PRV-015 in Gluten-free Diet Non-responsive Celiac Disease

Provention Bio, a Sanofi Company388 enrolled

Overview

This study will evaluate the efficacy and safety of PRV-015 in adult patients with non-responsive celiac disease (NRCD) who are on a gluten-free diet (GFD).

PRV-015-002b is a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of 3 dose regimens of PRV-015 in adult patients with NRCD who are on a GFD. Eligible subjects include male or female adults, 18 to 70 years of age, with a diagnosis of celiac disease and have followed a GFD for at least 12 consecutive months, yet continue to experience symptoms. Study drug (1 of the 3 doses of PRV-015 or placebo) will be administered in a double-blind fashion, followed by a safety follow-up period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

388

Conditions

Celiac Disease

Interventions

PRV-015BIOLOGICAL

Fully human monoclonal antibody against interleukin 15 (IL-15)

PlaceboOTHER

Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * A diagnosis of celiac disease by intestinal biopsy * Following a GFD for at least 12 consecutive months * Must have detectable (above the lower limit of detection) serum celiac-related antibodies * Must have human leukocyte antigen DQ (HLA-DQ) typing consistent with celiac disease (DQ2 and/or DQ8) * Subjects must have had at least one of the following symptoms at least once per week during the month before screening: diarrhea, loose stools, abdominal pain, abdominal cramping, bloating, or gas. * Body weight between 35 and 120 kg Exclusion Criteria: * Current diagnosis of any severe complication of celiac disease, such as refractory celiac disease type 1 (RCD-I) or RCD-II, enteropathy-associated T-cell lymphoma (EATL), ulcerative jejunitis, or gastrointestinal (GI) perforation * Diagnosis of any chronic, active GI disease other than celiac disease * Presence of any active infection * Selective immunoglobulin A (IgA) deficiency, defined as having undetectable levels of IgA * Known or suspected exposure to coronavirus disease 2019 (COVID-19) infection in the 4 weeks before screening * Administration of a live vaccine within 14 days prior to randomization and the first administration of study drug * History or presence of any clinically significant disease that, in the opinion of the Investigator, may confound the subject's participation and follow-up in the clinical trial or put the subject at unnecessary risk * Females who are pregnant or planning to become pregnant during the study period, or who are currently breastfeeding

Locations (38)

Outcomes

Primary Outcomes

Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Abdominal Symptoms Domain Score Through Week 24

The CeD PRO questionnaire was captured daily in the eDiary. The questionnaire included 9 items: abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache and tiredness. Participants were asked to rate their symptom severity on an 11-point scale and scores range from 0 (not experiencing the symptom) to 10 (the worst possible symptom experience). Abdominal Symptoms domain included abdominal cramping, abdominal pain, bloating and gas. Total score for abdominal symptoms domain range from 0 to 40. Higher scores indicated worse outcome. Baseline abdominal symptoms domain score was defined as the average of the daily scores for the last week of the placebo run-in period.

Time frame: Baseline (average of Day -7 to Day -1) up to Week 24

Secondary Outcomes

Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Diarrhea and Loose Stool Domain Score Through Week 24

The CeD PRO questionnaire was captured daily in the eDiary. The questionnaire included 9 items: abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache and tiredness. Participants were asked to rate their symptom severity on an 11-point scale and scores range from 0 (not experiencing the symptom) to 10 (the worst possible symptom experience). Diarrhea and loose stool domain included diarrhea and loose stool. Total score for diarrhea and loose stool domain range from 0 to 20. Higher scores indicated worse outcome. Baseline diarrhea and loose stool domain score was defined as the average of the daily scores for the last week of the placebo run-in period.

Time frame: Baseline (average of Day -7 to Day -1) up to Week 24

Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Total Gastrointestinal (GI) Score Through Week 24

The CeD PRO questionnaire was captured daily in the eDiary. The questionnaire included 9 items: abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache and tiredness. Participants were asked to rate their symptom severity on an 11-point scale and scores range from 0 (not experiencing the symptom) to 10 (the worst possible symptom experience). Total GI domain included abdominal symptoms domain, diarrhea, loose stool and nausea. Total GI score range from 0 to 70. Higher scores indicated worse outcome. Baseline GI score was defined as the average of the daily scores for the last week of the placebo run-in period.

Data from ClinicalTrials.gov

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Clinical Site

Los Angeles, California, United States

Clinical Site

Ventura, California, United States

Clinical Site

Denver, Colorado, United States

Clinical Site

Leesburg, Florida, United States

Clinical Site

Tampa, Florida, United States

Clinical Site

Winter Park, Florida, United States

Clinical Site

Chicago, Illinois, United States

Clinical Trial Site

Northbrook, Illinois, United States

Clinical Trial Site

Chevy Chase, Maryland, United States

Clinical Site

Boston, Massachusetts, United States

...and 28 more locations

Time frame: Baseline (average of Day -7 to Day -1) up to Week 24

Absolute Change From Baseline in Intraepithelial Lymphocyte (IEL) Density at Week 24

The small intestinal mucosal inflammation was measured by IEL density using immunohistochemistry. Baseline was defined as IEL density from the esophagogastroduodenoscopy biopsy conducted during the run-in period.

Time frame: Baseline to Week 24

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs)

An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. AESIs included severe opportunistic infections and hypersensitivity reactions of at least moderate severity. A TEAE was defined as an AE that occurred from the first dose of post-randomization study drug administration through the end of the study.