Study of the Safety, Tolerability and Pharmacokinetics of TIMP-GLIA in Subjects With Celiac Disease
Condition: Celiac Disease
MeSH terms: Celiac Disease
Intervention: TIMP-GLIA
Intervention description: intravenous infusion.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Single ascending dose followed by repeat dose.
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: safety; tolerability; pharmacokinetics; celiac; gliadin; gluten

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 subject health will also be monitored by vital signs such as blood pressure,
      electrocardiogram (ECG), and physical examination.
    

Eligibility 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.