TAK-755 (previously known as SHP655) is a medicine used to treat sickle cell disease (SCD). The main aim of the study is to measure the safety and tolerability of TAK-755 in SCD participants. Study participants will receive TAK-755 or placebo on Day 1. Their SCD will be treated by their doctor according to their doctor's usual clinical practice. During the study, participants will be asked to follow-up on 13 days following SHP655 or placebo administration for safety assessment. Maximum duration of participation is expected to be about 2 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
19
University of Alabama at Birmingham
Birmingham, Alabama, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product (IP) or medicinal product. TEAEs were defined as AEs that started or worsened in severity on or after the infusion of IP. A serious TEAEs was any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which resulted in death, was life-threatening, required inpatient hospitalization, prolongation of hospitalization, was an important medical event. TEAEs included both serious and non-serious AEs.
Time frame: From date of signing informed consent up to end of study visit (Day 28)
Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755
Measurement of Anti-ADAMTS13 antibodies can be used to assess whether the body's immune system has been stimulated to react to TAK-755. Binding Anti-ADAMTS13 antibodies measure antibodies that are able to bind to ADAMTS13, whether or not the antibodies have an effect on how well ADAMTS13 works. An inhibitory Anti-ADAMTS13 antibody is antibody that both binds to ADAMTS13 and able to affect how well ADAMTS13 works. Binding and Inhibitory anti-ADAMTS13 antibodies were categorized as pre-existing, treatment-induced, and treatment-boosted. Pre-existing: anti-ADAMTS13 antibodies were detected in the baseline sample prior to infusion with TAK-755. Treatment-induced: no anti-ADAMTS13 antibodies were detected in baseline sample but were detected in any sample drawn after TAK-755 infusion. Treatment-boosted: anti-ADAMTS13 antibodies were pre-existing and were detected at any time after TAK-755 infusion at titers that were at least 4 steps higher than the titers detected before TAK-755 infusion.
Time frame: From date of signing informed consent up to end of study visit (Day 28)
Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
IR was defined as the ratio of maximum increase in plasma ADAMTS13 antigen or activity level to TAK-755 dose per body weight. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. Here "IU/mL/IU/kg" refers to "International units per milliliter per international units per kilogram".
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University of Colorado Sickle Cell Treatment and Research Center
Aurora, Colorado, United States
Sickle Cell Center
Denver, Colorado, United States
University of Illinois
Chicago, Illinois, United States
Ochsner Health System
New Orleans, Louisiana, United States
Johns Hopkins University School Of Medicine
Baltimore, Maryland, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
East Carolina University
Greenville, North Carolina, United States
...and 4 more locations
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Cmax was a measure of the maximum amount of drug in the plasma after the dose was given. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Tmax was a measure of the time to reach the maximum concentration in the plasma after the drug dose. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
t1/2 was the time required for a given drug concentration in the plasma to decrease by 50%. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
The MRT is the average time that the study product stays in the body (or plasma). The MRT0-Inf is defined as the average time from zero (pre-dose) extrapolated to infinite time (MRT0-inf). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Mean Residence Time From Zero to 72 Hours Post-dose (MRT0-72) of ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
The MRT is the average time that the study product stays in the body (or plasma) and The MRT0-72 is defined as the average time from zero (predose) to 72 hours post-dose (MRT0-72). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
AUC0-Last was an area under the concentration-time curve from zero (pre-dose) to time of last quantifiable concentration. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
AUC0-72 was an area under the concentration-time curve from zero (predose) to 72 hours post-dose (AUC0-72). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
AUC0-inf was area under the concentration-time curve from zero (pre-dose) extrapolated to infinite time. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC\[0-infinity\]). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by MRT(0-inf)\*CL. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints
Von Willebrand factor (vWF or VWF) is a protein that is one of several components of the coagulation system that work together to stop bleeding within the body. VWF:Ag measures the level of von Willebrand factor protein in the blood. The change from baseline in VWF:Ag concentration was measured at different time points. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints
Von Willebrand factor (vWF or VWF) is a protein that is one of several components of the coagulation system that work together, to stop bleeding within the body. VWF:RCo assay is a test that measures the activity of the VWF in a plasma sample in terms of how well it is able to clump platelets together in the presence of the antibiotic ristocetin. Change from baseline in vWF:RCo concentration was measured at different timepoints. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Platelet Count at Specified Timepoints
Blood samples were collected to analyze platelet count. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Thechange from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints
The plasma free hemoglobin test measures the level of hemoglobin in the plasma (that is, not contained within the red blood cells). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints
Change from baseline in plasma thrombospondin levels over time was reported. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 288, and 648 hours post-dose