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Study of the Safety, Tolerability and Pharmacokinetics of TIMP-GLIA in Subjects With Celiac Disease

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ClinicalTrials.gov Identifier: NCT03486990
Recruitment Status : Active, not recruiting
First Posted : April 3, 2018
Last Update Posted : November 12, 2018
Sponsor:
Information provided by (Responsible Party):
COUR Pharmaceutical Development Company, Inc.

Brief Summary:
This study is to characterize the safety and tolerability of an investigational drug called TIMP-GLIA when either one or two intravenous doses are given to subjects with celiac disease. The way the body reacts to TIMP-GLIA is being checked by laboratory tests of the blood and urine, and study participant health will also be monitored by vital signs such as blood pressure, electrocardiogram (ECG), and physical examination.

Condition or disease Intervention/treatment Phase
Celiac Disease Drug: TIMP-GLIA Phase 1

Detailed Description:

This study is a 2-part, multicenter study. In Part A, eligible subjects will be enrolled into escalating dose cohorts (n = 2/cohort for 2 dose levels followed by n = 3/cohort for 5 dose levels). TIMP-GLIA will be administered as a single intravenous (IV) infusion on Day 1. A staggered dosing strategy will be used in Part A. Subjects will undergo medical observation in the clinic for at least 48 hours after dosing and participate in outpatient follow-up visits. Adverse events (AEs), vital signs, and electrocardiograms (ECGs) and laboratory data (serum chemistry, coagulation, hematology and urinalysis, cytokines) will be assessed by a Safety Committee before the next cohort will be dosed at a higher dose level.

After completion of Part A and confirmation by the Safety Committee to proceed, eligible subjects (n=3) will receive two IV infusions of TIMP-GLIA, 7 days apart, on Day 1 and on Day 8. Each subject in Part B will be observed in clinic for 48 hours after each dose and undergo similar testing and follow-up visits as in Part A.

The safety and pharmacokinetic profile of TIMP-GLIA will be characterized.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Single ascending dose followed by repeat dose
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-Human, 2-Part, Multicenter Dose Escalation and Repeat Dose Study of the Safety, Tolerability and Pharmacokinetics of TIMP-GLIA in Subjects With Celiac Disease
Actual Study Start Date : February 9, 2018
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

Arm Intervention/treatment
Experimental: Cohort 1
0.1 mg/kg, single IV infusion TIMP-GLIA
Drug: TIMP-GLIA
intravenous infusion

Experimental: Cohort 2
0.5 mg/kg, single IV infusion TIMP-GLIA
Drug: TIMP-GLIA
intravenous infusion

Experimental: Cohort 3
1 mg/kg, single IV infusion TIMP-GLIA
Drug: TIMP-GLIA
intravenous infusion

Experimental: Cohort 4
2 mg/kg, single IV infusion TIMP-GLIA
Drug: TIMP-GLIA
intravenous infusion

Experimental: Cohort 5
4 mg/kg, single IV infusion TIMP-GLIA
Drug: TIMP-GLIA
intravenous infusion

Experimental: Cohort 6
8 mg/kg, single IV infusion TIMP-GLIA
Drug: TIMP-GLIA
intravenous infusion

Experimental: Cohort 7
10 mg/kg, single IV infusion TIMP-GLIA
Drug: TIMP-GLIA
intravenous infusion

Experimental: Cohort 8
Repeat dose, two IV infusions TIMP-GLIA, dose level to be determined
Drug: TIMP-GLIA
intravenous infusion




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 as a Measure of Safety and Tolerability of TIMP-GLIA [ Time Frame: Through study day 180 ]
    An adverse event is any untoward medical occurrence in a participant who received study drug without regard to possibility of a causal relationship to the study drug.


Secondary Outcome Measures :
  1. Pharmacokinetics of TIMP-GLIA in plasma: Cmax [ Time Frame: Through to 144 hours post dose ]
    Maximum observed concentration (Cmax) after dosing

  2. Pharmacokinetics of TIMP-GLIA in plasma: Tmax [ Time Frame: Through 144 hours post dose ]
    The time after dosing when Cmax is observed (Tmax)

  3. Pharmacokinetics of TIMP-GLIA in plasma: Clast [ Time Frame: Through 144 hours post dose ]
    Last measurable concentration (Clast) after dosing

  4. Pharmacokinetics of TIMP-GLIA in plasma: Tlast [ Time Frame: Through 144 hours post dose ]
    The time after dosing when the last measurable concentration is observed (Tlast)

  5. Pharmacokinetics of TIMP-GLIA in plasma: AUClast [ Time Frame: Through 144 hours post dose ]
    Area under the TIMP-GLIA concentration-time curve from time zero to last measurable concentration (AUClast)

  6. Pharmacokinetics of TIMP-GLIA in plasma: AUCinf [ Time Frame: Through 144 hours post dose ]
    Area under the TIMP-GLIA concentration-time curve from time zero extrapolated to infinity (AUCinf)

