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Phase 2B Study to Evaluate the Efficacy of PB2452 in Reversal of Ticagrelor in Subjects Aged 50-80 Years Old

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04122170
Recruitment Status : Completed
First Posted : October 10, 2019
Last Update Posted : October 8, 2021
Sponsor:
Information provided by (Responsible Party):
PhaseBio Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE October 4, 2019
First Posted Date  ICMJE October 10, 2019
Last Update Posted Date October 8, 2021
Actual Study Start Date  ICMJE October 14, 2019
Actual Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2021)
Reversal effect of intravenous infusion of PB2452 compared to baseline - Minimum % inhibition of PRU (VerifyNow) [ Time Frame: Four hours after the start of infusion (compared against pre-dose sample) ]
Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
Reversal effect of intravenous infusion of PB2452 compared to baseline - Minimum % inhibition of PRU (Verify Now) [ Time Frame: Four hours after the start of infusion (compared against pre-dose sample) ]
Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2021)
  • Safety - Incidence and severity of AEs [ Time Frame: 83 days - Starting up to 45 days prior to dosing ]
  • Safety - Incidence and severity of adverse events based on physical examination [ Time Frame: 83 days - Starting up to 45 days prior to dosing and collected pre-dose and Days 3, 7, and 35±3 ]
  • Safety - Incidence of Clinical Laboratory Testing Abnormalities [ Time Frame: 83 days - Starting up to 45 days prior to dosing, pre-dose and Day 2, 7 and 35±3 ]
  • Safety - Changes in Systolic Blood Pressure [ Time Frame: 83 days - Starting up to 45 days prior to dosing and collected pre-dose and Days 1, 2, 3, 7, and 35±3 ]
  • Safety - Changes in Diastolic Blood Pressure [ Time Frame: 83 days - Starting up to 45 days prior to dosing and collected pre-dose and Days 1, 2, 3, 7, and 35±3 ]
  • Safety - Changes in Oral Body Temperature [ Time Frame: 83 days - Starting up to 45 days prior to dosing and collected pre-dose and Days 1, 2, 3, 7, and 35±3 ]
  • Safety - Changes in Respiratory Rate [ Time Frame: 83 days - Starting up to 45 days prior to dosing and collected pre-dose and Days 1, 2, 3, 7, and 35±3 ]
  • Safety - Changes in Heart Rate [ Time Frame: 83 days - Starting up to 45 days prior to dosing and collected pre-dose and Days 1, 2, 3, 7, and 35±3 ]
  • Safety - Incidence of clinically significant findings as measured by 12-Lead ECG [ Time Frame: 83 days - Starting up to 45 days prior to dosing and collected pre-dose and Days 1, 2, 7, and 35±3 ]
  • Safety - Incidence of positive testing for Anti-Drug Antibodies [ Time Frame: 41 days - Starting 3 days prior to dosing and collected post-dose at Day 1, 7 and Day 35±3. May be extended in the event that result does not return to baseline in time allotted. ]
  • Cmax (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion (exact sample times may be adjusted) ]
    Maximum concentration
  • AUC (0-t) (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration (AUC0-t)
  • Tmax (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Time to maximum concentration
  • AUC0-24 (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24 hours after the start of infusion ]
    Area under the plasma concentration versus time curve 0-24 hours
  • AUC0-48 (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Area under the plasma concentration versus time curve 0-48 hours
  • AUC0-tau (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Area under the plasma concentration versus time curve from time zero to the time of the end of the dosing period
  • AUC0-inf (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Area under the plasma concentration versus time curve at time 0 extrapolated to infinity
  • t½ (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Terminal elimination half-life
  • CL (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Clearance
  • Vd (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Volume of distribution
  • Cmax (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Maximum concentration
  • AUC0-last (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, and 12 hours after the start of infusion ]
    Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration
  • Tmax (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Time to maximum concentration
  • AUC(0-24) (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, and 24 hours after the start of infusion ]
    Area under the plasma concentration versus time curve 0-24 hours
  • AUC(0-48) (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Area under the plasma concentration versus time curve 0-48 hours
  • AUC0-tau (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Area under the plasma concentration versus time curve from time zero to the time of the end of the dosing period
  • AUC0-inf (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Area under the plasma concentration versus time curve at time 0 extrapolated to infinity
  • t½ (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35±3 days after the start of infusion ]
    Terminal elimination half-life
  • Ae24 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the PB2452 infusion. ]
    Total amount of drug excreted in urine at 24 hours
  • Ae48 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the PB2452 infusion ]
    Total amount of drug excreted in urine at 48 hours
  • Aet1-t2 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the PB2452 infusion ]
    Total amount of drug excreted in urine from time t1 to t2 hours
  • Fe24 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the PB2452 infusion and 5th ticagrelor dose. ]
    Fraction excreted in urine from 1 to 24 hours
  • Fe48 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the PB2452 infusion and 5th ticagrelor dose ]
    Fraction excreted in urine from 1 to 48 hours
  • CLr (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the PB2452 infusion and 5th ticagrelor dose ]
    Renal clearance
  • Reversal effects of intravenous infusion of PB2452 compared to baseline - Minimum % inhibition of PRI (VASP) [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 compared to baseline - PRU (Verify Now) AUC [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects to ≥ 180 PRU [ Time Frame: Before dosing and 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects to ≥ 60% of reversal in PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects to ≥ 80% of reversal in PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects to ≥ 100% of reversal in PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 60% of reversal by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 80% of reversal by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 100% of reversal by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Duration of 80% response rate by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Duration of 100% response rate by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - PRI AUC [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects with ≥ 60% PRI response rate within 4 hours [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects with ≥ 80% PRI response rate within 4 hours [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects with ≥ 100% PRI response rate within 4 hours [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 60% of reversal by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 80% of reversal by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 100% of reversal by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Duration of 80% response rate by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Duration of 100% response rate by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % Reversal of PRU within 4 hours [ Time Frame: Before dosing and 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % Reversal of PRI within 4 hours [ Time Frame: Before dosing and 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
  • Safety - Incidence and severity of AEs [ Time Frame: 83 days - Starting up to 45 days prior to dosing ]
  • Safety - Incidence and severity of adverse events based on physical examination [ Time Frame: 83 days - Starting up to 45 days prior to dosing and collected pre-dose and Days 3, 7, and 35 ]
  • Safety - Incidence of Clinical Laboratory Testing Abnormalities [ Time Frame: 83 days - Starting day of dosing ]
  • Safety - Changes in Systolic Blood Pressure [ Time Frame: 83 days - Starting up to 45 days prior to dosing ]
  • Safety - Changes in Diastolic Blood Pressure [ Time Frame: 83 days - Starting up to 45 days prior to dosing ]
  • Safety - Changes in Oral Body Temperature [ Time Frame: 83 days - Starting up to 45 days prior to dosing ]
  • Safety - Changes in Respiratory Rate [ Time Frame: 83 days - Starting up to 45 days prior to dosing ]
  • Safety - Changes in Heart Rate [ Time Frame: 83 days - Starting up to 45 days prior to dosing ]
  • Safety - Incidence of clinically significant findings as measured by 12-Lead ECG [ Time Frame: 83 days - Starting up to 45 days prior to dosing ]
  • Safety - Incidence of positive testing for Anti-Drug Antibodies [ Time Frame: 41 days - Starting 3 days prior to dosing and collected post-dose at Day 1, 7 and Day 35. May be extended in the event that result does not return to baseline in time allotted. ]
  • Cmax (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Maximum concentration
  • AUC (0-t) (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Area under the plasma concentration versus time curve from 0 to the time of the last quantifiable concentration (AUC0-t)
  • Tmax (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Time to maximum concentration
  • AUC0-24 (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24 hours after the start of infusion ]
    Area under the plasma concentration versus time curve 0-24 hours
  • AUC0-48 (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Area under the plasma concentration versus time curve 0-48 hours
  • AUC0-tau (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Area under the plasma concentration versus time curve from time zero to the time of the end of the dosing period
  • AUC0-inf (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Area under the plasma concentration versus time curve at time 0 extrapolated to infinity
  • t½ (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Terminal elimination half-life
  • CL (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Clearance
  • Vd (PB2452) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Volume of distribution
  • Cmax (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Maximum concentration
  • AUC0-last (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, and 12 hours after the start of infusion ]
    Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration
  • Tmax (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Time to maximum concentration
  • AUC(0-24) (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, and 24 hours after the start of infusion ]
    Area under the plasma concentration versus time curve 0-24 hours
  • AUC(0-48) (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Area under the plasma concentration versus time curve 0-48 hours
  • AUC0-tau (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Area under the plasma concentration versus time curve from time zero to the time of the end of the dosing period
  • AUC0-inf (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Area under the plasma concentration versus time curve at time 0 extrapolated to infinity
  • t½ (Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36, 48 hours, 7 and 35 days after the start of infusion ]
    Terminal elimination half-life
  • Ae24 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the PB2452 infusion. ]
    Total amount of drug excreted in urine at 24 hours
  • Ae48 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the PB2452 infusion ]
    Total amount of drug excreted in urine at 48 hours
  • Aet1-t2 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the PB2452 infusion ]
    Total amount of drug excreted in urine from time t1 to t2 hours
  • Fe24 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the PB2452 infusion and 5th ticagrelor dose. ]
    Fraction excreted in urine from 1 to 24 hours
  • Fe48 (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the PB2452 infusion and 5th ticagrelor dose ]
    Fraction excreted in urine from 1 to 48 hours
  • CLr (Urine - Ticagrelor and Ticagrelor Active Metabolite (TAM)) [ Time Frame: Before dosing and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the PB2452 infusion and 5th ticagrelor dose ]
    Renal clearance
  • Reversal effects of intravenous infusion of PB2452 compared to baseline - Minimum % inhibition of PRI (VASP) [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 compared to baseline - PRU (Verify Now) AUC [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects to ≥ 180 PRU [ Time Frame: Before dosing and 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects to ≥ 60% of reversal in PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects to ≥ 80% of reversal in PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects to ≥ 100% of reversal in PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 60% of reversal by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 80% of reversal by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 100% of reversal by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Duration of 80% response rate by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Duration of 100% response rate by PRU [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - PRI AUC [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects with ≥ 60% PRI response rate within 4 hours [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects with ≥ 80% PRI response rate within 4 hours [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % of subjects with ≥ 100% PRI response rate within 4 hours [ Time Frame: Before dosing and at 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 60% of reversal by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 80% of reversal by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Time to ≥ 100% of reversal by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Duration of 80% response rate by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - Duration of 100% response rate by PRI [ Time Frame: Before dosing and at 5, 10 and 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
  • Reversal effects of intravenous infusion of PB2452 - % Reversal of PRU within 4 hours [ Time Frame: Before dosing and 4 hours after the start of infusion ]
    Reversal of anti-platelet effects of ticagrelor with intravenous infusion of PB2452 or placebo
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2B Study to Evaluate the Efficacy of PB2452 in Reversal of Ticagrelor in Subjects Aged 50-80 Years Old
Official Title  ICMJE A Phase 2B, Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy of PB2452 in Reversing Ticagrelor in Subjects Aged 50 to 80 Years Old
Brief Summary

