Celiac Disease
Conditions
Keywords
safety, tolerability, pharmacokinetics, celiac, gliadin, gluten
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 subject health will also be monitored by vital signs such as blood pressure, electrocardiogram (ECG), and physical examination.
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 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.
Interventions
DRUGTIMP-GLIA
intravenous infusion.
Sponsors
COUR Pharmaceutical Development Company, Inc.
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single ascending dose followed by repeat dose.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Laboratory Abnormalities | From Day 1 up to Day 60 | — |
| Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38 | Baseline (Day 1 pre-dose) and Day 38 | Baseline is defined as Day 1 pre-dose. |
| Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60 | Baseline (Day 1 pre-dose) and Day 60 | Baseline is defined as Day 1 pre-dose. |
| Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose) and 15 minutes (min) post-dose on Day 1 | Baseline was defined as Day 1 Pre-dose. |
| Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose) and 30 min post-dose on Day 1 | Baseline was defined as Day 1 Pre-dose. |
| Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Baseline (Day 1 pre-dose) and Day 2 | Baseline was defined as Day 1 Pre-dose. |
| Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 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 | 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 Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 up to Day 180 | — |
| Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | From Day 1 up to Day 180 | 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. |
| Number of Participants With Clinically Significant Physical Examination Findings | From Day 1 up to Day 60 | — |
| Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | From Day 1 up to Day 60 | — |
| Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | From Day 1 up to Day 60 | — |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | From Day 1 up to Day 60 | — |
| Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3 | Baseline (Day 1 pre-dose) and Day 3 | Baseline is defined as Day 1 pre-dose. |
| Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7 | Baseline (Day 1 pre-dose) and Day 7 | Baseline is defined as Day 1 pre-dose. |
| Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8 | Baseline (Day 1 pre-dose) and Day 8 | Baseline is defined as Day 1 pre-dose. |
| Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10 | Baseline (Day 1 pre-dose) and Day 10 | Baseline is defined as Day 1 pre-dose. |
| Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14 | Baseline (Day 1 pre-dose) and Day 14 | Baseline is defined as Day 1 pre-dose. |
Secondary
| Measure | Time frame |
|---|---|
| Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | 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 | 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 | 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 | 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 | 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 | 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 |
| Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | 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 |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 5 investigative sites in the United States from 23 January 2018 to 22 July 2019.
Pre-assignment details
Participants diagnosed with celiac disease (CD) were enrolled to receive TIMP-GLIA as a single dose escalation of 0.1 milligram per kilogram (mg/kg), 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 4.0 mg/kg, 8.0 mg/kg in Part A; and TIMP-GLIA as a two dose escalation of 2.0 mg/kg, 4.0 mg/kg, 8.0 mg/kg in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A, Cohort 1: 0.1 mg/kg TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1. | 2 |
| Part A, Cohort 2: 0.5 mg/kg TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1. | 2 |
| Part A, Cohort 3: 1.0 mg/kg TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1. | 3 |
| Part A, Cohort 4: 2.0 mg/kg TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1. | 3 |
| Part A, Cohort 5: 4.0 mg/kg TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1. | 3 |
| Part A, Cohort 6: 8.0 mg/kg TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1. | 4 |
| Part B, Cohort 1: 2.0 mg/kg TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8. | 2 |
| Part B, Cohort 2: 4.0 mg/kg TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8. | 2 |
| Part B, Cohort 3: 8.0 mg/kg TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8. | 2 |
| Total | 23 |
Baseline characteristics
