Study of DONQ52 in Active Celiac Disease

Official title

A Phase II, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate The Efficacy and Safety of DONQ52 in Active Celiac Disease Patients Who Have Duodenal Mucosal Damage and Persistent Symptoms Despite Attempting A Gluten-free Diet (DAISY STUDY)

Overview

The main aim is to see how DONQ52 works to improve small intestinal damage and reduce celiac-related symptoms due to gluten exposure, in participants with celiac disease (CeD) attempting to maintain a gluten-free diet (GFD) in treated participants versus placebo controls.

Interventions

• Drug Placebo DONQ52
  Placebo DONQ52 subcutaneous injection
• Dietary supplement Simulated Inadvertent Gluten Exposure (SIGE) capsule
  SIGE gluten capsules orally
• Drug DONQ52
  DONQ52 subcutaneous injection
• Dietary supplement Simulated Inadvertent Gluten Exposure (SIGE) capsule
  SIGE gluten capsules orally

Primary outcome measures

• Change in Villous Height to Crypt Depth Ratio (Vh:Cd) [Time frame: Baseline to Week 27]

Secondary outcome measures (8)

• Change in Average of total score of Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) domain (abdominal pain, diarrhea, nausea, and bloating) calculated as two-week average. [Time frame: Baseline to Week 27]
• Change in Average of the total score of non-stool GI symptoms (abdominal pain, nausea, and bloating) calculated as two-week average. [Time frame: Baseline to Week 27]
• Change in Average of diarrhea frequency score as assessed by CDSD frequency supplement calculated as two-week average. [Time frame: Baseline to Week 27]
• Relationship between the total score of CDSD GI domain and Patient Global Impression of Severity (PGI-S) or Patient Global Impression of Change (PGI-C). [Time frame: Baseline to 47 weeks]
• Incidence and severity of adverse events (AEs) and their causal relationship to the investigational medicinal products (IMPs). [Time frame: Baseline to 47 weeks]
• Serum DONQ52 concentration. [Time frame: Day1 to 47 weeks]
• Prevalence of anti-drug antibodies (ADAs) to DONQ52. [Time frame: Day1 to 47 weeks]
• Incidence of anti-drug antibodies (ADAs) to DONQ52. [Time frame: Day1 to 47 weeks]

Eligibility criteria

Inclusion criteria

• Body mass index (BMI) of 18 to 40 (kg/m2) at screening.
• Willingness to ingest a gluten-free product and Simulated Inadvertent Gluten Exposure (SIGE) products as per the study protocol.
• History of medically diagnosed, and adequately documented (i.e., included in the participant's medical records), CeD
• Attempting a GFD for at least 12 months prior to the screening visit.

\- The participants should be instructed not to alter dietary habits including a GFD during the study period.

• Valid results from central testing of blood documenting a positive result for the HLA DQ2.5 genotype (HLA-DQA1\*05 and HLA-DQB1\*02) (homozygous or heterozygous).
• Experienced at least 2 gluten-related symptom events (i.e., 2 different gluten-related symptoms which are diarrhea, abdominal pain, bloating, nausea, tiredness or 1 gluten-related symptom occurred twice) within a month before the screening.
• Willingness to undergo 2 on-study upper gastrointestinal endoscopies with duodenal biopsies.
• Presence of ongoing duodenal mucosal damage defined as Vh:Cd of 2.5 or less

Exclusion criteria

• Participants with documented history (i.e., included in the participant's medical records) of medically diagnosed Refractory Celiac Disease (RCD) or suspected RCD by the investigator.
• History of IgE-mediated reactions to wheat, barley, rye, or other ingredients in gluten-free and SIGE products used in this study (i.e., methylcellulose, and gelatin).
• History of cancer, including hematological malignancy and solid tumors, within 5 years prior to the screening visit, or history of T cell lymphoma or B cell lymphoma ever.
• History of hypersensitivity reactions including anaphylaxis to a biological medical product or any of the excipients.
• Participants who carry the HLA-DQ8 (HLA-DQA1\*03 and DQB1\*0302) genotype (homozygous or heterozygous).
• Any other chronic, active gastrointestinal disease (e.g., inflammatory bowel disease, microscopic colitis, eosinophilic esophagitis, peptic ulcer, gastroesophageal reflux disease, functional dyspepsia, or irritable bowel syndrome) that might in the investigator's opinion, interfere with the assessment of GI symptoms or small intestinal histology.
• Helicobacter pylori tests that indicate current infection.
• Positive either human immunodeficiency virus (HIV) antigen or antibody test at screening.
• Positive hepatitis B surface antigen (HBsAg) test or total hepatitis B core (HBc) antibody test at screening.
• Positive hepatitis C virus (HCV) antibody test at screening, except in participants who have negative results for HCV ribonucleic acid (RNA) test at screening.
• Positive for QuantiFERON-TB Gold test at screening that indicates active tuberculosis (TB) at screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 57 centers

• Pinnacle Research Group, LLC — Anniston
• Birmingham Digestive Health Research — Homewood
• East View Medical Research — Mobile
• Chandler Clinical Trials — Chandler
• Research Solutions of Arizona, PC — Litchfield
• One of a Kind Clinical Research Center LLC — Scottsdale
• Scottsdale Clinical Trials — Scottsdale
• GMC Clinical Research, LLC — Folsom
• … and 49 more centers

New Zealand · 7 centers

• Pacific Clinical Research Network Auckland — Auckland
• CGM Research Trust — Christchurch
• Momentum Clinical Research Dunedin — Dunedin
• Momentum Clinical Research - Pukekohe — Pukekohe
• PCRN Wellington — Upper Hutt
• P3 Research Limited (Wellington) — Wellington
• Pacific Clinical Research Network Hamilton, Waikato — Hamilton

Australia · 6 centers

• Sydney Clinical Trials Pty Ltd — Campbelltown
• Pioneer Clinical Research — North Sydney
• University of the Sunshine Coast Clinical Trials Centre — Morayfield
• University of The Sunshine Coast Clinical Trials Centre (Sippy Downs) — Sippy Downs
• Mater — South Brisbane
• University of the Sunshine Coast Clinical Trials Centre (SouthBank) — South Brisbane

Identifiers

NCT: NCT07239336 · DQB104CT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