Celiac Disease MedDRA version: 16.1 Level: LLT Classification code 10007864 Term: Celiac disease System Organ Class: 100000004856
Conditions
Interventions
Product Name: ALV003
Pharmaceutical Form: Oral powder in sachet
INN or Proposed INN: Latiglutenase
CAS Number: 1360452-96-5
Current Sponsor code: ALV003
Concentration unit: mg milligram(s)
Concentrati
Sponsors
Alvine Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria: 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the effect of different dose levels of ALV003 administered for 12 weeks on mucosal morphometry as measured by the villus height to crypt depth ratio (Vh:Cd).;Secondary Objective: The secondary objectives are to: Determine the effect of different dose levels of ALV003 administered for 12 weeks on intraepithelial lymphocytes (IEL) Determine the effect of different dose levels of ALV003 administered for 12 weeks on celiac disease symptom frequency and severity as measured by the Celiac Disease Symptom Diary© (CDSD©) Assess the safety and tolerability of different dose levels of ALV003 administered for 12 weeks Exploratory objectives: Evaluate the effect of different dose levels of ALV003 on celiac-disease serologic titers Assess the effect of different dose levels of ALV003 on quality of life as measured by the Impact of Celiac Disease Symptoms Questionnaire (ICDSQ©) and the Short Form-12 (SF-12) v2® Health Survey Describe changes in primary and secondary endpoints following administration of study treatment for 24 weeks Additionally, serum levels of antibodies to ALV001 and ALV002 will be explored ;Primary end point(s): The primary endpoint is the change in intestinal mucosal morphometry (Vh:Cd) from baseline to Week 12;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are change from baseline to Week 12 in IELs, serology titers and patient-reported outcomes Additional analyses assessing the associations between the changes from baseline in mucosal morphometry (Vh:Cd) and the corresponding changes from baseline in serology endpoints and symptoms, as well as the associations between symptoms will be carried out;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Countries
Canada, Finland, Ireland, Norway, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
FinnMedi Oy
Outcome results
None listed