician-diagnosed celiac disease with documented history of biopsy-proven celiac disease
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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
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Willing to take/ingest gluten-containing product at specific study timepoints only (if assigned to Module B)
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Willing to undergo up to 3 on-study esophagogastroduodenoscopy (EGD) with biopsies
Exclusion Criteria:
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Has a history of chronic inflammatory gastrointestinal disease (example, inflammatory bowel disease, extensive colitis, ulcerative jejunitis, eosinophilic esophagitis)
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Has chronic infectious gastrointestinal illness, or acute infectious gastrointestinal illness within the 4-week period prior to screening
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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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Trials Network | Lancaster | California | United States | 93534 |
| 2 | Clinical Research Institute of Michigan, LLC | Chesterfield | Michigan | United States | 48047 |
| 3 | West Michigan Clinical Research Center | Wyoming | Michigan | United States | 49519 |
| 4 | Hightower Clinical | Oklahoma City | Oklahoma | United States | 73102 |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR108914
- 2020-003539-40
- 64304500CLD1001