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.
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 4 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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
intravenous infusion.
Jacksonville Center For Clinical Research
Jacksonville, Florida, United States
Mass General Hospital Translational and Clinical Research Centers
Boston, Massachusetts, United States
Mayo Gastroenterology Research Unit
Rochester, Minnesota, United States
Prism Clinical Research
Saint Paul, Minnesota, United States
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 up to Day 180
Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events
AE Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 4.0. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE. Drug-related adverse events are those that the investigator assessed as possibly or probably related to the study treatment.
Time frame: From Day 1 up to Day 180
Number of Participants With Clinically Significant Physical Examination Findings
Time frame: From Day 1 up to Day 60
Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings
Time frame: From Day 1 up to Day 60
Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels
Time frame: From Day 1 up to Day 60
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
Time frame: From Day 1 up to Day 60
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3
Baseline is defined as Day 1 pre-dose.
Time frame: Baseline (Day 1 pre-dose) and Day 3
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7
Baseline is defined as Day 1 pre-dose.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Baseline (Day 1 pre-dose) and Day 7
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8
Baseline is defined as Day 1 pre-dose.
Time frame: Baseline (Day 1 pre-dose) and Day 8
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10
Baseline is defined as Day 1 pre-dose.
Time frame: Baseline (Day 1 pre-dose) and Day 10
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14
Baseline is defined as Day 1 pre-dose.
Time frame: Baseline (Day 1 pre-dose) and Day 14
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38
Baseline is defined as Day 1 pre-dose.
Time frame: Baseline (Day 1 pre-dose) and Day 38
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60
Baseline is defined as Day 1 pre-dose.
Time frame: Baseline (Day 1 pre-dose) and Day 60
Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1
Baseline was defined as Day 1 Pre-dose.
Time frame: Baseline (Day 1 pre-dose) and 15 minutes (min) post-dose on Day 1
Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1
Baseline was defined as Day 1 Pre-dose.
Time frame: Baseline (Day 1 pre-dose) and 30 min post-dose on Day 1
Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2
Baseline was defined as Day 1 Pre-dose.
Time frame: Baseline (Day 1 pre-dose) and Day 2
Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis
Time frame: From Day 1 up to Day 60
Part A (Greater Than or Equal to [>=] 4.0 mg/kg) and Part B: Number of Participants With Clinically Significant Change From Baseline in Gliadin-Specific T-cell Proliferation and Cytokine Release Markers
Time frame: Part A (>=4.0 mg/kg): Day 1 pre-dose up to 144 hours post-dose on Day 7; Part B: Day 8 pre-dose up to 144 hours post-dose on Day 14
Number of Participants With Clinically Significant Laboratory Abnormalities
Time frame: From Day 1 up to Day 60
Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose