- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03738475
Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease
July 27, 2020 updated by: Takeda
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
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.
Study Overview
Detailed Description
This study is a randomized, double-blind, placebo-controlled clinical trial to assess the safety, pharmacodynamics, efficacy, and PK, of TIMP-GLIA in subjects with well-controlled celiac disease (CD) following an oral gluten challenge.
Subjects aged 18 to 70 years inclusive, with documented history of biopsy-proven confirmed CD, and on a gluten-free diet (GFD) for a minimum of 6 months, will be screened.
Subjects who meet all inclusion and no exclusion criteria, and provide written informed consent, will be randomized within 45 days after Screening to receive 2 intravenous (IV) infusions of TIMP-GLIA, 8 mg/kg up to a maximum of 650 mg or placebo (normal saline) in a 1:1 ratio.
Treatment with drug or placebo will be followed by 14 days gluten challenge.
Study Type
Interventional
Enrollment (Actual)
34
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Jacksonville, Florida, United States, 32216
- Jacksonville Center for Clinical Research
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Idaho
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Meridian, Idaho, United States, 83642
- Advanced Clinical Research
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Indiana
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Indianapolis, Indiana, United States, 46237
- Indianapolis Gastroenterology Research Foundation
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Isreal Deaconess Medical Center
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Saint Paul, Minnesota, United States, 55114
- Prism Clinical Research
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Ohio
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Beachwood, Ohio, United States, 44122
- Rapid Medical Research
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Utah
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West Jordan, Utah, United States, 84088
- Advanced Clinical Research
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Key Inclusion Criteria:
- 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.
6. Vh:Cd ≥ 1.5 on screening biopsy.
Key Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: TIMP-GLIA
8 mg/kg up to a maximum of 650 mg administered intravenously on days 1 and 8.
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8 mg/kg up to a maximum of 650 mg administered intravenously on days 1 and 8.
Other Names:
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Placebo Comparator: Placebo
Normal saline administered intravenously on days 1 and 8.
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Administered intravenously on days 1 and 8.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at Day 20
Time Frame: Baseline (Day 15/Day 1), Day 20
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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.
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Baseline (Day 15/Day 1), Day 20
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Gliadin-specific T Cell Proliferation by Enzyme-linked Immunosorbent Assay (ELISA) at Day 20
Time Frame: Baseline (Day 15/Day 1), Day 20
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Gliadin-specific T cell proliferation was determined by ELISA test.
Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15).
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Baseline (Day 15/Day 1), Day 20
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Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20
Time Frame: Baseline (Day 15/Day 1), Day 20
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Gliadin-specific T Cell cytokine secretion was determined by ELISA test.
Gliadin-specific cytokine included interferon gamma (IFN-γ), interleukin (IL) 1-beta (1-β), IL-10, IL-12, IL-13, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor alpha (TNF-α).
Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15).
A negative change from baseline value was reported when the observed sample response was less than the observed background response.
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Baseline (Day 15/Day 1), Day 20
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Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20
Time Frame: Baseline (Day 15/Day 1), Day 20
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Change from baseline value for Gut-Homing cells like CD4, CD8 and Gamma Delta T-cells were reported.
Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15).
Phenotype (unique cell population) for CD8 cell is EM CD8 > aE+b7hi > aE+b7hiCD38+, for CD4 is EM Th > a4+b7hi > a4+b7hiCD38+ and for Gamma Delta T-cells is TCRgd T cells > aE+b7hi > aE+b7hiCD38+ in this outcome measure.
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Baseline (Day 15/Day 1), Day 20
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Change From Baseline in Ratio of Villus Height to Crypt Depth (Vh:Cd) at Day 29
Time Frame: Baseline (Screening), Day 29
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Attenuation of the effects of gluten exposure was assessed by measuring the change from baseline in villous height (Vh) to crypt depth (Cd) ratio after 29 days of gluten challenge.
Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CD.
Crypts are grooves between the villi that are often elongated in participants with CD.
A decreased Vh:Cd ratio indicates worsening disease.
Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1.
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Baseline (Screening), Day 29
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Percentage of Participants With Greater Than or Equal to (>=) 0.4 Decrease in Vh:Cd at Day 29
Time Frame: Day 29
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Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CD.
Crypts are grooves between the villi that are often elongated in participants with CD.
A decreased Vh:Cd ratio indicates worsening disease.
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Day 29
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Change From Baseline in Number of Intestinal Intraepithelial Lymphocytes (IELs) at Day 29
Time Frame: Baseline (Screening), Day 29
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IELs were white blood cells interspersed between epithelial cells of the small and large intestine where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen or immune-induced pathology.
Increased intraepithelial lymphocytes was associated with celiac disease.
Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1.
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Baseline (Screening), Day 29
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Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment
Time Frame: Days 15, 20, 29 and 35
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The CSI were clinically oriented, easily administered, questionnaires with 16 items.
The modified CSI (6-items) was derived from a subset of questions from the CSI questionnaire, including the diarrhea, nausea, rumbling in stomach, stomach felt bloated, diarrhea and low energy level abdominal pain domains (a total of 6 questions), which were each assessed on a scale of 1 to 5- none of the time, a little of the time, some of the time, most of the time and all of the time respectively.
Higher CSI scores correlate with more severe CD symptoms.
It is to be used to assess symptoms before, during, and after the oral gluten challenge.
Here D refers to Day.
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Days 15, 20, 29 and 35
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Plasma Concentrations of TIMP-GLIA
Time Frame: Day 8: 0 hours (pre-infusion), end of infusion, and at 2 hours post-infusion
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Day 8: 0 hours (pre-infusion), end of infusion, and at 2 hours post-infusion
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Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Time Frame: From the first dose of study drug up to Day 35
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From the first dose of study drug up to Day 35
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Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time Frame: From the first dose of study drug up to Day 35
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From the first dose of study drug up to Day 35
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Number of Participants With Clinically Significant Change From Baseline in Hematology or Serum Chemistry Laboratory Values
Time Frame: From the first dose of study drug up to Day 35
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From the first dose of study drug up to Day 35
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Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35
Time Frame: Baseline (Screening), Days 8, 15, 20, 29, and 35
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Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1.
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Baseline (Screening), Days 8, 15, 20, 29, and 35
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Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15
Time Frame: Baseline (Day 1), Days 2, 8, 9, and 15
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Baseline was defined as the pre-dose value on Day 1.
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Baseline (Day 1), Days 2, 8, 9, and 15
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Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15
Time Frame: Baseline (Day 1) , Days 2, 8, 9, and 15
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Baseline was defined as the pre-dose value on Day 1.
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Baseline (Day 1) , Days 2, 8, 9, and 15
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Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35
Time Frame: Baseline (Day 1), Days 15, 20, 29, and 35
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Baseline was defined as the pre-dose value on Day 1.
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Baseline (Day 1), Days 15, 20, 29, and 35
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Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15
Time Frame: Baseline (Day 1), Days 2, 8, 9, and 15
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Baseline was defined as Day 1 pre-dose.
A negative change from baseline value was reported when the observed sample response was less than the observed background response.
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Baseline (Day 1), Days 2, 8, 9, and 15
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 11, 2018
Primary Completion (Actual)
June 24, 2019
Study Completion (Actual)
July 22, 2019
Study Registration Dates
First Submitted
November 9, 2018
First Submitted That Met QC Criteria
November 9, 2018
First Posted (Actual)
November 13, 2018
Study Record Updates
Last Update Posted (Actual)
August 12, 2020
Last Update Submitted That Met QC Criteria
July 27, 2020
Last Verified
July 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TGLIA-5.002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
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.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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