  7. Pharmacokinetics of TIMP-GLIA in plasma: t1/2 [ Time Frame: Through 144 hours post dose ]
    Apparent Terminal Elimination Half-life (t1/2)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject provides written informed consent and is willing and able to comply with study requirements.
  • At screening the subject has a minimum body mass index (BMI) of 16 kg/m2 and a minimum body weight of 33 kg up to a maximum body weight of 129 kg, inclusive. If subject is considered to be underweight or overweight/obese, the subject is otherwise healthy in the opinion of the investigator.
  • The subject has celiac disease characterized at Screening Visit by:

    • a history of biopsy-confirmed celiac disease; and
    • no known gluten exposure for at least 10 days; and
    • willingness to maintain a gluten-free diet for the duration of the study; and
    • a negative or weak positive transglutaminase (tTG)-specific IgA titer if the subject has a normal total immunoglobulin A (IgA) titer or has a partial IgA deficiency OR
    • a negative or weak positive deamidated gliadin peptide (DGP)-specific immunoglobulin G (IgG) titer if the subject has IgA deficiency.
  • The male subject or female subject of childbearing potential will practice medically approved contraception during the study.

Exclusion Criteria:

  • The subject has a history of clinically confirmed immunoglobulin E-mediated reaction and/or anaphylaxis to wheat (i.e., "wheat allergy"), barley or rye.
  • The subject has a known history of hypersensitivity or allergies to TIMP-GLIA components OR any other known severe hypersensitivity or allergic reaction (resulted in hospitalization [initial or prolonged], congenital anomaly, or disability, or that required medical intervention to prevent permanent impairment or damage) to any other allergens (medications, food or environmental).
  • The subject has uncontrolled celiac disease and/or complications of celiac disease, or otherwise has experienced celiac symptomology within 10 days of screening, in the opinion of the investigator.
  • The subject has a history of, or has an active, significant, clinically relevant, comorbidity (including Type 1 and Type 2 diabetes mellitus and other autoimmune disorders, splenectomy) that, in the opinion of the investigator, would make the subject unsuitable for participation in the study and/or could adversely affect interpretation of the study results.
  • The subject has had significant changes to or anticipates changes to prescription or non-prescription medication used to manage an underlying comorbidity within 30 days prior to first dosing (Day 1).
  • The subject is currently taking or received systemic biologics 6 months prior to first dosing (Day 1).
  • The subject has a compromised immune system, e.g.

    • known human immunodeficiency virus (HIV) infection or positive for HIV antibodies at Screening or
    • immunosuppressive medical treatment taken during the 2 months prior to first dosing (Day 1) or
    • immunosuppressive doses of corticosteroids (more than 20 mg of prednisone given daily for 2 weeks or more within 2 months prior to first dosing (Day 1), or any dose of corticosteroids within 30 days of first dosing (Day 1), or high dose inhaled corticosteroids [>960 µg/day of beclomethasone dipropionate or equivalent]) within 30 days of first dosing Day 1.
  • The subject has currently 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.
  • The subject has an active malignancy, or history of malignancy or chemotherapy, within the past 5 years other than history of localized or surgical removal of focal basal cell skin cancer, cervical cancer in situ treated successfully in the past by local treatment (including but not limited to cryotherapy or laser therapy) or by hysterectomy.
  • The subject has known liver disease or serology positive for hepatitis C infection; positive hepatitis B surface antigen (HBsAg) at Screening Visit.
  • The subject has a positive test result for drugs of abuse, cannabinoids, or alcohol at Screening Visit or at Check-in.
  • The subject has a history of any drug or alcohol abuse in the past 5 years or alcohol consumption habits that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements.
  • The subject has clinically significant laboratory test results (e.g., liver tests) or electrocardiogram (EGC) abnormalities (e.g., cardiac conduction abnormalities) at Screening
  • The subject received a live or inactive vaccine within 28 days prior or a subunit vaccine within 14 days prior to first dosing/Day 1 or the subject has a planned vaccination during the study.

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): NCT03486990


Locations
United States, Florida
Jacksonville Center For Clinical Research
Jacksonville, Florida, United States, 32216
United States, Massachusetts
Mass General Hospital Translational and Clinical Research Centers
Boston, Massachusetts, United States, 02114
United States, Minnesota
Mayo Gastroenterology Research Unit
Rochester, Minnesota, United States, 55905
Prism Clinical Research
Saint Paul, Minnesota, United States, 55114
Sponsors and Collaborators
COUR Pharmaceutical Development Company, Inc.
Investigators
Study Chair: Ciaran P Kelly, MD Beth Israel Deaconess Medical Center, Dept Gastroenterology

Responsible Party: COUR Pharmaceutical Development Company, Inc.
ClinicalTrials.gov Identifier: NCT03486990     History of Changes
Other Study ID Numbers: TGLIA-5.001
First Posted: April 3, 2018    Key Record Dates
Last Update Posted: November 12, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by COUR Pharmaceutical Development Company, Inc.:
safety
tolerability
pharmacokinetics
celiac
gliadin
gluten

Additional relevant MeSH terms:
Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases