PRV-015 in Gluten-free Diet Non-responsive Celiac Disease (PROACTIVE)

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of PRV-015 in Adult Patients With Non-Responsive Celiac Disease as an Adjunct to a Gluten-free Diet

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).

Study Overview

• Status: Completed
• Conditions: Celiac Disease
• Intervention / Treatment: Other: Placebo; Biological: PRV-015

Detailed Description

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
• Enrollment (Actual): 388
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S4K1
      • Clinical Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Clinical Site
• Spain
  • Girona, Spain, 17007
    • Clinical Trial Site
  • Lleida, Spain, 25196
    • Clinical Trial Site
  • Madrid, Spain, 28034
    • Clinical Site
  • Madrid, Spain, 28041
    • Clinical Site
  • Madrid, Spain, 28222
    • Clinical Site
  • Andalusia
    • Seville, Andalusia, Spain, 41013
      • Clinical Site
  • Castille and León
    • León, Castille and León, Spain, 24071
      • Clinical Site
  • Catalonia
    • Terrassa, Catalonia, Spain, 082211
      • Clinical Trial Site
• United States
  • California
    • Los Angeles, California, United States, 90036
      • Clinical Site
    • Ventura, California, United States, 93003
      • Clinical Site
  • Colorado
    • Denver, Colorado, United States, 80209
      • Clinical Site
  • Florida
    • Leesburg, Florida, United States, 34748
      • Clinical Site
    • Tampa, Florida, United States, 33613
      • Clinical Site
    • Winter Park, Florida, United States, 32789
      • Clinical Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Clinical Site
    • Northbrook, Illinois, United States, 60062
      • Clinical Trial Site
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Clinical Site
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Clinical Site
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Clinical Site
  • New York
    • Brooklyn, New York, United States, 11235
      • Clinical Trial Site
    • New Windsor, New York, United States, 12553
      • Clinical Site
    • New York, New York, United States, 10032
      • Clinical Trial Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Clinical Site
  • Ohio
    • Dublin, Ohio, United States, 43016
      • Clinical Trial Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Clinical Site
    • Uniontown, Pennsylvania, United States, 14401
      • Clinical Site
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Clinical Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Clinical Trial Site
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Clinical Site
  • Texas
    • Cedar Park, Texas, United States, 78613
      • Clinical Trial Site
    • Garland, Texas, United States, 75044
      • Clinical Site
  • Utah
    • West Jordan, Utah, United States, 84088
      • Clinical Site
  • Washington
    • Bellevue, Washington, United States, 98004
      • Clinical Site
    • Tacoma, Washington, United States, 98405
      • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRV-015 Low Dose; PRV-015 Low Dose, sterile solution for subcutaneous administration	Biological: PRV-015; Fully human monoclonal antibody against interleukin 15 (IL-15)
Experimental: PRV-015 Medium Dose; PRV-015 Medium Dose, sterile solution for subcutaneous administration	Biological: PRV-015; Fully human monoclonal antibody against interleukin 15 (IL-15)
Experimental: PRV-015 High Dose; PRV-015 High Dose, sterile solution for subcutaneous administration	Biological: PRV-015; Fully human monoclonal antibody against interleukin 15 (IL-15)
Placebo Comparator: Placebo; Placebo, sterile solution for subcutaneous administration	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (average of Day -7 to Day -1) up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
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.	From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
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.	From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
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.	From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
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.	From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
Number of Participants With Anti-PRV-015 Antibodies	Blood samples were collected to determine the presence of anti-drug antibodies by immunoassay.	Baseline (Day 1) and Weeks 2, 4, 12, 22, 24 and 28
Minimum Serum Concentrations (Cmin) of PRV-015	Blood samples were collected at specified timepoints to determine the Cmin.	Pre-dose on Day 1 and Weeks 2, 4, 8, 12, 16, 20, 22, 24 and 28

Collaborators and Investigators

• Sponsor: Provention Bio, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

Helpful Links

• Proactive Celiac Study website for patient information.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2020
• Primary Completion (Actual): July 30, 2024
• Study Completion (Actual): July 30, 2024

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Malabsorption Syndromes; Nutritional and Metabolic Diseases; Celiac Disease
• Other Study ID Numbers: PRV-015-002b; DRI18114 (Other Identifier: Sanofi Identifier); 2020-000649-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No