A study to learn if ZED1227 can improve continued celiac disease symptoms despite a gluten-free diet

Phase 2

Conditions: Coeliac disease
Digestive System

Registration Number: ISRCTN79155276

Lead Sponsor: Dr Falk Pharma (Germany)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 138

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 coeliac 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 coeliac 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 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
7. Biopsy showing VH:CrD ratio of = 2.5 from distal duodenum biopsies in Trial Period A
8. Negative diagnosis of Helicobacter pylori infection and no history of eradication within the last 2 months before biopsy sampling in Trial Period A
9. BMI between 17.0 and 35 kg/m², inclusively
10. Willingness to follow her/his usual dietary patterns, including eating at restaurants and others’ homes during the trial
11. Willingness 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. The investigator is responsible for determining whether the subject has adequate birth control for trial participation

Exclusion Criteria

1. Presence of hypo- or hyperthyroidism. A patient with a well-controlled thyroid disorder during the previous 3 months can be included.
2. Patients diagnosed with confirmed refractory coeliac disease type I (RCDI) or II (RCDII), with the exception that patients with a diagnosis of RCDI can be included if they don’t have clear signs of T cell monoclonality or atypical T cells (e.g., as revealed by CD3/CD8 immunohistochemistry) & if they don’t present with very severe symptoms &/or parameters of significant malabsorption & if they haven’t received prior treatment with immunosuppressants e.g. budesonide or azathioprine.
3. Severe complications of coeliac disease
4. Concomitant diseases of the intestinal tract, e.g. Crohn’s disease, ulcerative colitis, severe irritable bowel syndrome, microscopic colitis, small intestinal bacterial overgrowth, exocrine pancreatic insufficiency
5. History/presence of dermatitis herpetiformis.
6. History/presence of neurological disorders like ataxia or neuropathy
7. Any severe concomitant cardiovascular, renal, endocrine (type 1 diabetes mellitus with HbA1C >8% / 64 mmol/mol or hospitalisation or emergency visit for hyperglycaemia or hypoglycaemia within 12 months of screening), or psychiatric disorder or other disease.
8. Any prior invasive malignancy diagnosed within the last 5 years prior to Screening visit. Patients with basal cell carcinoma of the skin completely resected can be included.
9. Evidence of relevant systemic disease (e.g., active tuberculosis)
10. Abnormal hepatic function [alkaline aminotransferase (ALT) or alkaline phosphatase (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/intravenous) corticosteroids or immunomodulators (e.g., glucocorticoids, cyclosporine, methotrexate, anti-TNF-a therapy, anti-integrin therapy, Janus kinase inhibitors), high dose inhaled corticosteroids during the past 3 months before V0.
13. Continuous intake of drugs with suspicion of impact on villous atrophy, e.g.
14. Alcohol use > 12 g/d for women, >24 g/d for men within the past 12 months before screening.
15. Dual antiplatelet therapy or oral anticoagulants
16. Unwillingness to undergo gastrointestinal endoscopy with biopsy as required per protocol
17. Unwillingness to ingest SIGE bars
18. Allergies to SIGE bar nongluten ingredients (tapioca syrup, oats, almonds, rice crisp, chocolate, almond butter, cocoa butter, oat flour, glycerine, sunflower lecithin, salt, & natural flavours) or significant symptoms on eating the gluten-free SIGE bar
19. Known hypersensitivity reaction &/or allergy, including anaphylaxis, to wheat &/or gluten
20. 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
21. Known intolerance/hypersensitivity/resistance to the study drug & excipients or drugs of similar chemical structure/pharmacological profile.
22. Doubt about the subject’s cooperation, e.g., because of addiction to alcohol or drugs
23. Existing or intended pregnancy or breastfeeding
24. Affiliation with the investigator or persons working at the study sites or subject who is employed by the Sponsor
25. Subjects who are institutionalised because of legal/regulatory order
26. Participation in another trial of a therapeutic who received IMP within the last 30 days prior to V0