This phase 2B study is a multi-center, randomized, double-blind, placebo-controlled study. The study is designed to evaluate the efficacy of PB2452 in reversing the anti-platelet effects of ticagrelor as part of a dual antiplatelet regimen and to evaluate the safety and tolerability of PB2452 in subjects aged 50-80 years old.

Approximately 200 subjects between 50-80 years old will be enrolled in the US or other countries at the discretion of the Sponsor across 5-15 sites. The subjects will be randomized at a ratio of 3:1 receiving either the PB2452 investigational study drug or placebo. Hence, a total of approximately 150 subjects will be receiving PB2452 and approximately 50 subjects will be receiving placebo.

Detailed Description

The study will consist of a Screening period, a Check-in day, an on-site Randomization/Treatment day, a 2-day on-site Follow-up period (Days 2 through 3), a Follow-up visit (Day 7), and a Final Follow-up visit (Day 35±3). If needed and at the discretion of the Investigator, a subject may remain in the study facility beyond the scheduled Day 3 discharge to accommodate Day 7 and Day 35±3 follow-up visits. Seven days prior to enrollment, subjects will be administered ASA 81 mg orally once daily (QD) until the final dose on Day 1. Beginning in the morning on Day -2, a single dose of oral ticagrelor 180 mg will be given, followed by oral ticagrelor 90 mg every 12 hours for 4 additional doses through to Day 1 (2 hours before study drug is initiated; this will be 5 total doses of ticagrelor).

On Day 1, subjects who meet all the inclusion criteria and none of the exclusion criteria will be randomized with 3:1 allocation ratio (active:placebo), to receive an IV dose of PB2452 or placebo 2 hours following the 5th ticagrelor dose. Subjects may be discharged from the clinical site on Day 3 and will return for a Follow-up visit on Day 7, if already discharged, and on Day 35 (±3 days). A subject may remain in the study facility beyond the scheduled Day 3 discharge to accommodate Day 7 and Day 35±3 follow-up visits.

If a subject is taking a moderate or strong CYP3A inhibitor, a 36 g alternative regimen of PB2452 will be administered consisting of 12 g infused over 10 minutes followed by a 12 g loading dose infused over 6 hours, then a maintenance dose of 12 g infused over the next 18 hours immediately following completion of the loading period for a total infusion time of approximately 24 hours.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: Ticagrelor Oral Tablet - Pre-Treatment
    Ticagrelor 90 mg oral tablet; administered as 180 mg (2 × 90 mg tablet) loading dose plus 90 mg every 12 hours for 4 additional doses.
  • Drug: Aspirin (ASA) Oral Tablet - Pre-Treatment
    Aspirin 81 mg oral tablet; administered daily between Day -7 to the morning before receiving study medication on Day 1, for a total of 8 tablets only.
  • Drug: PB2452 Infusion

    PB2452 18 g Intravenous Infusion over a 16 hour duration

    In subjects with potential drug interaction from concomitant use of moderate or strong CYP3A inhibitors with ticagrelor, the active treatment period may be 24 hours and 10 min if receiving the 36 g infusion.

