Ulcerative Colitis
Conditions
Brief summary
The primary objectives of this study are as follows: * To assess the safety and tolerability of escalating single and multiple doses of GS-5745 (andecaliximab) in participants with moderate to severe ulcerative colitis (UC) as assessed by adverse events (AEs) and laboratory abnormalities * To assess the pharmacokinetics (PK) of GS-5745 (andecaliximab) in participants with moderate to severe UC.
Detailed description
The study will test the safety of the drug. Participants will be given different concentrations of the drug in Cohorts, starting from a lower dose to a higher dose. Single-Dose Treatment: A thorough assessment of safety and tolerability will be performed before escalating to the next higher dose. For example, the first 2 participants will be dosed in a staggered fashion 24 hours apart. Provided that there are no significant safety signals up to 24 hours post-dose for the first 2 participants, the remaining 4 participants will be dosed. A thorough assessment of safety and tolerability (through Day 14 post-dose) will be performed by the safety review committee before escalating to the next higher dose. Participants enrolled in a SAD cohort will be eligible to participate in a MAD or adaptive MAD cohort if eligibility criteria are met. Multiple-Dose Treatment: This design follows the same set-up as the Single-Dose Treatment. Dosing will not commence in the first MAD cohort until safety data from the second dose level SAD cohort has been reviewed through Day 15. Successive MAD cohorts will only be dosed after safety data from the previous, lower dose MAD cohort through Day 43 and the next higher dose SAD cohort through Day 15, have been reviewed by the safety review committee. An additional Adaptive MAD cohort will explore a subcutaneous dosing of andecaliximab 150 mg prefilled syringe once a week for 5 weeks.
Interventions
DRUGAndecaliximab
Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection
Placebo to match andecaliximab administered by IV infusion
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or Female, 18 to 65 years of age * Negative pregnancy test at screening * Documented diagnosis of UC with a minimum disease extent of 15 centimeters (cm) from the anal verge * Mayo Score of at least 3 for the SAD cohort and Mayo Score of at least 6 for the MAD cohorts * Hepatic panel (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total bilirubin, direct bilirubin, alkaline phosphatase, lactate dehydrogenase \[LDH\] ≤ 2 times the upper limit of the normal range \[ULN\]) * Serum creatinine ≤ 1.5 times the ULN * Hemoglobin ≥ 10 grams per deciliter (g/dL) (both males and females) * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1,500 milli meters \[mm\]\^3) * Platelets ≥ 100 x 10\^9/L. Key
Exclusion criteria
* Pregnant or lactating females * Exhibit severe UC/ clinically significant active infection * Current use of oral corticosteroids at a dose equivalent to \> 20 mg/day of prednisone * Any dose adjustment in oral corticosteroids or oral immunosuppressants (6-MP, Azathioprine), or oral 5-aminosalicylate (5-ASA) compounds within 30 days of Baseline * Use of rectal formulations of 5-ASA compounds or corticosteroids within 2 weeks prior to randomization * Crohn's disease or indeterminate colitis * History of colectomy, partial colectomy, or dysplasia on biopsy * Stool sample positive for Clostridium difficile (C. difficile) toxin, E. coli, Salmonella, Shigella, Campylobacter or Yersinia * Treatment with Infliximab, Adalimumab, Natalizumab, Golimumab, Vedolizumab or Certolizumab within 8 weeks of randomization * Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) that, in the opinion of the Investigator, would make the individual unsuitable for the study or would prevent compliance with the study protocol. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | SAD Cohorts: First dose date (Day 1) plus 30 days, MAD/Adaptive MAD Cohort: First dose date up to last dose date (Maximum: Day 29) plus 30 days | TEAEs are any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. |
| Pharmacokinetic (PK) Parameter: Cmax (SAD) | Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43 | Cmax is defined as the maximum concentration of drug. |
| PK Parameter: Cmax (MAD) | MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Days 1 and 29, Predose on Days 8 and 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Days 1, and 29, Predose on Days 8 and 36 | Cmax is defined as the maximum concentration of drug over the dosing interval. Data for Day 1 was based on the data collected from Day 1 through Day 8. Data for Day 29 was based on the data collected from Day 29 through Day 36. |
| PK Parameter: Ctau (MAD) | MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Day 29; Predose on Day 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Day 29; Predose on Day 36 | Ctau is defined as the observed drug concentration at the end of the dosing interval. |
| PK Parameter: AUCinf (SAD) | Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43 | AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. |
| PK Parameter: AUCtau (MAD) | MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Days 1 and 29; Predose on Days 8 and 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Days 1, and 29; Predose on Days 8 and 36 | AUCtau is defined as the area under the plasma concentration versus time curve over the dosing interval. Data for Day 1 was based on the data collected from Day 1 through Day 8. Data for Day 29 was based on the data collected from Day 29 through Day 36. |
| PK Parameter: AUClast (SAD) | Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43 | AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last observable concentration. |
Countries
Belgium, Canada, Hungary, Moldova, Netherlands, Romania, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, and Europe. The first participant was screened on 28 March 2013. The last study visit occurred on 06 February 2015.
Pre-assignment details
124 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Andecaliximab 0.3 mg/kg IV (SAD) Participants received a single IV infusion of andecaliximab 0.3 mg/kg on Day 1. | 5 |
| Andecaliximab 1.0 mg/kg IV (SAD) Participants received a single IV infusion of andecaliximab 1.0 mg/kg on Day 1. | 5 |
| Andecaliximab 2.5 mg/kg IV (SAD) Participants received a single IV infusion of andecaliximab 2.5 mg/kg on Day 1. | 5 |
| Andecaliximab 5.0 mg/kg IV (SAD) Participants received a single IV infusion of andecaliximab 5.0 mg/kg on Day 1. | 5 |
| Placebo Pooled (SAD) Participants received a single IV infusion of placebo on Day 1. | 4 |
| Andecaliximab 0.3 mg/kg IV (MAD) Participants received 3 single IV infusions of andecaliximab 0.3 mg/kg on Days 1, 15, and 29. | 8 |
| Andecaliximab 1.0 mg/kg IV (MAD) Participants received 3 single IV infusions of andecaliximab 1.0 mg/kg on Days 1, 15, and 29. | 8 |
| Andecaliximab 2.5 mg/kg IV (MAD) Participants received 3 single IV infusions of andecaliximab 2.5 mg/kg on Days 1, 15, and 29. | 8 |
| Andecaliximab 5.0 mg/kg IV (MAD) Participants received 3 single IV infusions of andecaliximab 5.0 mg/kg on Days 1, 15, and 29. | 8 |
| Andecaliximab 150 mg SC (Adaptive MAD) Participants received 5 single SC doses of andecaliximab 150 mg on Days 1, 8, 15, 22, and 29. | 10 |
| Placebo Pooled (MAD) Participants received 3 single IV infusions of placebo on Days 1, 15, and 29. | 8 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 |
| Overall Study | Investigator's Discretion | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrew Consent | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Andecaliximab 2.5 mg/kg IV (SAD) | Andecaliximab 0.3 mg/kg IV (SAD) | Andecaliximab 1.0 mg/kg IV (SAD) | Andecaliximab 5.0 mg/kg IV (SAD) | Placebo Pooled (SAD) | Andecaliximab 0.3 mg/kg IV (MAD) | Andecaliximab 1.0 mg/kg IV (MAD) | Andecaliximab 2.5 mg/kg IV (MAD) | Andecaliximab 5.0 mg/kg IV (MAD) | Andecaliximab 150 mg SC (Adaptive MAD) | Placebo Pooled (MAD) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 15.4 | 42 years STANDARD_DEVIATION 11.3 | 37 years STANDARD_DEVIATION 11.3 | 42 years STANDARD_DEVIATION 12.9 | 41 years STANDARD_DEVIATION 15.1 | 42 years STANDARD_DEVIATION 13.9 | 39 years STANDARD_DEVIATION 11.7 | 38 years STANDARD_DEVIATION 13.7 | 50 years STANDARD_DEVIATION 9.8 | 48 years STANDARD_DEVIATION 8.8 | 44 years STANDARD_DEVIATION 15.8 | 43 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 4 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 10 Participants | 8 Participants | 74 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 | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race 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 | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 8 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 5 Participants | 2 Participants | 3 Participants | 5 Participants | 3 Participants | 7 Participants | 7 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 64 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 5 Participants | 3 Participants | 5 Participants | 2 Participants | 6 Participants | 3 Participants | 38 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 5 Participants | 3 Participants | 6 Participants | 4 Participants | 5 Participants | 36 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 20 | 0 / 4 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 32 | 0 / 10 | 0 / 42 | 0 / 8 |
| other Total, other adverse events | 0 / 5 | 0 / 5 | 1 / 5 | 3 / 5 | 4 / 20 | 1 / 4 | 2 / 8 | 6 / 8 | 5 / 8 | 5 / 8 | 18 / 32 | 5 / 10 | 23 / 42 | 5 / 8 |
| serious Total, serious adverse events | 0 / 5 | 1 / 5 | 0 / 5 | 0 / 5 | 1 / 20 | 0 / 4 | 1 / 8 | 1 / 8 | 0 / 8 | 0 / 8 | 2 / 32 | 0 / 10 | 2 / 42 | 1 / 8 |
Outcome results
Primary
Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD)
TEAEs are any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug.
