A clinical trial to evaluate ZED1227 in comparison with placebo in subjects with celiac disease experiencing symptoms despite gluten-free diet

Phase 1

• Conditions: Treatment of celiac disease; MedDRA version: 20.0Level: LLTClassification code 10007864Term: Celiac diseaseSystem Organ Class: 100000004856; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2020-004612-97-NO
• Lead Sponsor: Dr. Falk Pharma GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-28
• Last Update Posted: 16 October 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1.Signed informed consent,
2.Men or women between 18 and 80 years of age, inclusively,
3.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,
4.Adherence to a gluten-free diet (GFD) for at least 12 months prior to V0,
5.Human leukocyte antigen DQ (HLA-DQ) typing compatible with celiac disease,
6.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, Visit 2, and Baseline Visit B as a gastrointestinal (GI) total mean symptom score (measured using CDSD) for the worst 25% of the days of = 2 on a 5-point scale,
7.Biopsy showing villous height to crypt depth (VH:CrD) ratio of ? 2.5 from distal duodenum biopsies at Visit 2 of Trial Period A,
8.Negative diagnosis of Helicobacter pylori infection and no eradication within the last two months before biopsy sampling in Trial Period A,
9.BMI between 17.0 and 35, inclusively,
10.Subject’s willingness to follow her/his usual dietary patterns, including eating at restaurants and others’ homes during the trial,
11.Willing to maintain current GFD throughout participation in the trial,
12.Negative pregnancy test in female subjects under 60 years of age at Screening Visit and Baseline Visit B,
13.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 (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 participation.

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 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

1. 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,
2.Subjects 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 IHC) 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,
3.Severe complications of celiac disease [e.g., enteropathy associated T-cell lymphoma (EATL), ulcerative jejunitis, perforation],
4.Concomitant diseases of the intestinal tract in addition to celiac disease, such as Crohn’s disease, ulcerative colitis, other forms of inflammatory bowel disease, severe irritable bowel syndrome, microscopic colitis, small intestinal bacterial overgrowth (SIBO), exocrine pancreatic insufficiency; any other active diseases of the intestinal tract (e.g., active, untreated peptic ulcer, esophagitis, gastroesophageal reflux disease) that might, in the investigator’s opinion, interfere with assessment of symptoms of abdominal pain, diarrhoea, or other components of celiac disease,
5.History or presence of dermatitis herpetiformis,
6.History or presence of neurological disorders like ataxia or neuropathy (mild neuropathy, related or unrelated to celiac disease, is not a reason for exclusion),
7.Any severe concomitant cardiovascular, renal, endocrine, or psychiatric disorder or other disease, which in the opinion of the investigator might have an influence on the subject’s compliance or the interpretation of the results,
8.History of cancer in the last five years,
9.Evidence of relevant systemic disease (e.g., active tuberculosis),
10.Abnormal hepatic function (ALT or ALP > 2.5 x ULN), liver cirrhosis, or portal hypertension,
11.Glomerular filtration rate = 60 ml/min/1.73 m²,
12.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,
13.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 [SSRIs1; 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
•mycophenolate2,3 (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) a

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified