A Study to Evaluate the Efficacy and Safety of AMG 714 in Adult Patients With Celiac Disease

Study Overview
=================
Brief Summary
-----------------
This study is designed to evaluate the efficacy and safety of AMG 714 for the attenuation of the effects of gluten exposure in adult patients with celiac disease during a gluten challenge.

Official Title
-----------------
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of AMG 714 in Adult Patients With Celiac Disease

Conditions
-----------------
Celiac Disease

Intervention / Treatment
-----------------
* Biological: AMG 714
* Biological: Placebo
* Other: Placebo Gluten Challenge
* Other: Gluten Challenge


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of celiac disease by intestinal biopsy at least 12 months prior to screening On a gluten-free diet for at least 12 months Negative celiac serology Avoidance of pregnancy Exclusion Criteria: Severe complications of celiac disease, such as refractory celiac disease Celiac symptoms Other concomitant autoimmune disease Chronic, active gastrointestinal disease Infections, concomitant diseases Prohibited medications

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 714 150 mg<br>Participants received 150 mg AMG 714 via subcutaneous injection once every 2 weeks for a total of 6 doses over 10 weeks from day 0. Participants received gluten-free cookies twice a day for the first 2 weeks and gluten-containing cookies twice a day from weeks 2 to 12 (gluten-challenge). | Biological: AMG 714<br>* AMG 714 administered by subcutaneous injection<br>* Other names: PRV-015;Other: Placebo Gluten Challenge<br>* Gluten-free cookies (Finnish rusks)<br>Other: Gluten Challenge<br>* Gluten-containing cookies (Finnish rusks), 1-2 g gluten per serving<br>|
| Experimental: AMG 714 300 mg<br>Participants received 300 mg AMG 714 via subcutaneous injection once every 2 weeks for a total of 6 doses over 10 weeks from day 0. Participants received gluten-free cookies twice a day for the first 2 weeks and gluten-containing cookies twice a day from weeks 2 to 12 (gluten-challenge). | Biological: AMG 714<br>* AMG 714 administered by subcutaneous injection<br>* Other names: PRV-015;Other: Placebo Gluten Challenge<br>* Gluten-free cookies (Finnish rusks)<br>Other: Gluten Challenge<br>* Gluten-containing cookies (Finnish rusks), 1-2 g gluten per serving<br>|
| Placebo Comparator: Placebo<br>Participants received placebo subcutaneous injection once every 2 weeks for a total of 6 doses over 10 weeks from day 0. Participants received gluten-free cookies twice a day for the first 2 weeks and gluten-containing cookies twice a day from weeks 2 to 12 (gluten-challenge). | Biological: Placebo<br>* Matching placebo to AMG 714 administered by subcutaneous injection<br>Other: Placebo Gluten Challenge<br>* Gluten-free cookies (Finnish rusks)<br>Other: Gluten Challenge<br>* Gluten-containing cookies (Finnish rusks), 1-2 g gluten per serving<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Villous Height to Crypt Depth Ratio (VH:CD) at Week 12 | Attenuation of the effects of gluten exposure was assessed by measuring the percent change from baseline in villous height to crypt depth ratio after 10 weeks of gluten challenge. Villi are the small fingerlike projections that line the small intestine and promote nutrient absorption and are often shortened in patients with celiac disease. Crypts are grooves between the villi that are often elongated in patients with celiac disease. A decreased VH:CD ratio indicates worsening disease. Small bowel biopsies were performed at baseline and week 12; histological assessments were performed by a blinded central pathologist. | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Intraepithelial Lymphocyte Density at Week 12 | Intraepithelial lymphocytes (IELS) are white blood cells interspersed between epithelial cells of the small and large intestine where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen or immune-induced pathology. Increased intraepithelial lymphocytes is associated with celiac disease. Small bowel biopsies were performed at baseline and week 12; histological assessments were performed by a blinded central pathologist. | Baseline and week 12 | 
| Number of Participants With Improvement in Marsh Score at Week 12 | The Marsh classification system describes the stages of damage in the small intestine as seen under a microscope, with possible values of 0, 1, 2, 3a, 3b, or 3c. A score of 0 (best score) indicates that the intestinal lining is normal and celiac disease highly unlikely, a score of 3c (worst score) indicates increased intraepithelial lymphocytes, increased crypt hyperplasia and complete villi atrophy. Improvement is defined as a lower grade on the Marsh score scale compared to baseline. | Baseline and week 12 | 
| Percent Change From Baseline in Anti-Tissue Transglutaminase (tTG) Immunoglobulin A (IgA) Antibodies at Week 12 | Levels of anti-tTG IgA antibodies in serum were determined using an enzyme-linked immunosorbent assay (ELISA) immunoassay. | Baseline and week 12 | 
| Change From Baseline in Anti-Deamidated Gliadin Peptide (DGP) Antibodies at Week 12 | Levels of serum anti-DGP antibodies (immunoglobulin A [IgA] and immunoglobulin G [IgG]) were determined using ELISA immunoassay. | Baseline and week 12 | 
| Number of Weekly Bowel Movements at Baseline and Week 12 | Participants were asked to record every bowel movement during the study using an electronic diary. If no bowel movements were experienced on any given day, the participant was required to document this using the electronic diary. | Baseline and week 12 | 
| Number of Participants With Diarrhoea at Baseline and Week 12 | The Bristol Stool Form Scale (BSFS) is a pictorial aid to help study participants identify the shape and consistency of their bowel movements. Participants were asked to complete this form daily using an electronic diary at the time of each bowel movement. The BSFS categorizes bowel movements into 7 types, from Type 1 (separate hard lumps, like nuts; hard to pass) to Type 7 (watery, no solid pieces, entirely liquid). Diarrhoea was defined as at least one BSFS score >= 6 for the given week. | Baseline and week 12 | 
| Percent Change From Baseline in Total Weekly Gastrointestinal Symptom Rating Scale (GSRS) Score at Week 12 | The GSRS is a 15-question 7-scale questionnaire used to assess 5 dimensions of gastrointestinal syndromes: diarrhea, indigestion, constipation, abdominal pain, and reflux. Questions are scored between 1 (no discomfort at all) and 7 (very severe discomfort). The total GSRS score is calculated as the sum of the scores of all 15 questions, and ranges from 15 (no discomfort at all) to 105 (very severe discomfort in all 5 dimensions of gastrointestinal syndromes). | Baseline and 12 weeks | 
| Change From Baseline in Total Celiac Disease GSRS (CeD-GSRS) Score at Week 12 | The CeD-GSRS score is derived from a subset of questions from the GSRS questionnaire, including the diarrhea, indigestion, and abdominal pain domains (a total of 10 questions), which are each assessed on a scale of 1 (no discomfort at all) to 7 (very severe discomfort). The total CeD-GSRS score is calculated as the sum of the scores of all 10 questions, and ranges from 10 (no discomfort at all) to 70 (very severe discomfort in all celiac syndromes). | Baseline and 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
celiac, gluten, Interleukin 15 (IL-15), AMG 714, gluten challenge