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

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.

Primary Outcome Measures

1. 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.

Secondary Outcome Measures

1. 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.
2. 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.
3. 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.
4. 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.
5. Number of Participants With Potentially Clinically Important Changes in Hematology
   Blood samples were collected to determine the hematology laboratory important changes. CHG= Change from baseline hemoglobin.
6. Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry
   Blood samples were collected to determine the clinical chemistry laboratory important changes. ULN= Upper limit of normal, mmol/L= millimoles per liter and mcmol/L= micromoles per liter.
7. Number of Participants With Potentially Clinically Important Changes in Urinalysis
   Urine samples were collected to determine the important changes in urine. TNTC= Too numerous to count, LPF= Low power field and HPF= High power field.
8. Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight
   Participant's vital signs and body weight were examined to determine the important changes. Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate. mmHg= millimeters of mercury, DFB= Decrease from baseline and IFB= Increase from baseline.
9. Number of Participants With Anti-PRV-015 Antibodies
   Blood samples were collected to determine the presence of anti-drug antibodies by immunoassay.
10. Minimum Serum Concentrations (Cmin) of PRV-015
    Blood samples were collected at specified timepoints to determine the Cmin.