Time frame: SAD Cohorts: First dose date (Day 1) plus 30 days, MAD/Adaptive MAD Cohort: First dose date up to last dose date (Maximum: Day 29) plus 30 days
Population: The Safety Analysis Set included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Andecaliximab 0.3 mg/kg IV (SAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 0.0 percentage of participants |
| Andecaliximab 1.0 mg/kg IV (SAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 20.0 percentage of participants |
| Andecaliximab 2.5 mg/kg IV (SAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 20.0 percentage of participants |
| Andecaliximab 5.0 mg/kg IV (SAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 60.0 percentage of participants |
| Andecaliximab IV Combined (SAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 25.0 percentage of participants |
| Placebo Pooled (SAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 25.0 percentage of participants |
| Andecaliximab 0.3 mg/kg IV (MAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 25.0 percentage of participants |
| Andecaliximab 1.0 mg/kg IV (MAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 75.0 percentage of participants |
| Andecaliximab 2.5 mg/kg IV (MAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 62.5 percentage of participants |
| Andecaliximab 5.0 mg/kg IV (MAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 62.5 percentage of participants |
| Andecaliximab IV Combined (MAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 56.3 percentage of participants |
| Andecaliximab 150 mg SC (Adaptive MAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 50.0 percentage of participants |
| Andecaliximab IV+SC Combined (MAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 54.8 percentage of participants |
| Placebo Pooled (MAD) | Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD) | 62.5 percentage of participants |
Primary
Pharmacokinetic (PK) Parameter: Cmax (SAD)
Cmax is defined as the maximum concentration of drug.
Time frame: Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43
Population: Participants in the PK Analysis Set (who received at least 1 dose of study drug and had at least 1 non-missing post dose concentration value for the corresponding analyte in plasma) for the SAD cohorts were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab 0.3 mg/kg IV (SAD) | Pharmacokinetic (PK) Parameter: Cmax (SAD) | 9.4 micrograms per milliliter (μg/mL) | Standard Deviation 3.28 |
| Andecaliximab 1.0 mg/kg IV (SAD) | Pharmacokinetic (PK) Parameter: Cmax (SAD) | 32.7 micrograms per milliliter (μg/mL) | Standard Deviation 11.08 |
| Andecaliximab 2.5 mg/kg IV (SAD) | Pharmacokinetic (PK) Parameter: Cmax (SAD) | 77.8 micrograms per milliliter (μg/mL) | Standard Deviation 20.67 |
| Andecaliximab 5.0 mg/kg IV (SAD) | Pharmacokinetic (PK) Parameter: Cmax (SAD) | 210.0 micrograms per milliliter (μg/mL) | Standard Deviation 102.6 |
Primary
PK Parameter: AUCinf (SAD)
AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.
Time frame: Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43
Population: Participants in the PK Analysis Set for SAD cohorts were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab 0.3 mg/kg IV (SAD) | PK Parameter: AUCinf (SAD) | 9.4 day*micrograms per milliliter(day*μg/mL) | Standard Deviation 4.44 |
| Andecaliximab 1.0 mg/kg IV (SAD) | PK Parameter: AUCinf (SAD) | 66.6 day*micrograms per milliliter(day*μg/mL) | Standard Deviation 22.85 |
| Andecaliximab 2.5 mg/kg IV (SAD) | PK Parameter: AUCinf (SAD) | 240.8 day*micrograms per milliliter(day*μg/mL) | Standard Deviation 23.69 |
| Andecaliximab 5.0 mg/kg IV (SAD) | PK Parameter: AUCinf (SAD) | 817.3 day*micrograms per milliliter(day*μg/mL) | Standard Deviation 405.97 |
Primary
PK Parameter: AUClast (SAD)
AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last observable concentration.
Time frame: Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43
Population: Participants in the PK Analysis Set for SAD cohorts were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab 0.3 mg/kg IV (SAD) | PK Parameter: AUClast (SAD) | 7.7 day*μg/mL | Standard Deviation 2.54 |
| Andecaliximab 1.0 mg/kg IV (SAD) | PK Parameter: AUClast (SAD) | 57.2 day*μg/mL | Standard Deviation 26.96 |
| Andecaliximab 2.5 mg/kg IV (SAD) | PK Parameter: AUClast (SAD) | 212.4 day*μg/mL | Standard Deviation 38.79 |
| Andecaliximab 5.0 mg/kg IV (SAD) | PK Parameter: AUClast (SAD) | 750.2 day*μg/mL | Standard Deviation 412.42 |
Primary
PK Parameter: AUCtau (MAD)
AUCtau is defined as the area under the plasma concentration versus time curve over the dosing interval. Data for Day 1 was based on the data collected from Day 1 through Day 8. Data for Day 29 was based on the data collected from Day 29 through Day 36.
