Safety and Efficacy of ALV003 for the Treatment of Celiac Disease

Study Overview
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Brief Summary
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A phase 2a study to evaluate the safety and efficacy of ALV003 to treat celiac disease.

Detailed Description
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Double-blind, placebo controlled study of the efficacy, safety and tolerability of 6-weeks treatment of ALV003 in patients with well-controlled celiac disease. Approximately 110 biopsy proven celiac disease patients will be randomized to treatment with ALV003 or placebo in a 1:1 ratio. Patients will be required to have a pre-dose and a post-treatment intestinal biopsy, and also will be required to ingest a foodstuff that contains a specified amount of gluten during the active phase of the study along with the study treatment. Patients will return to the clinic weekly for the first two weeks, then every two weeks thereafter for safety visits. Patients will return to the clinic 28 days after completion of treatment for final safety and follow-up. Safety will be closely monitored throughout the study including laboratory parameters and clinical assessment of adverse events.

Official Title
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A Phase 2a, Double-Blind, Placebo Controlled Study of the Efficacy, Safety and Tolerability of 6-weeks Treatment With ALV003 In Patients With Well-Controlled Celiac Disease

Conditions
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Celiac Disease

Intervention / Treatment
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* Biological: ALV003
* Biological: ALV003 placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of biopsy-proven celiac disease Adherence to a gluten-free diet TG2 antibody negative Signed informed consent Exclusion Criteria: Active dermatitis herpetiformis History of IgE-mediated reactions to gluten Use of specific medications 6 months prior to entry History of alcohol abuse or illicit drug use Current untreated or GI disease Positive pregnancy test Received any experimental drug within 14 days of randomization Uncontrolled chronic disease or condition Uncontrolled complications of celiac disease Any medical condition, which could adversely affect participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: ALV003<br>ALV003 is an orally administered mixture of two recombinant proteases (cysteine endoprotease B-isoform 2 and prolyl endopeptidase) engineered to degrade gluten into non-immunogenic fragments, by targeting the glutamine and proline residues common in gluten. | Biological: ALV003<br>* ALV003 is an orally administered mixture of two enzymes (cysteine endoprotease B-isoform 2 and prolyl endopeptidase).<br>|
| Placebo Comparator: Placebo comparator<br>Excipients for ALV003 absent the experimental compounds | Biological: ALV003 placebo<br>* ALV003 is an orally administered mixture of two enzymes (cysteine endoprotease B-isoform 2 and prolyl endopeptidase).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Intestinal mucosal morphology |  | 6 weeks | 
| Safety: Tolerability of ALV003 |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Change in intestinal intraepithelial lymphocyte numbers/phenotype |  | 6 weeks | 
| Efficacy: Change in serological markers of celiac disease |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Celiac Disease, Coeliac Disease, Celiac Sprue, Keliakia