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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Celiac Disease

Intervention / Treatment
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* Biological: PRV-015
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |