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: Active, not recruiting
• 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): 226
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Director
• Study Contact Backup: Name: Proactive Trial Transparency; Phone Number: (703) 345-1842; Email: proactiveceliac@proventionbio.com

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
  • Castilla Y Leon
    • Leon, Castilla Y Leon, Spain, 24071
      • Clinical Site
  • Catalunya
    • Terrassa, Catalunya, 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
Efficacy of PRV-015 in attenuating the symptoms of celiac disease in adult patients with NRCD as measured by the Celiac Disease Patient-Reported Outcome (CeD PRO) questionnaire	Celiac Disease Patient-Reported Outcome (CeD PRO)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of treatment with PRV-015 on other measures of disease activity	Intraepithelial lymphocyte (IEL) density	24 weeks
Incidence of treatment-emergent adverse events (TEAEs)	Safety endpoint	28 weeks
Serum trough concentrations of PRV-015 at scheduled visits	Characterize the pharmacokinetics (PK) of PRV-015	28 weeks
Incidence of anti-PRV-015 antibodies	Immunogenicity endpoint	28 weeks

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 (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 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 (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease
• Other Study ID Numbers: PRV-015-002b

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