  • Drug: Placebo (0.9% Sodium chloride) infusion
    0.9% Sodium chloride Intravenous Infusion over a 16 hour duration
Study Arms  ICMJE
  • Active Comparator: PB2452
    PB2452 18 g Intravenous Infusion over a 16 hour duration.
    Interventions:
    • Drug: Ticagrelor Oral Tablet - Pre-Treatment
    • Drug: Aspirin (ASA) Oral Tablet - Pre-Treatment
    • Drug: PB2452 Infusion
  • Placebo Comparator: Placebo
    Placebo (0.9% Sodium chloride) intravenous Infusion over a 16 hour duration.
    Interventions:
    • Drug: Ticagrelor Oral Tablet - Pre-Treatment
    • Drug: Aspirin (ASA) Oral Tablet - Pre-Treatment
    • Drug: Placebo (0.9% Sodium chloride) infusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 1, 2021)
203
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2019)
200
Actual Study Completion Date  ICMJE September 1, 2021
Actual Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • The subject provides written or verbal informed consent (in-person or remotely) and agrees to comply with all protocol requirements throughout study participation.
  • The subject is male or female between ≥50 and ≤80 years of age.
  • The subject has a body mass index between 18 and 35 kg/m2 and a weight of ≥ 50 kg but ≤ 120 kg, inclusive, at screening.
  • The subject is considered by the Investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12 lead ECG results, and physical examination findings at screening and Check-in. Subjects with chronic, stable, and well-controlled medical conditions, are eligible provided they meet all other inclusion/exclusion criteria.
  • The subject has specific inclusionary laboratory values at screening and check-in: white blood cell (WBC) count, platelet count, haemoglobin level, thyroid-stimulating hormone (TSH) level, and prothrombin time (PT) and partial thromboplastin time (PTT) levels within the normal range.
  • Subjects taking medications for well-controlled medical conditions must have been on a stable dose for at least 30 days prior to screening visit.
  • Subjects entering the study must be willing to start and/or document an 81 mg daily dose of aspirin on Day -7 and must document daily dosing until the final dose is administered on the morning of Day 1. Subjects already taking daily aspirin must suspend aspirin dosing after Day 1 until discharge from the clinical facility.
  • Female subjects of childbearing potential must not be pregnant, lactating, or planning to become pregnant for 3 months after the last dose of study drug. Female subjects of childbearing potential must use two effective methods of birth control from screening and before study drug administration through to the end of the study.

Exclusion Criteria:

  • In the opinion of the Investigator there are concern(s) regarding the inability of the subject to comply with study procedures and/or follow up, or, if the subject is not suitable for entry into the study.
  • History of any acute or chronic medical disorder expected to decrease the life expectancy of the subject to an extent where the subject's study participation is affected.
  • Any clinically significant acute illness, medical/surgical procedure, or trauma within 4 weeks of the administration of study drug or any planned surgical procedure that will occur during the study.
  • Any clinically significant abnormal findings in physical examination, vital signs, laboratory assessments, and ECG parameters identified during screening or check-in.
  • Any specific contraindication to ticagrelor as described in the ticagrelor prescribing information.
  • Receiving chronic treatment with nonsteroidal anti-inflammatory drugs [including aspirin (>100 mg daily), anticoagulants, or other antiplatelet agents that cannot be discontinued 14 days prior to screening including clopidogrel, prasugrel, ticlopidine, dipyridamole, or cilostazol].
  • First positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at screening.
  • Has received another investigational drug within 30 days of the administration of study drug in this study or within 5 half-lives of the experimental medication, whichever is longer.
  • History of severe or ongoing allergy/hypersensitivity to any biologic therapeutic agent.
  • Involvement with any PhaseBio or study site employee or their close relatives (e.g., spouse, parents, siblings, or children whether biological or legally adopted).
  • Previously received PB2452 or had been randomized to receive study drug in an earlier cohort for this study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04122170
Other Study ID Numbers  ICMJE PB2452-PT-CL-0003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PhaseBio Pharmaceuticals Inc.
Study Sponsor  ICMJE PhaseBio Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PhaseBio Pharmaceuticals Inc.
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP