Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease
A Randomized, Double-blind, Placebo-controlled Study of the Safety, Pharmacodynamics, Efficacy, and Pharmacokinetics of TIMP-GLIA in Subjects With Well-controlled Celiac Disease Undergoing Oral Gluten Challenge
1 other identifier
interventional
34
1 country
8
Brief Summary
Subjects enrolled in this study will be evaluated for immune responses and histological changes in the small bowel following 2 doses of TIMP-GLIA or placebo and a 14-day oral gluten challenge.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2018
Shorter than P25 for phase_2
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2018
CompletedStudy Start
First participant enrolled
November 11, 2018
CompletedFirst Posted
Study publicly available on registry
November 13, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 24, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
July 22, 2019
CompletedResults Posted
Study results publicly available
August 12, 2020
CompletedAugust 12, 2020
July 1, 2020
8 months
November 9, 2018
June 22, 2020
July 27, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at Day 20
The spots formed by interferon-gamma-secreting T-cells were counted with an automated ELISPOT analyzer. The average spot-forming units (SFU) per antigen was calculated. A response was considered positive when the average SFU in wells with a given peptide was at least twice that of the average SFU in the no-peptide control wells. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). Peripheral blood mononuclear cell is PBMC.
Baseline (Day 15/Day 1), Day 20
Secondary Outcomes (16)
Change From Baseline in Gliadin-specific T Cell Proliferation by Enzyme-linked Immunosorbent Assay (ELISA) at Day 20
Baseline (Day 15/Day 1), Day 20
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20
Baseline (Day 15/Day 1), Day 20
Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20
Baseline (Day 15/Day 1), Day 20
Change From Baseline in Ratio of Villus Height to Crypt Depth (Vh:Cd) at Day 29
Baseline (Screening), Day 29
Percentage of Participants With Greater Than or Equal to (>=) 0.4 Decrease in Vh:Cd at Day 29
Day 29
- +11 more secondary outcomes
Study Arms (2)
TIMP-GLIA
EXPERIMENTAL8 mg/kg up to a maximum of 650 mg administered intravenously on days 1 and 8.
Placebo
PLACEBO COMPARATORNormal saline administered intravenously on days 1 and 8.
Interventions
Eligibility Criteria
You may qualify if:
- Male or nonpregnant female, ages 18 to 70 years inclusive, at Screening Visit.
- Biopsy-confirmed CD (intestinal histology showing villous atrophy).
- Positive for human leukocyte antigen (HLA)-DQ2 or HLA-DQ2/DQ8 - results will be obtained at Screening if unknown or results are not available.
- Self-reported to be on a GFD for at least 6 months prior to Screening and agree to continue GFD throughout study, with the exception of the oral gluten challenge.
- Normal or negative celiac serology, at screening, defined as:
- Measurable total serum immunoglobulin A (IgA) AND
- Negative or weak positive tissue transglutaminase (tTG) IgA titer OR
- If IgA deficient, defined by a serum IgA level of \< 3 mg/dL, negative or weak positive DGP- IgG titer.
- \. Vh:Cd ≥ 1.5 on screening biopsy.
You may not qualify if:
- Positive for only HLA-DQ8.
- History of clinically confirmed immunoglobulin E (IgE)-mediated reaction and/or anaphylaxis to wheat (i.e., "wheat allergy"), barley or rye.
- Uncontrolled CD and/or active signs/symptoms of CD, in the opinion of the investigator.
- Untreated or active gastrointestinal disease such as peptic ulcer disease, esophagitis (Los Angeles Classification ≥ Grade C), irritable bowel syndrome, inflammatory bowel disease, or microscopic colitis.
- Immunocompromised individuals, including those receiving immunosuppressive doses of corticosteroids (more than 20 mg of prednisone given daily or on alternative days for 2 weeks or more within 6 months prior Dose 1, any dose of corticosteroids within 30 days of Day 1, or high dose inhaled corticosteroids \[\> 960 µg/day of beclomethasone dipropionate or equivalent\]) or other immunosuppressive agents.
- Presence or history of celiac-associated thyroid disease or Type 1 diabetes, regardless of current treatment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
- COUR Pharmaceutical Development Company, Inc.collaborator
Study Sites (8)
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216, United States
Advanced Clinical Research
Meridian, Idaho, 83642, United States
Indianapolis Gastroenterology Research Foundation
Indianapolis, Indiana, 46237, United States
Beth Isreal Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Prism Clinical Research
Saint Paul, Minnesota, 55114, United States
Rapid Medical Research
Beachwood, Ohio, 44122, United States
Advanced Clinical Research
West Jordan, Utah, 84088, United States
Related Publications (1)
Kelly CP, Murray JA, Leffler DA, Getts DR, Bledsoe AC, Smithson G, First MR, Morris A, Boyne M, Elhofy A, Wu TT, Podojil JR, Miller SD; TAK-101 Study Group. TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study. Gastroenterology. 2021 Jul;161(1):66-80.e8. doi: 10.1053/j.gastro.2021.03.014. Epub 2021 Mar 17.
PMID: 33722583DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director Clinical Science
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2018
First Posted
November 13, 2018
Study Start
November 11, 2018
Primary Completion
June 24, 2019
Study Completion
July 22, 2019
Last Updated
August 12, 2020
Results First Posted
August 12, 2020
Record last verified: 2020-07
Data Sharing
- IPD Sharing
- Will share
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.