A Phase 2b, Randomized, Double-Blind, PLacebo-Controlled Dose-Ranging Study of the Efficacy and Safety of ALV003 Treatment in Symptomatic Celiac Disease Patients Maintained on a Gluten-Free Diet

Phase 1

Conditions: Celiac Disease
MedDRA version: 17.0Level: LLTClassification code 10007864Term: Celiac diseaseSystem Organ Class: 100000004856
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2013-003660-31-NO

Lead Sponsor: Alvine Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 500

Inclusion Criteria

Potential study participants must meet the following entry criteria:

Age 18 to 80 years

Physician-diagnosed celiac disease patients with documented history of biopsy-proven celiac disease; patients previously diagnosed only by positive serology and clinical response to exclusion of dietary gluten will require biopsy confirmation of celiac disease prior to randomization at Visit 4

Self-reported to be on a gluten-free diet (GFD) for at least 11 months prior to enrollment at Visit 2; patients attempting adherence to a GFD who previously participated in Alvine Study ALV003-1121 may be eligible if they otherwise meet entry criteria

Experienced at least one self-reported moderate or severe symptom included in the CDSD©, probably/likely as a result of gluten exposure, during the 28-day period prior to screening

Have daily telephone access in order to complete the CDSD©

Agree to maintain dosing of approved prescribed and OTC medications throughout the course of the study

Willing to take study treatment three times each day with each gluten-free major meal, with minimal ingestion outside of these meals

Willing to undergo two (2) on-study upper gastrointestinal endoscopies with duodenal biopsies

Willing and able to comply with all study procedures

Sign informed consent

Must read and understand native language of their country

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Potential study participants must NOT meet any of the following criteria:

History of known Immunoglobulin E (IgE)-mediated reaction to wheat (i.e., wheat allergy”)

Currently untreated or active: peptic ulcer disease, esophagitis (Los Angeles Classification = Grade C), irritable bowel syndrome, inflammatory bowel disease, or microscopic colitis

Active dermatitis herpetiformis

Patients with known rapid gastric emptying (e.g., post-bariatric surgery, Billroth I or II surgery)

Chronic infectious gastrointestinal illness, or acute infectious gastrointestinal illness within the 4 week period prior to enrollment

Known Refractory Celiac Disease (RCD1 or RCD2). RCD is characterized by persistent symptoms, severe malabsorption, and intestinal damage despite strict adherence to a GFD (in patients with RCD 1, the intraepithelial lymphocyte phenotype is normal; in RCD 2, there is a clonal aberrant phenotype of the intraepithelial lymphocyte)

Screening laboratory values
a.Elevated liver function tests (Alanine Aminotransferase [ALT], Aspartate Transaminase [AST], Alkaline Phosphatase [Alk Phos], or Gamma-Glutamyl Transferase [GGT]) > 2.5x ULN
b.Total bilirubin > 2x ULN
c.Serum creatinine > 1.5x ULN
d.Calcium < 8.0 mg/dL
e.Serum potassium < 3.0 mEq/L, > 5.5 mEq/L
f.Hemoglobin < 8.5 g/dL
g.Platelet count < 75.0 x 10^9/L or 75,000/mm3
h.Total white blood cell count (WBC) < 2.5 x 10^9/L or 2500/mm3
i.Total lymphocyte < 0.8 x 10^9/L or 800/mm3

For women of childbearing potential, positive pregnancy test at screening, or planning to become pregnant during the course of the study, or unwilling to practice effective birth control during the study

Expected use of anticoagulants or antiplatelet agents (e.g., warfarin, heparin, or clopidogrel or similar class), other than mini-dose (e.g., 81 mg aspirin), during the week prior to intestinal biopsies that, in the opinion of the endoscopist, would affect the safety of obtaining the biopsies

Change of dose or frequency of systemic glucocorticosteroid medications, oral budesonide, or mesalamine within 28-days prior to enrollment at Visit 2 and/or expected to change during the study

Use of angiotensin II receptor blockers (ARBs) within 28 days prior to enrollment at Visit 2 and during the study

History of alcohol abuse or habitual use of illicit drugs (e.g., amphetamines, barbiturates, benzodiazepines, cocaine, and opiates, including abuse of prescription opiates) within the past 6 months

Received any experimental drug within 30 days of enrollment at Visit 2; in the case of experimental protein therapeutics or vaccines, at least 6 months prior to enrollment

Other than oral contraceptives, use of prescribed medications or over-the-counter medications that in the opinion of the investigator might interfere with the study

Any medical condition, which, in the opinion of the study investigator, could adversely affect the patient’s participation in the trial, including the ability to tolerate two (2) upper gastrointestinal endoscopies with duodenal biopsies, or affect the trial integrity

Known allergy or hypersensitivity to any of the components of ALV003 (including sulfites), E. coli, or E. coli-derived proteins

Any study staff directly involved with the conduct of the study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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