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Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03738475
Recruitment Status : Active, not recruiting
First Posted : November 12, 2018
Last Update Posted : June 19, 2019
Sponsor:
Information provided by (Responsible Party):
COUR Pharmaceutical Development Company, Inc.

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.

Condition or disease Intervention/treatment Phase
Celiac Disease Drug: TIMP-GLIA Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized double-blind placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-Blind
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 4, 2019
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

Arm Intervention/treatment
Experimental: TIMP-GLIA
8 mg/kg up to a maximum of 650 mg administered intravenously on days 1 and 8
Drug: TIMP-GLIA
8 mg/kg up to a maximum of 650 mg administered intravenously on days 1 and 8

Placebo Comparator: Placebo
Normal saline administered intravenously on days 1 and 8
Drug: Placebo
Administered intravenously on days 1 and 8
Other Name: 0.9% sodium chloride (normal saline)




Primary Outcome Measures :
  1. IFN-γ spot forming units [ Time Frame: 6 days ]
    Change from baseline in IFN-γ spot forming units following oral gluten challenge


Secondary Outcome Measures :
  1. IFN-γ spot forming units [ Time Frame: 6 days ]
    Proportion of subjects with 3-fold increase from baseline following oral gluten challenge

  2. Villus height to crypt depth ratio (Vh:Cd) [ Time Frame: 29 days ]
    Change from baseline in Vh:Cd following oral gluten challenge

  3. Villus height to crypt depth ratio (Vh:Cd) [ Time Frame: 29 days ]
    Proportion of subjects with ≥ 0.4 decrease in Vh:Cd following oral gluten challenge

  4. Intestinal intraepithelial lymphocytes (IELs) [ Time Frame: 29 days ]
    Change from baseline in number of IELs following oral gluten challenge

  5. Gliadin-specific T cell proliferation [ Time Frame: 15 days ]
    Change from baseline in gliadin-specific T cell proliferation

  6. Gliadin-specific cytokine secretion [ Time Frame: 15 days ]
    Change from baseline in gliadin-specific cytokine secretion

  7. Gut-homing CD4, CD8, and γδ cells [ Time Frame: 6 days ]
    Change from baseline in number of gut-homing CD4, CD8, and γδ cells following oral gluten challenge

  8. Adverse Events [ Time Frame: 35 days ]
    Frequency of adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Male or nonpregnant female, ages 18 to 70 years inclusive, at Screening Visit.
  2. Biopsy-confirmed CD (intestinal histology showing villous atrophy).
  3. Positive for human leukocyte antigen (HLA)-DQ2 or HLA-DQ2/DQ8 - results will be obtained at Screening if unknown or results are not available.
  4. 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.
  5. Normal or negative celiac serology, at screening, defined as:

    1. Measurable total serum immunoglobulin A (IgA) AND
    2. Negative or weak positive tissue transglutaminase (tTG) IgA titer OR
    3. 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:

  1. Positive for only HLA-DQ8.
  2. History of clinically confirmed immunoglobulin E (IgE)-mediated reaction and/or anaphylaxis to wheat (i.e., "wheat allergy"), barley or rye.
  3. Uncontrolled CD and/or active signs/symptoms of CD, in the opinion of the investigator.
  4. 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.
  5. 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.
  6. Presence or history of celiac-associated thyroid disease or Type 1 diabetes, regardless of current treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03738475


Locations
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United States, Florida
Jacksonville Center for Clinical Research
Jacksonville, Florida, United States, 32216
United States, Idaho
Advanced Clinical Research
Meridian, Idaho, United States, 83642
United States, Indiana
Indianapolis Gastroenterology Research Foundation
Indianapolis, Indiana, United States, 46237
United States, Massachusetts
Beth Isreal Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Clinical Research Institute of Michigan
Chesterfield, Michigan, United States, 48047
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Prism Clinical Research
Saint Paul, Minnesota, United States, 55114
United States, Ohio
Rapid Medical Research
Beachwood, Ohio, United States, 44122
United States, Utah
Advanced Clinical Research
West Jordan, Utah, United States, 84088
Sponsors and Collaborators
COUR Pharmaceutical Development Company, Inc.

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Responsible Party: COUR Pharmaceutical Development Company, Inc.
ClinicalTrials.gov Identifier: NCT03738475     History of Changes
Other Study ID Numbers: TGLIA-5.002
First Posted: November 12, 2018    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases
Tissue Inhibitor of Metalloproteinases
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action