Study of the safety, pharmacokinetics, immunogenicity, and biological effects of DONQ52 in celiac disease patients with gluten challenge
- Conditions
- Celiac diseaseOral and Gastrointestinal - Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
- Registration Number
- ACTRN12624000316505
- Lead Sponsor
- Chugai Pharmaceutical Co., Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 56
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)
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence of adverse events (AEs)[National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v5.0) Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal];Severity of AEs[National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v5.0) Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal];Vital signs [Respiratory rate, pulse rate, systolic and diastolic blood pressure and body temperature as per sites standard practice. <br>Peripheral oxygen [SpO2] will be measured using an oximeter. Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal]
- Secondary Outcome Measures
Name Time Method