Bioequivalence Study of Nexvax2 in Subjects With Celiac Disease

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

Detailed Description
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A Phase 1, randomized,double-blind, placebo-controlled clinical study of Nexvax2, in adult subjects with confirmed CeD who, have been following a gluten free diet for at least 12 consecutive months prior to screening. The study will evaluate the safety and tolerability of Nexvax2 administered subcutaneously and will compare the bioavailability of subcutaneous versus intradermal administration. The study plan consists of 3 periods: a screening period of 3 to 5 weeks, a 46-day treatment period, and a 30-day post-treatment observational follow-up visit.

Official Title
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A Phase 1 Study of Nexvax2 Administered Subcutaneously After a Screening Gluten Food Challenge That Compares Relative Bioavailability With Intradermal Administration in Non-homozygous HLA-DQ2.5+ Adults With Celiac Disease

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

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 on one occasion during screening. Able to read and understand English. Exclusion Criteria: 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 (Arm A)<br> | Biological: Nexvax2<br>* Nexvax2 injections: 14 in total at twice weekly intervals<br>|
| Experimental: Nexvax2 (Arm B)<br> | Biological: Nexvax2<br>* Nexvax2 injections: 14 in total at twice weekly intervals<br>|
| Placebo Comparator: Nexvax2 Placebo (Arm C)<br> | Biological: Placebo<br>* Placebo injections: 14 in total at twice weekly intervals<br>|
| Placebo Comparator: Nexvax2 Placebo (Arm D)<br> | Biological: Placebo<br>* Placebo injections: 14 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 |
| --- | --- | --- |
| Safety of Nexvax 2 administered subcutaneously (SQ) | Treatment emergent adverse events (TEAEs) will be summarized by treatment group and treatment arm, severity (grades as defined in CTCAE, Version 4.03), relationship to IP, 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. | Treatment Period: 7 weeks | 
| Evaluate bioavailability of the constituents of Nexvax2 after SQ versus intradermal (ID) administration | Blood draws for plasma concentration | Treatment Period: 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the pharmacodynamics (PD) of the maintenance dose levels of Nexvax2 administered SQ and ID | Blood draw collected for cytokines | Treatment Period: 7 weeks | 
| Evaluate area under the plasma concentration-time curve for the constituents of Nexvax2 in SQ versus ID maintenance doses. | Blood draw collected for Pharmacokinetic (PK) sample | Treatment Period: 7 weeks | 
| Compare elimination half life properties for the constituents of Nexvax2 in SQ versus ID maintenance doses. | Blood draw collected for PK | Treatment Period: 7 weeks | 
| Compare time to maximal plasma concentration for the constituents of Nexvax2 in SQ versus ID maintenance doses. | Blood draw collected for PK | Treatment Period: 7 weeks |