ZED1227 Capsules in Patients Suffering from Symptoms Despite a Gluten-Free Diet
Summary description of the study
The aim of this study is to investigate the efficacy of three different dosages (30 mg per day, 50 mg per day, and 75 mg per day) as well as two different dosing regimens. The investigational product ZED1227 is a capsule for oral administration, which aims to inhibit the activation of inflammatory processes and the destruction of the intestinal mucosa due to gluten consumption, thereby preventing corresponding complaints. The total participation lasts up to 27 weeks. The study consists of 3 sections: The preliminary examinations are conducted within 6 weeks. This is followed by a 17-week treatment phase. Participation ends after an additional 4-week treatment-free follow-up phase. A total of 9 visits are planned. After 2 weeks of treatment and at the end of the observation phase, a small bowel endoscopy should be performed, during which small mucosal samples (biopsies) will be taken. Participants are to maintain their usual dietary habits, including eating out at restaurants and at others' homes, and must take one ZED1227 capsule unchewed 30 minutes before each major meal (i.e., breakfast, lunch, dinner). The study is conducted with four different treatment groups. 75% of participants receive different dosages of the ZED1227 capsules (either 30 mg, 50 mg, or 75 mg) and 25% receive placebo (placebo is a "sham treatment" that looks like the investigational product but contains no active ingredient). Regardless of which group one is assigned to, all participants will use the placebo for several weeks.
(BASEC)
Intervention under investigation
Efficacy of ZED1227 Capsules for the Supportive Treatment of Celiac Disease.
(BASEC)
Disease under investigation
Celiac Disease
(BASEC)
- A celiac disease diagnosis confirmed by documented initial biopsy or, in the absence of histological documentation, TG2-IgA > 10 x upper limit of normal (ULN) at the time of diagnosis at least 12 months prior to screening - Adherence to a gluten-free diet (GFD) for at least 12 months prior to participation - Presence of celiac disease-associated features of human leukocyte antigen DQ (HLA-DQ) (BASEC)
Exclusion criteria
- Presence of hypo- or hyperthyroidism. A patient with well-controlled thyroid disease in the last 3 months may be included in the study - Patients with a confirmed diagnosis of refractory celiac disease type I (RCDI) or II (RCDII), except that patients with a diagnosis of RCDI may be considered for inclusion if they do not have clear signs of T-cell monoclonality or atypical T-cells and if there are no very severe symptoms and/or parameters of significant malabsorption present and no prior treatment with immunosuppressants such as budesonide or azathioprine has occurred - Comorbidities that, in the opinion of the investigator, may affect the assessment of symptoms of abdominal pain, diarrhea, or other components of celiac disease (BASEC)
Trial sites
Bern, St. Gallen, Zurich
(BASEC)
Sponsor
Dr. Falk Pharma GmbH, Freiburg, Germany Dr. Falk Pharma AG, Glattbrugg, Switzerland
(BASEC)
Contact
Contact Person Switzerland
Ralf Mohrbacher
+49 761 1514 156
mohrbacher@clutterdrfalkpharma.deDr. Falk Pharma GmbH
(BASEC)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
17.09.2021
(BASEC)
ICTRP Trial ID
EUCTR2020-004612-97 (ICTRP)
Official title (approved by ethics committee)
A phase IIb, double-blind, randomised, placebo-controlled, trial to evaluate the efficacy and tolerability of ZED1227 in celiac disease subjects experiencing symptoms despite gluten-free diet (BASEC)
Academic title
A phase IIb, double-blind, randomised, placebo-controlled trial to evaluate the efficacy and tolerability of ZED1227 in celiac disease subjects experiencing symptoms despite gluten-free diet - ZED1227 for treatment of symptomatic celiac disease subjects (ICTRP)
Public title
A clinical trial to evaluate ZED1227 in comparison with placebo in subjects with celiac disease experiencing symptoms despite gluten-free diet (ICTRP)
Disease under investigation
Treatment of celiac disease
MedDRA version: 20.0Level: LLTClassification code 10007864Term: Celiac diseaseSystem Organ Class: 100000004856;Therapeutic area: Diseases [C] - Digestive System Diseases [C06] (ICTRP)
Intervention under investigation
Product Code: ZED1227 10 mg capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ZED1227
Current Sponsor code: ZED1227
Other descriptive name: Methyl (E,6S)-7-[[1-[2-(2-ethylbutylamino)-2-oxoethyl]-2-oxopyridin-3-yl]amino]-6-[(3-methylimidazole-4-carbonyl)amino]-7-oxohept-2-enoate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use
Product Code: ZED1227 25 mg capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ZED1227
Current Sponsor code: ZED1227
Other descriptive name: Methyl (E,6S)-7-[[1-[2-(2-ethylbutylamino)-2-oxoethyl]-2-oxopyridin-3-yl]amino]-6-[(3-methylimidazole-4-carbonyl)amino]-7-oxohept-2-enoate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use
Product Code: ZED1227 50 mg capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ZED1227
Current Sponsor code: ZED1227
Other descriptive name: Methyl (E,6S)-7-[[1-[2-(2-ethylbutylamino)-2-oxoethyl]-2-oxopyridin-3-yl]amino]-6-[(3-methylimidazole-4-carbonyl)amino]-7-oxohept-2-enoate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use
(ICTRP)
Type of trial
Interventional clinical trial of medicinal product (ICTRP)
Trial design
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4 (ICTRP)
Inclusion/Exclusion criteria
Gender:
Female: yes
Male: yes
Inclusion criteria:
?Documented initial biopsy proven diagnosis of celiac disease 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
?Negative diagnosis of Helicobacter pylori infection
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
(ICTRP)
Exclusion criteria:
?Selective immunoglobulin A deficiency
?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 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
?Severe complications of celiac disease
?Any concomitant diseases of the intestinal tract in addition to celiac disease that might, in the investigator's opinion, interfere with assessment of symptoms of abdominal pain, diarrhea, or other components of celiac disease
?Evidence of relevant systemic disease
Primary and secondary end points
Main Objective: To assess 3 different doses and 2 different dosing schedules of ZED1227 capsules for efficacy in:
- Improvement of the duodenal mucosal morphology as measured by morphometry (VH:CrD), and
- Improvement of celiac disease symptoms assessed by Celiac Disease Symptom Diary (CDSD) in celiac disease subjects experiencing symptoms and having mucosal damage despite gluten-free diet.;Secondary Objective: To assess efficacy of ZED1227 capsules for
? Improvement and changes of duodenal mucosal morphology as measured by morphometry (VH:CrD),
? Improvement and changes of celiac disease symptoms assessed by CDSD,
? Improvement in the Marsh-Oberhuber grouped classes
? Changes of inflammatory cell subsets in duodenal biopsies,
? Changes in serum markers of celiac inflammation,
? Safety and tolerability in terms of adverse events and laboratory parameters,
? Subjects? quality of life.;Primary end point(s): Multi-component endpoint:
-improvement of intestinal mucosal morphology
-improvement in Non-Stool GI Specific Symptom Score OR as an improvement in Diarrhoea Severity Score
;Timepoint(s) of evaluation of this end point: 12 weeks, from Baseline Visit B1 (week 5) to Visit 7 (week 17) (ICTRP)
Secondary end point(s): ? Improvement of intestinal mucosal morphology
? Changes in intestinal mucosal morphology
? Changes in Patient Reported Outcomes (PRO)
? Change in health-related quality of life (EQ-5D-5L)
? Change in serological markers;Timepoint(s) of evaluation of this end point: 12 weeks, from Baseline Visit B1 (week 5) to Visit 7 (week 17) (ICTRP)
Registration date
06.04.2023 (ICTRP)
Incorporation of the first participant
23.02.2023 (ICTRP)
Secondary sponsors
not available
Additional contacts
Dept. of Clinical Research & Develo, mohrbacher@drfalkpharma.de, +497611514156, Dr. Falk Pharma GmbH (ICTRP)
Secondary trial IDs
CEC-4/CEL, 2020-004612-97-FI (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004612-97 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available