E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007864 |
E.1.2 | Term | Celiac disease |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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 < 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
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in intestinal mucosal morphometry (Vh:Cd) from baseline to Week 12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Ireland |
Norway |
Finland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |