A Study of the Safety, Efficacy and Tolerability of Nexvax-2 in Patients With Celiac Disease (CeD)

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled clinical study in human leukocyte antigen (HLA)-DQ 2.5+ adults with celiac disease (CeD).

Detailed Description
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A phase 2, randomized, double-blind, placebo-controlled clinical study of Nexvax2, in adults subjects with confirmed CeD who have been following a gluten free diet for at least 12 consecutive months prior to screening. This study will evaluate efficacy of Nexvax2 administered subcutaneously. The study plan consists of 3 periods: a screening period of 6 weeks, an approximately 16 week treatment period, and a 4 week post-treatment observational follow-up.

Official Title
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A Phase 2 Randomized, Double-blind, Placebo-controlled Study in HLA-DQ2.5+ Adults With Celiac Disease to Assess the Effect of Nexvax2 on Symptoms After Masked Gluten Food Challenge

Conditions
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Celiac Disease, Celiac, Intestinal Disease, Malabsorption Syndromes, Gastrointestinal Disease, Digestive System Disease, Gluten Sensitivity, Autoimmune Diseases

Intervention / Treatment
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* Biological: Nexvax2
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18 to 70 years of age (inclusive) History of medically diagnosed celiac disease (CeD) that included duodenal biopsy Maintenance of gluten free diet (GFD) for at least 12 consecutive months prior to screening. Willingness to consume a moderate amount of gluten Able to read and understand English Worsening of GI symptoms in response to an oral gluten challenge HLA DQ 2.5 positive Exclusion Criteria: Unwilling or unable to perform self-injections History of inflammatory bowel disease and/or microscopic colitis. Any medical condition or lab abnormality that in the opinion of the investigator may interfere with study conduct or would impact the immune response (other than CeD), confound interpretation of study results, or pose an increased risk to the subject. Use of immunomodulatory or immune-suppressing medical treatment during the 6 months prior to screening Use of oral or parenteral immunomodulatory corticosteroids, within the 6 weeks prior to screening. Topical or inhaled corticosteroids are acceptable. Receipt of any investigational drug or participation in another clinical study within 6 months prior to screening. Females who are lactating or pregnant Receipt of any vaccine within 1 week prior to planned first day of the treatment period.

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: Nexvax2<br> | Biological: Nexvax2<br>* Nexvax2 subcutaenous (SQ) injections: 32 in total, at twice weekly intervals<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Placebo SQ injections: 32 in total, at twice weekly intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Nexvax2 compared to placebo in reducing Celiac Disease (CeD) associated GI symptoms. | Measured by the CeD Patient Reported Outcome (CeD PRO) between baseline and day of the first masked food challenge (MFC) containing gluten. The CeD PRO captures patient ratings for a number of CeD-associated symptoms, on a 0 to 10 scale, with 0 being absent or no symptoms, and 10 being the most severe symptoms. The Total GI domain score is calculated as an average of summed average and individual symptom scores relevant to the GI tract, to yield a value of 0 to 10. | 79 to 93 days after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate efficacy of Nexvax 2 compared with placebo on immune-system activation after the first MFC containing gluten. | Differences in levels of pharmacodynamic markers between baseline and day of the first MFC containing gluten. | 79 to 93 days after baseline | 
| Evaluate efficacy of Nexvax2 compared with placebo in reducing CeD associated GI symptom sub-domains. | Differences in daily GI symptom domain score between baseline and day of the first MFC containing gluten. | 79 to 93 days after baseline | 
| Evaluate efficacy of Nexvax2 compared with placebo in reducing individual GI symptoms. | Differences in each of the individual GI item scores in the CeD PRO between baseline and day of the first MFC containing gluten. GI symptoms assessed on the CeD PRO include abdominal cramping, abdominal pain, bloating, diarrhea, gas, loose stool, and nausea. Each are rated on a 0 to 10 scale, where 0 is absent and 10 is the most severe. | 79 to 93 days after baseline | 
| Incidence of Treatment-Emergent Adverse Events (TEAEs) in assessing safety and tolerability of Nexvax2. | Treatment emergent adverse events (TEAEs) will be summarized by treatment arm, severity, relationship to study drug and to known or potential gluten exposure, and phase of treatment and presented as the number and percentage of patients reporting an event(s) as well as the number of events reported. | Study Duration: 21 weeks |