| Characteristic | Part A, Cohort 1: 0.1 mg/kg | Total | Part B, Cohort 3: 8.0 mg/kg | Part B, Cohort 2: 4.0 mg/kg | Part B, Cohort 1: 2.0 mg/kg | Part A, Cohort 6: 8.0 mg/kg | Part A, Cohort 5: 4.0 mg/kg | Part A, Cohort 4: 2.0 mg/kg | Part A, Cohort 3: 1.0 mg/kg | Part A, Cohort 2: 0.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.5 years STANDARD_DEVIATION 27.58 | 40.3 years STANDARD_DEVIATION 13.69 | 32.5 years STANDARD_DEVIATION 2.12 | 53.5 years STANDARD_DEVIATION 7.78 | 42.5 years STANDARD_DEVIATION 13.44 | 27.5 years STANDARD_DEVIATION 4.65 | 48.3 years STANDARD_DEVIATION 14.19 | 38.0 years STANDARD_DEVIATION 4.58 | 39.3 years STANDARD_DEVIATION 15.57 | 53.5 years STANDARD_DEVIATION 20.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 22 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 22 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants |
| Region of Enrollment United States | 2 Participants | 23 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 18 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 2 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 1 / 2 | 2 / 2 | 3 / 3 | 3 / 3 | 2 / 3 | 3 / 4 | 1 / 2 | 1 / 2 | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 2 | 0 / 2 | 0 / 2 |
Outcome results
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 1 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 2 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 2 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 1 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 1 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 2 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels
Time frame: From Day 1 up to Day 60
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | 0 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | 0 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | 0 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | 0 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | 0 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | 0 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels | 0 Participants |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 0 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 0 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 0 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 0 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 0 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 0 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis | 0 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
Time frame: From Day 1 up to Day 60
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 0 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 0 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 0 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 0 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 0 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 0 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values | 0 Participants |
Primary
Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings
Time frame: From Day 1 up to Day 60
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | 0 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | 0 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | 0 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | 0 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | 0 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | 0 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings | 0 Participants |
Primary
Number of Participants With Clinically Significant Laboratory Abnormalities
Time frame: From Day 1 up to Day 60
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities | 1 Participants |
Primary
Number of Participants With Clinically Significant Physical Examination Findings
Time frame: From Day 1 up to Day 60
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Grade 3 or Higher TEAEs | 0 Participants |
| Part A, Cohort 1: 0.1 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Drug-related Adverse Events | 1 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Grade 3 or Higher TEAEs | 0 Participants |
| Part A, Cohort 2: 0.5 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Drug-related Adverse Events | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Grade 3 or Higher TEAEs | 1 Participants |
| Part A, Cohort 3: 1.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Drug-related Adverse Events | 2 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Grade 3 or Higher TEAEs | 0 Participants |
| Part A, Cohort 4: 2.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Drug-related Adverse Events | 2 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Grade 3 or Higher TEAEs | 0 Participants |
| Part A, Cohort 5: 4.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Drug-related Adverse Events | 2 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Drug-related Adverse Events | 3 Participants |
| Part A, Cohort 6: 8.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Grade 3 or Higher TEAEs | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Drug-related Adverse Events | 0 Participants |
