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A multicenter, single-arm, open-label, phase III clinical study to investigate the efficacy and safety of GB-0706 in patients developing heparin resistance during cardiovascular surgery using a cardiopulmonary bypass

A multicenter, single-arm, open-label, phase III clinical study to investigate the efficacy and safety of GB-0706 in patients developing heparin resistance during cardiovascular surgery using a cardiopulmonary bypass

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The mean (+-) standard deviation (SD) age at the time of informed consent was 68.9 (+-) 7.06 years, with 12 male patients (40%). The mean (+-) SD for height was 158.58 (+-) 10.206 cm, and for weight was 55.74 (+-) 12.701 kg. At screening, the mean (+-) SD platelet count was 23.72 (+-) 4.904 x 10^4 /micro L, and the mean (+-) SD fibrinogen level was 342.8 (+-) 84.38 mg/dL. The mean (+-) SD antithrombin activity in the preoperative examination was 87.8 (+-) 10.35%.

This clinical trial had a target enrollment of 70 subjects to verify the primary endpoint. However, the trial was discontinued when 30 subjects had been treated with the investigational drug, at which point the efficacy rate of GB-0706 was 50%. The decision was made to terminate the trial because it was determined that there was a low probability of reaching the expected efficacy endpoint if the study were to continue (futility), and due to the possibility that it would not provide a beneficial treatment to the subjects. Efficacy analysis population: 30 cases (FAS), efficacy analysis population: 30 cases (PPS), safety analysis population: 30 cases

In this clinical trial, the incidence of adverse events was 73.3% (22 of 30 subjects), with a total of 47 events reported. The incidence of adverse drug reactions was 3.3% (1 of 30 subjects), with one event reported. No significant safety concerns were identified in this trial.

The efficacy rate, which was the primary endpoint, was 50% (95% CI: 31.3-68.7). This endpoint was defined as the proportion of subjects who achieved an Activated Clotting Time (ACT) of 480 seconds or longer (indicating an improved heparin resistance, HR) after the administration of the investigational drug (after the first dose or, if applicable, the second dose). The primary endpoint was not met, as the lower limit of the 95% confidence interval failed to exceed the pre-specified minimum efficacy rate of 50% for this trial. Regarding the secondary endpoint, which was the change in ACT from the time of supplemental heparin administration to after the investigational drug administration, a prolongation was observed following the administration of GB-0706. The mean (+-) standard deviation of this change was 28.1 (+-) 26.04 seconds (p < 0.001 by paired t-test).

The efficacy rate, which was the primary endpoint, was 50% (95% CI: 31.3-68.7). The primary endpoint was not met, as the lower limit of the 95% confidence interval failed to exceed the pre-specified minimum efficacy rate of 50% for this trial. No significant safety concerns were identified in this trial.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230269

Saiki Yoshikatsu

National University Corporation Tohoku University Tohoku University Hospital

1-1 Seiryocho, Aobaku, Sendai, Miyagi, Japan

c-development@jbpo.or.jp

Yata Hiroaki

Japan Blood Products Organization

15F Tamachi Station TowerN, 3-1-1 Shibaura, Minato-ku, Tokyo, Japan

+81-3-6435-6515

c-development@jbpo.or.jp

Complete

Aug. 01, 2023

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. 18 years old or older and 85 years or younger at the time when informed consent is obtained
2. Receiving elective cardiovascular surgery using a cardiopulmonary bypass
3. Platelet count of 178,000 / microliter or more at laboratory tests at screening
4. Fibrinogen count of 264 mg/dL or more at laboratory tests at screening
5. Meeting all the inclusion criteria 1 to 4 and found to have Heparin Resistance according to the definition of Heparin Resistance specified in this study

1. Having been administered a specified prohibited concomitant drug or prohibited concomitant therapy before administration of the study drug
2. Having congenital antithrombin III deficiency
3. Having a history of heparin-induced thrombocytopenia
4. Having a history of antiphospholipid syndrome
5. Receiving surgery other than cardiovascular surgery at the same time
6. Found to have a history of coagulation disorder (such as von Willebrand disease) for reasons such as a medical history of hemorrhagic disease or test history
7. Having congenital or acquired coagulation factor deficiency or abnormality

Both

Patients developing heparin resistance during cardiovascular surgery using a cardiopulmonary bypass

GB-0706 will be administered as the quantity of a single dose is 1,500 IU of antithrombin. If Heparin resistance does not improve after administration of study drug one dose, an additional dose, study drug dose will be administered.
(A maximum dose is 3,000 IU)

The percentage of subjects with ACT 480 seconds or over (improved Heparin resistance) after administration of the study drug (study drug dose (1), or, if the study drug is administered twice, study drug dose (2)).

The change in ACT from the additional dose of heparin to after administration of the study drug (study drug dose (1), or, if the study drug is administered twice, study drug dose (2))

July. 25, 2023

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