Time frame: MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Days 1 and 29; Predose on Days 8 and 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Days 1, and 29; Predose on Days 8 and 36
Population: Participants in the PK Analysis Set for MAD and Adaptive MAD cohorts with available data were analyzed. Concentrations fell below the limit of quantitation early in the dosing interval for some participants in some of the cohorts. Therefore, AUCtau couldn't be adequately estimated and was not included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab 0.3 mg/kg IV (SAD) | PK Parameter: AUCtau (MAD) | NA day*μg/mL | — |
| Andecaliximab 1.0 mg/kg IV (SAD) | PK Parameter: AUCtau (MAD) | 79.2 day*μg/mL | Standard Deviation 53.98 |
| Andecaliximab 2.5 mg/kg IV (SAD) | PK Parameter: AUCtau (MAD) | 251.8 day*μg/mL | Standard Deviation 88.15 |
| Andecaliximab 5.0 mg/kg IV (SAD) | PK Parameter: AUCtau (MAD) | 784.8 day*μg/mL | Standard Deviation 262.5 |
| Andecaliximab IV Combined (SAD) | PK Parameter: AUCtau (MAD) | 166.8 day*μg/mL | Standard Deviation 164.53 |
Primary
PK Parameter: Cmax (MAD)
Cmax is defined as the maximum concentration of drug over the dosing interval. Data for Day 1 was based on the data collected from Day 1 through Day 8. Data for Day 29 was based on the data collected from Day 29 through Day 36.
Time frame: MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Days 1 and 29, Predose on Days 8 and 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Days 1, and 29, Predose on Days 8 and 36
Population: Participants in the PK Analysis Set for MAD cohort (with available data) and Adaptive MAD cohort were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Andecaliximab 0.3 mg/kg IV (SAD) | PK Parameter: Cmax (MAD) | Day 1 | 9.0 μg/mL | Standard Deviation 3.23 |
| Andecaliximab 0.3 mg/kg IV (SAD) | PK Parameter: Cmax (MAD) | Day 29 | 10.3 μg/mL | Standard Deviation 5.06 |
| Andecaliximab 1.0 mg/kg IV (SAD) | PK Parameter: Cmax (MAD) | Day 1 | 33.7 μg/mL | Standard Deviation 26.43 |
| Andecaliximab 1.0 mg/kg IV (SAD) | PK Parameter: Cmax (MAD) | Day 29 | 29.0 μg/mL | Standard Deviation 10.89 |
| Andecaliximab 2.5 mg/kg IV (SAD) | PK Parameter: Cmax (MAD) | Day 1 | 57.1 μg/mL | Standard Deviation 13.66 |
| Andecaliximab 2.5 mg/kg IV (SAD) | PK Parameter: Cmax (MAD) | Day 29 | 66.6 μg/mL | Standard Deviation 15.02 |
| Andecaliximab 5.0 mg/kg IV (SAD) | PK Parameter: Cmax (MAD) | Day 29 | 120.8 μg/mL | Standard Deviation 21.15 |
| Andecaliximab 5.0 mg/kg IV (SAD) | PK Parameter: Cmax (MAD) | Day 1 | 95.3 μg/mL | Standard Deviation 28.93 |
| Andecaliximab IV Combined (SAD) | PK Parameter: Cmax (MAD) | Day 1 | NA μg/mL | — |
| Andecaliximab IV Combined (SAD) | PK Parameter: Cmax (MAD) | Day 29 | 33.5 μg/mL | Standard Deviation 42.47 |
Primary
PK Parameter: Ctau (MAD)
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time frame: MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Day 29; Predose on Day 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Day 29; Predose on Day 36
Population: Participants in the PK Analysis Set for MAD and Adaptive MAD cohorts were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab 0.3 mg/kg IV (SAD) | PK Parameter: Ctau (MAD) | NA μg/mL | — |
| Andecaliximab 1.0 mg/kg IV (SAD) | PK Parameter: Ctau (MAD) | NA μg/mL | — |
| Andecaliximab 2.5 mg/kg IV (SAD) | PK Parameter: Ctau (MAD) | 0.8 μg/mL | Standard Deviation 2.36 |
| Andecaliximab 5.0 mg/kg IV (SAD) | PK Parameter: Ctau (MAD) | 27.2 μg/mL | Standard Deviation 13.99 |
| Andecaliximab IV Combined (SAD) | PK Parameter: Ctau (MAD) | 16.0 μg/mL | Standard Deviation 15.99 |