| Part B, Cohort 1: 2.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Grade 3 or Higher TEAEs | 0 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Grade 3 or Higher TEAEs | 0 Participants |
| Part B, Cohort 2: 4.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Drug-related Adverse Events | 1 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Grade 3 or Higher TEAEs | 0 Participants |
| Part B, Cohort 3: 8.0 mg/kg | Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events | Drug-related Adverse Events | 1 Participants |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | 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 | 0 Participants |
| Part A, Cohort 2: 0.5 mg/kg | 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 | 0 Participants |
| Part A, Cohort 3: 1.0 mg/kg | 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 | 0 Participants |
| Part A, Cohort 4: 2.0 mg/kg | 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 | 0 Participants |
| Part A, Cohort 5: 4.0 mg/kg | 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 | 0 Participants |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10 | Baseline (Day 1 pre-dose) | 2.15 U/ml | Standard Deviation 0.495 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10 | Change at Day 10 | 1.85 U/ml | Standard Deviation 0.778 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10 | Baseline (Day 1 pre-dose) | 2.85 U/ml | Standard Deviation 0.778 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10 | Change at Day 10 | 1.00 U/ml | Standard Deviation 1.273 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10 | Baseline (Day 1 pre-dose) | 3.30 U/ml | Standard Deviation 0.99 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10 | Change at Day 10 | 1.25 U/ml | Standard Deviation 1.485 |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14 | Baseline (Day 1 pre-dose) | 2.15 U/ml | Standard Deviation 0.495 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14 | Change at Day 14 | 0.90 U/ml | Standard Deviation 0.141 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14 | Baseline (Day 1 pre-dose) | 2.85 U/ml | Standard Deviation 0.778 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14 | Change at Day 14 | 1.65 U/ml | Standard Deviation 0.495 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14 | Change at Day 14 | 1.30 U/ml | Standard Deviation 1.273 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14 | Baseline (Day 1 pre-dose) | 3.30 U/ml | Standard Deviation 0.99 |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3 | Baseline (Day 1 pre-dose) | 2.15 units per milliliter (U/ml) | Standard Deviation 0.495 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3 | Change at Day 3 | 1.20 units per milliliter (U/ml) | Standard Deviation 0 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3 | Baseline (Day 1 pre-dose) | 2.85 units per milliliter (U/ml) | Standard Deviation 0.778 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3 | Change at Day 3 | 0.60 units per milliliter (U/ml) | Standard Deviation 0.141 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3 | Baseline (Day 1 pre-dose) | 3.30 units per milliliter (U/ml) | Standard Deviation 0.99 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3 | Change at Day 3 | -0.35 units per milliliter (U/ml) | Standard Deviation 0.071 |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA. The safety analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38 | Baseline (Day 1 pre-dose) | 2.15 U/ml | Standard Deviation 0.495 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38 | Change at Day 38 | 0.30 U/ml | — |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38 | Baseline (Day 1 pre-dose) | 2.85 U/ml | Standard Deviation 0.778 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38 | Change at Day 38 | 1.50 U/ml | Standard Deviation 1.273 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38 | Baseline (Day 1 pre-dose) | 3.30 U/ml | Standard Deviation 0.99 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38 | Change at Day 38 | 1.00 U/ml | Standard Deviation 1.98 |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60 | Baseline (Day 1 pre-dose) | 2.15 U/ml | Standard Deviation 0.495 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60 | Change at Day 60 | 0.65 U/ml | Standard Deviation 0.354 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60 | Baseline (Day 1 pre-dose) | 2.85 U/ml | Standard Deviation 0.778 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60 | Change at Day 60 | 1.15 U/ml | Standard Deviation 1.061 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60 | Baseline (Day 1 pre-dose) | 3.30 U/ml | Standard Deviation 0.99 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60 | Change at Day 60 | 1.10 U/ml | Standard Deviation 1.838 |
Primary
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7
Baseline is defined as Day 1 pre-dose.
Time frame: Baseline (Day 1 pre-dose) and Day 7
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7 | Baseline (Day 1 pre-dose) | 2.15 U/ml | Standard Deviation 0.495 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7 | Change at Day 7 | 0.75 U/ml | Standard Deviation 0.071 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7 | Baseline (Day 1 pre-dose) | 2.85 U/ml | Standard Deviation 0.778 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7 | Change at Day 7 | 0.00 U/ml | Standard Deviation 0 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7 | Baseline (Day 1 pre-dose) | 3.30 U/ml | Standard Deviation 0.99 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7 | Change at Day 7 | 0.85 U/ml | Standard Deviation 1.344 |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA. The safety analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8 | Baseline (Day 1 pre-dose) | 2.15 U/ml | Standard Deviation 0.495 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8 | Change at Day 8 | 0.70 U/ml | Standard Deviation 0.141 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8 | Baseline (Day 1 pre-dose) | 2.85 U/ml | Standard Deviation 0.778 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8 | Change at Day 8 | 0.10 U/ml | — |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8 | Baseline (Day 1 pre-dose) | 3.30 U/ml | Standard Deviation 0.99 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8 | Change at Day 8 | 1.50 U/ml | Standard Deviation 1.838 |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): C3a level | 32.25 nanogram per milliliter (ng/mL) | Standard Deviation 23.264 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Change at 15 min post-dose on Day 1: C3a level | 45.40 nanogram per milliliter (ng/mL) | Standard Deviation 43.841 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): SC5B-9 level | 109.5 nanogram per milliliter (ng/mL) | Standard Deviation 17.68 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Change at 15 min post-dose on Day 1: SC5B-9 level | 59.0 nanogram per milliliter (ng/mL) | Standard Deviation 49.5 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Change at 15 min post-dose on Day 1: SC5B-9 level | 196.0 nanogram per milliliter (ng/mL) | Standard Deviation 193.75 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): C3a level | 16.15 nanogram per milliliter (ng/mL) | Standard Deviation 0.636 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): SC5B-9 level | 95.5 nanogram per milliliter (ng/mL) | Standard Deviation 33.23 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Change at 15 min post-dose on Day 1: C3a level | 134.90 nanogram per milliliter (ng/mL) | Standard Deviation 104.369 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Change at 15 min post-dose on Day 1: SC5B-9 level | 130.5 nanogram per milliliter (ng/mL) | Standard Deviation 33.23 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Change at 15 min post-dose on Day 1: C3a level | 46.25 nanogram per milliliter (ng/mL) | Standard Deviation 13.93 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): SC5B-9 level | 112.0 nanogram per milliliter (ng/mL) | Standard Deviation 33.94 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): C3a level | 18.65 nanogram per milliliter (ng/mL) | Standard Deviation 17.041 |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): C3a level | 32.25 ng/mL | Standard Deviation 23.264 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Change at 30 min post-dose on Day 1: C3a level | 87.50 ng/mL | Standard Deviation 56.569 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): SC5B-9 level | 109.5 ng/mL | Standard Deviation 17.68 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Change at 30 min post-dose on Day 1: SC5B-9 level | 179.0 ng/mL | Standard Deviation 2.83 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Change at 30 min post-dose on Day 1: SC5B-9 level | 307.0 ng/mL | Standard Deviation 41.01 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): C3a level | 16.15 ng/mL | Standard Deviation 0.636 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): SC5B-9 level | 95.5 ng/mL | Standard Deviation 33.23 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Change at 30 min post-dose on Day 1: C3a level | 144.00 ng/mL | Standard Deviation 11.455 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Change at 30 min post-dose on Day 1: SC5B-9 level | 293.0 ng/mL | Standard Deviation 185.26 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Change at 30 min post-dose on Day 1: C3a level | 65.65 ng/mL | Standard Deviation 34.719 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): SC5B-9 level | 112.0 ng/mL | Standard Deviation 33.94 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 | Baseline (Day 1 pre-dose): C3a level | 18.65 ng/mL | Standard Deviation 17.041 |
Primary
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
Population: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Baseline (Day 1 pre-dose): C3a level | 32.25 ng/mL | Standard Deviation 23.264 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Change at Day 2: C3a level | -6.55 ng/mL | Standard Deviation 12.092 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Baseline (Day 1 pre-dose): SC5B-9 level | 109.5 ng/mL | Standard Deviation 17.68 |
| Part A, Cohort 1: 0.1 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Change at Day 2: SC5B-9 level | 26.0 ng/mL | Standard Deviation 14.14 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Change at Day 2: SC5B-9 level | -12.5 ng/mL | Standard Deviation 36.06 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Baseline (Day 1 pre-dose): C3a level | 16.15 ng/mL | Standard Deviation 0.636 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Baseline (Day 1 pre-dose): SC5B-9 level | 95.5 ng/mL | Standard Deviation 33.23 |
| Part A, Cohort 2: 0.5 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Change at Day 2: C3a level | 0.90 ng/mL | Standard Deviation 0.99 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Change at Day 2: SC5B-9 level | 2.0 ng/mL | Standard Deviation 22.63 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Change at Day 2: C3a level | -6.70 ng/mL | Standard Deviation 20.789 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Baseline (Day 1 pre-dose): SC5B-9 level | 112.0 ng/mL | Standard Deviation 33.94 |
| Part A, Cohort 3: 1.0 mg/kg | Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 | Baseline (Day 1 pre-dose): C3a level | 18.65 ng/mL | Standard Deviation 17.041 |
Secondary
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
Population: The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 2: 0.5 mg/kg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA | Day 1 | 604 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 3.4 |
| Part A, Cohort 3: 1.0 mg/kg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA | Day 1 | 3100 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27 |
| Part A, Cohort 4: 2.0 mg/kg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA | Day 1 | 3170 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 22.8 |
| Part A, Cohort 5: 4.0 mg/kg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA | Day 1 | 8430 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 48.9 |
| Part A, Cohort 6: 8.0 mg/kg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA | Day 1 | NA hour*nanogram per milliliter (h*ng/mL) | — |
| Part B, Cohort 1: 2.0 mg/kg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA | Day 1 | 3220 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31.5 |
| Part B, Cohort 1: 2.0 mg/kg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA | Day 8 | NA hour*nanogram per milliliter (h*ng/mL) | — |
| Part B, Cohort 2: 4.0 mg/kg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA | Day 1 | 5080 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 9.2 |
| Part B, Cohort 2: 4.0 mg/kg | AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA | Day 8 | 3250 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 15.1 |
Secondary
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
Population: The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 1 | 119 h*ng/mL | Geometric Coefficient of Variation 210.7 |
| Part A, Cohort 2: 0.5 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 1 | 503 h*ng/mL | Geometric Coefficient of Variation 12.1 |
| Part A, Cohort 3: 1.0 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 1 | 1690 h*ng/mL | Geometric Coefficient of Variation 88.1 |
| Part A, Cohort 4: 2.0 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 1 | 2920 h*ng/mL | Geometric Coefficient of Variation 21.6 |
| Part A, Cohort 5: 4.0 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 1 | 2870 h*ng/mL | Geometric Coefficient of Variation 501.3 |
| Part A, Cohort 6: 8.0 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 1 | 932 h*ng/mL | Geometric Coefficient of Variation 65.2 |
| Part A, Cohort 6: 8.0 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 8 | NA h*ng/mL | — |
| Part B, Cohort 1: 2.0 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 8 | 1410 h*ng/mL | Geometric Coefficient of Variation 107.1 |
| Part B, Cohort 1: 2.0 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 1 | 2930 h*ng/mL | Geometric Coefficient of Variation 30.6 |
| Part B, Cohort 2: 4.0 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 1 | 4590 h*ng/mL | Geometric Coefficient of Variation 9.6 |
| Part B, Cohort 2: 4.0 mg/kg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA | Day 8 | 3050 h*ng/mL | Geometric Coefficient of Variation 14.7 |
Secondary
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
Population: The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 1 | 50.6 ng/mL | Geometric Coefficient of Variation 12.2 |
| Part A, Cohort 2: 0.5 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 1 | 63.9 ng/mL | Geometric Coefficient of Variation 29.2 |
| Part A, Cohort 3: 1.0 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 1 | 68.6 ng/mL | Geometric Coefficient of Variation 27.2 |
| Part A, Cohort 4: 2.0 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 1 | 55.8 ng/mL | Geometric Coefficient of Variation 30.2 |
| Part A, Cohort 5: 4.0 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 1 | 77.2 ng/mL | Geometric Coefficient of Variation 23.7 |
| Part A, Cohort 6: 8.0 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 1 | 97.9 ng/mL | Geometric Coefficient of Variation 85.1 |
| Part A, Cohort 6: 8.0 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 8 | NA ng/mL | — |
| Part B, Cohort 1: 2.0 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 8 | 133 ng/mL | Geometric Coefficient of Variation 137.7 |
| Part B, Cohort 1: 2.0 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 1 | 47.9 ng/mL | Geometric Coefficient of Variation 19 |
| Part B, Cohort 2: 4.0 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 1 | 111 ng/mL | Geometric Coefficient of Variation 5.7 |
| Part B, Cohort 2: 4.0 mg/kg | Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA | Day 8 | 54.4 ng/mL | Geometric Coefficient of Variation 19.5 |
Secondary
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
Population: The pharmacokinetic (PK) population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 1 | 91.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48.4 |
| Part A, Cohort 2: 0.5 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 1 | 220 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 3 |
| Part A, Cohort 3: 1.0 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 1 | 457 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17.6 |
| Part A, Cohort 4: 2.0 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 1 | 845 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23.6 |
| Part A, Cohort 6: 8.0 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 8 | NA nanogram per milliliter (ng/mL) | — |
| Part A, Cohort 6: 8.0 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 1 | 252 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 6.7 |
| Part B, Cohort 1: 2.0 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 1 | 529 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22.6 |
| Part B, Cohort 1: 2.0 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 8 | 408 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26.8 |
| Part B, Cohort 2: 4.0 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 8 | 735 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 11.7 |
| Part B, Cohort 2: 4.0 mg/kg | Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA | Day 1 | 938 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 2.9 |
Secondary
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
Population: The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 1 | NA hour |
| Part A, Cohort 2: 0.5 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 1 | 1.81 hour |
| Part A, Cohort 3: 1.0 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 1 | 4.38 hour |
| Part A, Cohort 4: 2.0 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 1 | 3.03 hour |
| Part A, Cohort 5: 4.0 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 1 | 4.36 hour |
| Part A, Cohort 6: 8.0 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 1 | NA hour |
| Part B, Cohort 1: 2.0 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 1 | 4.60 hour |
| Part B, Cohort 1: 2.0 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 8 | NA hour |
| Part B, Cohort 2: 4.0 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 1 | 3.03 hour |
| Part B, Cohort 2: 4.0 mg/kg | T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA | Day 8 | 2.51 hour |
Secondary
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
Population: The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 1 | 2.49 hour |
| Part A, Cohort 2: 0.5 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 1 | 4.00 hour |
| Part A, Cohort 3: 1.0 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 1 | 12.17 hour |
| Part A, Cohort 4: 2.0 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 1 | 12.00 hour |
| Part A, Cohort 5: 4.0 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 1 | 12.00 hour |
| Part A, Cohort 6: 8.0 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 1 | 7.99 hour |
| Part A, Cohort 6: 8.0 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 8 | NA hour |
| Part B, Cohort 1: 2.0 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 8 | 8.01 hour |
| Part B, Cohort 1: 2.0 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 1 | 18.10 hour |
| Part B, Cohort 2: 4.0 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 1 | 12.00 hour |
| Part B, Cohort 2: 4.0 mg/kg | Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA | Day 8 | 12.08 hour |
Secondary
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
Population: The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A, Cohort 1: 0.1 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 1 | 0.54 hour |
| Part A, Cohort 2: 0.5 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 1 | 0.50 hour |
| Part A, Cohort 3: 1.0 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 1 | 0.50 hour |
| Part A, Cohort 4: 2.0 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 1 | 0.50 hour |
| Part A, Cohort 6: 8.0 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 8 | NA hour |
| Part A, Cohort 6: 8.0 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 1 | 2.86 hour |
| Part B, Cohort 1: 2.0 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 1 | 3.21 hour |
| Part B, Cohort 1: 2.0 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 8 | 3.08 hour |
| Part B, Cohort 2: 4.0 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 8 | 2.90 hour |
| Part B, Cohort 2: 4.0 mg/kg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA | Day 1 | 2.94 hour |