None listed
Conditions
Brief summary
This randomized, double-blind, placebo-controlled, multicenter study aims to evaluate the effects of DONQ52 in CeD patients when they are given a gluten challenge. DONQ52 is expected to be a safe and effective treatment for CeD patients. This study consists of a part of gluten challenge for HLA-DQ2.5 genotype (without HLA-DQ2.2 and/or HLA-DQ8) (Part A) and for atypical HLA-DQ genotype (HLA-DQ2.2 and/or HLA-DQ8 in the absence or the presence of HLA-DQ2.5) (Part B). All parts of this study are designed to investigate a single subcutaneous (SC) dose of DONQ52 with a 3-day gluten challenge in well-controlled CeD patients. All participants must maintain a gluten-free diet (GFD) throughout the study (by the study completion/early termination visit) except for the instructed and controlled gluten challenge.
Interventions
DONQ52 at 2.0 mg/kg or placebo (at corresponding volume) will be administered subcutaneously on the first day only. In addition to the first day of administration, participants also visit the clinical site on an outpatient basis in day 4, day 9, day 14, day 22, day 29, day 43, day 64, day 92, day 120, day 148, and the last visit on day 176. The participants will be given 10 g of gluten challenge materials from Day 9 (8 days after the first DONQ52/placebo administration) to Day 11, which means th
DONQ52 at 2.0 mg/kg or placebo (at corresponding volume) will be administered subcutaneously on the first day only. In addition to the first day of administration, participants also visit the clinical site on an outpatient basis in day 4, day 9, day 14, day 22, day 29, day 43, day 64, day 92, day 120, day 148, and the last visit on day 176. The participants will be given 10 g of gluten challenge materials from Day 9 (8 days after the first DONQ52/placebo administration) to Day 11, which means the participants will take up to 30 g of gluten in total. Participants will consume gluten materials that is mixed with chocolate milk. All participants must maintain a gluten-free diet (GFD) throughout the study except for the instructed gluten challenge. This study consists of a part of gluten challenge for HLA-DQ2.5 genotype (without HLA-DQ2.2 and/or HLA-DQ8) (Part A) and for atypical HLA-DQ genotype (HLA-DQ2.2 and/or HLA-DQ8 in the absence or the presence of HLA-DQ2.5) (Part B). Parts A and B will complete the same study procedures in parallel (with the exception that blood collection for ELISpot and Tetramer are not included for Part B). Parts A and B will be analyzed separately. No comparison will be made in the analysis..
Sponsors
Chugai Pharmaceutical Co., Ltd
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria for all Parts 1) Age 18–70 years 2) Body mass index (BMI) of 18 to 35 (kg/m2) 3) History of medically diagnosed CeD 4) Be on a GFD for at least 12 months 5) For women of childbearing potential: agreement to remain abstinent or use effective methods of contraception 6) Experienced at most mild symptoms of CeD within a month before the screening visit 7) Willingness to consume food containing up to 10 g /day of wheat gluten per challenge day and up to 30 g of wheat gluten in total during the study Inclusion Criteria for Part A 8) Positive for the human leukocyte antigen (HLA)-DQ2.5 genotype (HLA-DQA1*05 and HLA-DQB1*02) (homozygous or heterozygous) Inclusion Criteria for Part B 9) Positive for HLA-DQ8 genotype (HLA-DQA1*03 and DQB1*0302) or HLA-DQ2.2 genotype (HLA-DQA1*0201 and HLA-DQB1*02) (homozygous or heterozygous)
Exclusion criteria
Participants who meet any of the following criteria will be excluded from all Parts of study entry: Exclusion Criteria for Medical History 1) Refractory CeD defined as persistent or recurrent malabsorptive symptoms and signs with villous atrophy (Marsh grade 3) despite a strict GFD for more than 12 months 2) Participation in an investigational study involving non-biological therapy within 30 days or 5 half-lives of the investigational product (whichever is greater) prior to the screening visit 3) Participation in an investigational study involving biological therapy (including vaccines) within 90 days or 5 half-lives of the investigational product (whichever is greater) prior to the screening visit unless they are known to have only received placebo 4) Participation in immune tolerance study where they received an immune-tolerogenic agent for CeD within 12 months prior to the screening visit 5) History of hypersensitivity reactions including anaphylaxis to a biological medical product or any of the excipients 6) History of immunoglobulin E (IgE)-mediated reactions to wheat, barley, rye, or other ingredients in the gluten products used in the study 7) History of gluten ataxia, or peripheral neuropathy 8) History of dermatitis herpetiformis 9) History of severe or prolonged reactions (>72 hours) with exposure to gluten. 10) History of cancer, including hematologic malignancy and solid tumors, within 5 years prior to the screening visit Exclusion Criteria for Complications 11) Any known active infection (with the exception of fungal nail infections or oral herpes) 12) Any uncontrolled complications of CeD (e.g., enteropathy-associated T cell lymphoma, ulcerative jejunitis, intestinal perforation) or any uncontrolled other autoimmune diseases 13) Any other chronic, active gastrointestinal disease (e.g., inflammatory bowel disease, microscopic colitis, peptic ulcer, gastroesophageal reflux disease, functional dyspepsia, or irritable bowel syndrome) Exclusion Criteria for Screening Measurements 14) Participants who carry the specific HLA-DQ genotype, as described below: - For Part A; HLA-DQ8 (HLA-DQA1*03 and DQB1*0302) or HLA-DQ2.2 (HLA-DQA1*0201 and HLA-DQB1*02) in the absence or the presence of HLA-DQ2.5 (HLA-DQA1*05 and DQB1*02) 15) Positive for any of the following 3 serology tests, tTG2-IgA, DGP-IgA, and DGP-IgG, within the month before screening or during the screening period: Exclusion Criteria for Concomitant Medications 16) Use of immune checkpoint inhibitors (e.g., ipilimumab) within 60 months prior to the screening visit 17) Use of agents that deplete B or T cells (e.g., rituximab, alemtuzumab, visilizumab, or ocrelizumab) within 60 months prior to the screening visit 18) Use of immunomodulatory or immune-suppressing medical treatment during the 6 months prior to the screening visit (e.g., azathioprine, methotrexate, Jak inhibitors, or biologics) 19) Use of oral or parenteral corticosteroids within 4 weeks prior to the screening visit - Topical or inhaled corticosteroids are acceptable. 20) Chronic nonsteroidal anti-inflammatory drugs (NSAIDs) use Exclusion Criteria for Overall Participant Conditions 21) Pregnant or lactating women 22) Any medical condition that, in the opinion of the investigator, would impact the immune response (other than CeD), confound interpretation of study results, or pose an increased risk to the participant
Outcome results
None listed