A study to discover if ZED1227 can improve continued celiac disease symptoms despite a gluten-free diet
- Conditions
- Celiac DiseaseMedDRA version: 20.0Level: LLTClassification code: 10007864Term: Celiac disease Class: 10017947Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- CTIS2023-506150-21-00
- Lead Sponsor
- Dr. Falk Pharma GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 280
Signed informed consent, Willingness to follow her/his usual dietary patterns, including eating at restaurants and others’ homes during the trial, Willingness to maintain current GFD throughout participation in the trial, Negative pregnancy test in female subjects under 60 years of age at Screening Visit and Baseline Visit B, Women of child-bearing potential should use a highly effective method of birth control which is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptive pills, combined contraceptive patches and vaginal rings, copper containing intrauterine devices, sexual abstinence or vasectomised partner (see Table 11 for further information on acceptable and unacceptable birth control methods). The investigator is responsible for determining whether the subject has adequate birth control for trial participants, Men or women between 18 and 80 years of age, inclusively, Documented initial biopsy-proven diagnosis of celiac disease or, in case of missing histological documentation TG2-IgA > 10 x upper limit of normal (ULN) at diagnosis at least 12 months prior to V0, Adherence to a gluten-free diet (GFD) for at least 12 months prior to V0, Human leukocyte antigen DQ (HLA-DQ) typing compatible with celiac disease, At least one moderate or severe gastrointestinal symptom (i.e., diarrhoea, abdominal pain, bloating, or nausea) during the last 4 weeks prior to Baseline Visit A and last 3 weeks prior to Baseline Visit B as a GI total mean symptom score (measured using CDSD) for the worst 25% of the days of = 2 on a 5-point scale, Biopsy showing VH:CrD ratio of = 2.5 from distal duodenum biopsies in Trial Period A, Negative diagnosis of Helicobacter pylori infection and no history of eradication within the last two months before biopsy sampling in Trial Period A, BMI between 17.0 and 35 kg/m², inclusively
Presence of hypo- or hyperthyroidism. A patient with a thyroid stimulating hormone (TSH) level up to 25% higher than ULN or up to 25% lower than the lower limit of normal (LLN) but with normal free triiodothyronine (FT3) and free thyroxine (FT4) levels can be included in the trial. In addition, a patient with a well-controlled thyroid disorder during the previous 3 months can be included, Abnormal hepatic function [alkaline aminotransferase (ALT) or alkaline phosphatase (ALP) > 2.5 x ULN), liver cirrhosis, or portal hypertension, Glomerular filtration rate = 60 ml/min/1.73 m², Continuous intake of systemic (oral or intravenous) corticosteroids or immunomodulators (e.g., glucocorticoids, cyclosporine, methotrexate, anti-TNF-? therapy, anti-integrin therapy, Janus kinase inhibitors), high dose inhaled corticosteroids (> 1000 µg/d of beclomethasone dipropionate or equivalent) during the past 3 months before V0, Continuous intake of drugs with suspicion of impact on villous atrophy, such as •proton-pump inhibitors (PPIs; permitted at a regular dose equivalent to 20-40 mg/day pantoprazol, esomeprazole or equivalent), •selective serotonin reuptake inhibitors [SSRIs; low to medium dose (10-150 mg Fluvoxamine or equivalent dose of other SSRIs) permitted in case of long-term therapy (at least for 6 months)], •losartan (angiotensin II receptor blockers equivalent to 50 mg losartan permitted except for olmesartan forbidden at any dose) and •mycophenolate1,2 (forbidden at any dose) during the past 2 months before biopsy sampling in Trial Period A; •non-steroidal anti-inflammatory drugs (NSAIDs; maximal daily dose permitted 900 mg for ibuprofen, 500 mg for naproxen and 75 mg for diclofenac, except for one week before biopsy) and •acetylsalicylic acid (max daily dose permitted 100 mg) during the past 4 weeks before biopsy sampling at Baseline Visit A, Alcohol use > 12 g/d for women, > 24 g/d for men within the past 12 months before screening, Dual antiplatelet therapy [i.e., acetylsalicylic acid in combination with thienopyridines (clopidogrel, prasugrel, ticlopidine or ticagrelor)] or oral anticoagulants (i.e., warfarin, dabigatran, etexilate, rivaroxaban, apixaban), Unwillingness to undergo upper gastrointestinal endoscopy with biopsy at Baseline Visit A and Final/Withdrawal Visit, Unwillingness to ingest SIGE bars through run-in and treatment period, Food allergies to nongluten ingredients (tapioca syrup, oats, almonds, rice crisp, chocolate, almond butter, cocoa butter, oat flour, glycerine, sunflower lecithin, salt, and natural flavours) of the SIGE bar or significant symptoms upon ingestion of the gluten-free SIGE bar, Known hypersensitivity reaction and/or allergy, including anaphylaxis, to wheat and/or gluten, Patients diagnosed to have confirmed refractory celiac disease type I (RCDI) or II (RCDII), with the exception that patients with a diagnosis of RCDI can be considered for inclusion if they do not have clear signs of T cell monoclonality or atypical T cells (e.g., as revealed by CD3/CD8 immunohistochemistry) and if they do not present with very severe symptoms and/or parameters of significant malabsorption and if they have not received prior treatment with immunosuppressants such as budesonide or azathioprine, If more than 10% of planned enrolled subjects report a greater than 1 point improvement in PGI-S during Trial Period A, further subjects with > 1 point improvement in PGI-S will be excluded, Known intolerance/hypersensitivi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess one or more doses of ZED1227 capsules vs placebo for efficacy in: Improvement of celiac disease symptoms as assessed by Celiac Disease Symptom Diary (CDSD) in celiac disease subjects experiencing symptoms and having mucosal damage on a gluten-free diet.;Secondary Objective: To assess the efficacy of ZED1227 capsules for: •Changes in duodenal mucosal morphology as measured by morphometry (villous height to crypt depth, VH:CrD), •Changes in the severity of non-stool gastrointestinal (GI) symptoms (abdominal pain, bloating, nausea) as assessed by CDSD. To assess the safety and tolerability of ZED1227 in terms of adverse events (AEs) and laboratory parameters;Primary end point(s): Change in CDSD GI Specific Symptom Score (diarrhoea, abdominal pain, bloating, nausea) from Baseline Visit B (V2, Wk 3) to V5 (Wk 15).
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Change in VH: CrD from Baseline Visit A (V1, Wk 0) to V5 (Wk 15),;Secondary end point(s):Change in CDSD Non-Stool GI Symptom Score (abdominal pain, bloating, nausea) from Baseline Visit B (V2, Wk 3) to V5 (Wk 15),;Secondary end point(s):Change in duodenal mucosal inflammation measured as the density of CD3-positive intraepithelial lymphocytes (IELs) from Baseline Visit A (V1, Wk 0) to V5 (Wk 15).