10 Aptamers for Thrombotic Diseases
297
repeat doses of pegnivacogin achieved highly reproducible APTT levels with low
intrasubject variability and that repeat doses of anivamersen dose-dependently and
reproducibly reversed APTT values. This study also revealed that no residual effect
of anivamersen was observed when volunteers were administered with pegnivacogin.
RNA aptamer-oligonucleotide antidote pair was well tolerated and no major bleeding
or other serious side effects were observed [80].
In an open-label, multi-center, randomized, feasibility, and safety phase 2a study,
REG1 was compared with UFH during PCI, which was conducted in 26 stable CAD
patients enrolled in five hospitals. All patients underwent elective PCI and received
REG1 anticoagulation system combined with intravenous GP IIb/IIIa antagonist [81].
This phase 2a trial demonstrated that REG1 was applicable for titratable reversibility
in the setting of PCI. Both 50% and 100% anivamersen reversal strategies achieved
scheduled femoral sheath removal. There were two ischemic events in the REG1
group and one ischemic event in the UFH group, with one major bleeding event in
the UFH group. No serious events, episodes of stent thrombosis, or clot formation
in catheters were observed. This study confirms REG1 has a desired anticoagulant
effect when combined with antiplatelet therapy (aspirin and clopidogrel) during elective PCI in patients with stable CAD [81]. (NCT00715455) (https://www.clinicaltria
ls.gov.)
In a randomized partially blinded, multi-center, active-controlled, dose-ranging
phase 2b study (RADAR), the safety, efficacy, and pharmacodynamics of REG1
were assessed and compared with heparin in patients with non-ST-elevation ACS
undergoing PCI. The RADAR clinical trial was a further phase 2b investigation of
the efficacy of REG1 in 33 ACS patients during planned early cardiac catheterization.
RADAR revealed that an optimal dose of 1 mg/kg of pegnivacogin achieved > 99%
inhibition of FIX activity in patients with ACS and provided stable anticoagulation
during cardiac catheterization [82]. Consequently, to determine the optimal level of
reversal allowing safe sheath removal and the feasibility of using REG1 to prevent
ischaemic events, ACS patients undergoing PCI and non-ST-elevation ACS patients
with planned early cardiac catheterization via femoral access were randomized to
pegnivacogin with different doses of anivamersen for reversal or heparin. Bleeding,
ischaemic events, and adverse events were compared. The study also suggested that at
least 50% anivamersen reversal was required for safe femoral artery sheath removal
and that of 75 or 100% reversal may result in less bleeding compared with UFH
[69]. RADAR study indicated that REG1 is a safe anticoagulant strategy in ACS
patients undergoing PCI, CAD, and venous thromboembolism, especially for the
early management of patients with ACS. (NCT00932100) (https://www.clinicaltria
ls.gov) [78].
However, enrollment was stopped after 640 subjects were enrolled because of
three serious allergic reactions in the REG1 arm. Importantly, major bleeding was
significantly reduced in the REG1 100% reversal arm (7.3%) as compared with the
heparin arm (10.1%). This study did not show a difference in ischemic events of
different arms, but suggested REG1 may be an appealing anticoagulant agent in
ACS patients undergoing cardiac catheterization [69].
297
repeat doses of pegnivacogin achieved highly reproducible APTT levels with low
intrasubject variability and that repeat doses of anivamersen dose-dependently and
reproducibly reversed APTT values. This study also revealed that no residual effect
of anivamersen was observed when volunteers were administered with pegnivacogin.
RNA aptamer-oligonucleotide antidote pair was well tolerated and no major bleeding
or other serious side effects were observed [80].
In an open-label, multi-center, randomized, feasibility, and safety phase 2a study,
REG1 was compared with UFH during PCI, which was conducted in 26 stable CAD
patients enrolled in five hospitals. All patients underwent elective PCI and received
REG1 anticoagulation system combined with intravenous GP IIb/IIIa antagonist [81].
This phase 2a trial demonstrated that REG1 was applicable for titratable reversibility
in the setting of PCI. Both 50% and 100% anivamersen reversal strategies achieved
scheduled femoral sheath removal. There were two ischemic events in the REG1
group and one ischemic event in the UFH group, with one major bleeding event in
the UFH group. No serious events, episodes of stent thrombosis, or clot formation
in catheters were observed. This study confirms REG1 has a desired anticoagulant
effect when combined with antiplatelet therapy (aspirin and clopidogrel) during elective PCI in patients with stable CAD [81]. (NCT00715455) (https://www.clinicaltria
ls.gov.)
In a randomized partially blinded, multi-center, active-controlled, dose-ranging
phase 2b study (RADAR), the safety, efficacy, and pharmacodynamics of REG1
were assessed and compared with heparin in patients with non-ST-elevation ACS
undergoing PCI. The RADAR clinical trial was a further phase 2b investigation of
the efficacy of REG1 in 33 ACS patients during planned early cardiac catheterization.
RADAR revealed that an optimal dose of 1 mg/kg of pegnivacogin achieved > 99%
inhibition of FIX activity in patients with ACS and provided stable anticoagulation
during cardiac catheterization [82]. Consequently, to determine the optimal level of
reversal allowing safe sheath removal and the feasibility of using REG1 to prevent
ischaemic events, ACS patients undergoing PCI and non-ST-elevation ACS patients
with planned early cardiac catheterization via femoral access were randomized to
pegnivacogin with different doses of anivamersen for reversal or heparin. Bleeding,
ischaemic events, and adverse events were compared. The study also suggested that at
least 50% anivamersen reversal was required for safe femoral artery sheath removal
and that of 75 or 100% reversal may result in less bleeding compared with UFH
[69]. RADAR study indicated that REG1 is a safe anticoagulant strategy in ACS
patients undergoing PCI, CAD, and venous thromboembolism, especially for the
early management of patients with ACS. (NCT00932100) (https://www.clinicaltria
ls.gov) [78].
However, enrollment was stopped after 640 subjects were enrolled because of
three serious allergic reactions in the REG1 arm. Importantly, major bleeding was
significantly reduced in the REG1 100% reversal arm (7.3%) as compared with the
heparin arm (10.1%). This study did not show a difference in ischemic events of
different arms, but suggested REG1 may be an appealing anticoagulant agent in
ACS patients undergoing cardiac catheterization [69].