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Trial registered on ANZCTR


Registration number
ACTRN12624000316505
Ethics application status
Approved
Date submitted
14/02/2024
Date registered
25/03/2024
Date last updated
19/10/2024
Date data sharing statement initially provided
25/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of the safety, pharmacokinetics, immunogenicity, and biological effects of DONQ52 in celiac disease patients with gluten challenge
Scientific title
A phase IC, randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety, pharmacokinetics, immunogenicity, and biological effects of DONQ52 in celiac disease patients with gluten challenge
Secondary ID [1] 311510 0
DQB103CT
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Celiac disease 332837 0
Condition category
Condition code
Oral and Gastrointestinal 329563 329563 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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..
Intervention code [1] 327965 0
Treatment: Drugs
Comparator / control treatment
Excipient formulation (L-histidine, L-arginine, L-aspartic acid, L-methionine and polysorbate 80)
Control group
Placebo

Outcomes
Primary outcome [1] 337355 0
Incidence of adverse events (AEs)
Timepoint [1] 337355 0
Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal
Primary outcome [2] 337356 0
Severity of AEs
Timepoint [2] 337356 0
Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal
Primary outcome [3] 337607 0
Vital signs
Timepoint [3] 337607 0
Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal
Secondary outcome [1] 432505 0
Clinical laboratory test results (primary outcome)
Timepoint [1] 432505 0
Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal
Secondary outcome [2] 432507 0
12-lead electrocardiograms (primary outcome)
Timepoint [2] 432507 0
Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal
Secondary outcome [3] 432511 0
Serum DONQ52 concentration
Timepoint [3] 432511 0
Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal
Secondary outcome [4] 432512 0
PK parameters of DONQ52
Timepoint [4] 432512 0
Screening, treatment day 1, 4, 9, 14, 22, 29, follow-up day 43, 64, 92, 120, 148, study completion / withdrawal
Secondary outcome [5] 432513 0
Prevalence of anti-drug antibodies (ADA)s to DONQ52
Timepoint [5] 432513 0
Screening, treatment day 29, study completion / withdrawal
Secondary outcome [6] 432514 0
Incidence of anti-drug antibodies (ADA)s to DONQ52
Timepoint [6] 432514 0
Screening, treatment day 29, study completion / withdrawal
Secondary outcome [7] 432515 0
Change from baseline in the level of interleukin-2 (IL-2) evaluated by ultrasensitive immunoassay
Timepoint [7] 432515 0
Cytokine (IL-2) is measured at Day 1 prior to the IMP administration, Day 4 (at any time) and Day 9 before gluten challenge, at 2, 4, 6-hour after gluten challenge
Secondary outcome [8] 432516 0
Change from baseline in gluten-specific T cell interferon gamma production (as measured by spot forming unit [SFU])
Timepoint [8] 432516 0
Treatment day 9, 14

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/05/2024
Actual
16/07/2024
Date of last participant enrolment
Anticipated
20/08/2025
Actual
Date of last data collection
Anticipated
17/02/2026
Actual
Sample size
Target
56
Accrual to date
22
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment outside Australia
Country [1] 26298 0
New Zealand
State/province [1] 26298 0
Wellington, Auckland, Dunedin, Palmerston North, Hastings

Funding & Sponsors
Funding source category [1] 315787 0
Commercial sector/Industry
Name [1] 315787 0
Chugai Pharmaceutical Co., Ltd
Country [1] 315787 0
Japan
Primary sponsor type
Commercial sector/Industry
Name
Chugai Pharmaceutical Co., Ltd
Address
Country
Japan
Secondary sponsor category [1] 317913 0
None
Name [1] 317913 0
Address [1] 317913 0
Country [1] 317913 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314647 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 314647 0
https://www.thermh.org.au/research/researchers/ethics
Ethics committee country [1] 314647 0
Australia
Date submitted for ethics approval [1] 314647 0
24/10/2023
Approval date [1] 314647 0
10/01/2024
Ethics approval number [1] 314647 0
2023.251
Ethics committee name [2] 314659 0
Bellberry Human Research Ethics Committee L
Ethics committee address [2] 314659 0
https://bellberry.com.au/
Ethics committee country [2] 314659 0
Australia
Date submitted for ethics approval [2] 314659 0
18/10/2023
Approval date [2] 314659 0
12/12/2023
Ethics approval number [2] 314659 0
2023-09-1198
Ethics committee name [3] 315282 0
Northern A Health and Disability Ethics Committee 
Ethics committee address [3] 315282 0
https://ethics.health.govt.nz/about/northern-a-health-and-disability-ethics-committee/
Ethics committee country [3] 315282 0
New Zealand
Date submitted for ethics approval [3] 315282 0
02/04/2024
Approval date [3] 315282 0
05/07/2024
Ethics approval number [3] 315282 0
2024 FULL 19940

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132270 0
A/Prof Jason Tye-Din
Address 132270 0
The Royal Melbourne Hospital. 300 Grattan Street, Parkville VIC, 3050
Country 132270 0
Australia
Phone 132270 0
+61 3 9345 2533
Fax 132270 0
Email 132270 0
[email protected]
Contact person for public queries
Name 132271 0
Yosuke Murakami
Address 132271 0
Chugai Pharmaceutical Co., Ltd, 2-1-1, Nihonbashimuromachi, Chuo-ku, Tokyo
Country 132271 0
Japan
Phone 132271 0
+81 3 3281 6611
Fax 132271 0
Email 132271 0
[email protected]
Contact person for scientific queries
Name 132272 0
Yosuke Murakami
Address 132272 0
Chugai Pharmaceutical Co., Ltd. 2-1-1, Nihonbashimuromachi, Chuo-ku, Tokyo
Country 132272 0
Japan
Phone 132272 0
+81 3 3281 6611
Fax 132272 0
Email 132272 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.