A Phase 2 Randomized, Double-blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Ciraparantag for Reversal of Anticoagulation in Healthy Adults
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 6
- 主要终点
- The number of subjects achieving WBCT ≤120% of baseline within 1 hour after administration of ciraparantag or placebo and sustained after 1 hour through at least 6 hours after ciraparantag/placebo dosing.
研究概览
简要总结
A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of ciraparantag for reversal of anticoagulation induced by different anticoagulant drugs in generally healthy adults as measured primarily by an automated coagulometer device.
详细描述
This is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of ciraparantag for reversal of anticoagulation induced by different anticoagulant drugs (edoxaban, apixaban or rivaroxaban) in generally healthy adults. Throughout the study, coagulation status will be determined by whole blood clotting time (WBCT), which will be measured primarily by the Perosphere Technologies' PoC Coagulometer and at selected timepoints using a manual testing method.
The study will be conducted in three separate cohorts; each cohort will evaluate the reversal of a different anticoagulant drug. Within each cohort, an initial group of subjects (Group 1) will be enrolled for evaluation of a target dose of ciraparantag. Depending on the efficacy and safety results from Group 1, a second group (Group 2) may be enrolled to evaluate a different dose of ciraparantag for that cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Anticoagulant drugs will be administered in an open-label manner. Ciraparantag or placebo (PBO) will be administered in a double-blind manner. Subjects and all study site personnel except the study pharmacist will be blinded to individual subject treatment assignment (ciraparantag or PBO). The Sponsor will be unblinded to individual treatment assignments.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provide written informed consent.
- •18 to 75 years of age.
- •Be in generally good health
- •BMI 18 to 32 kg/m2, inclusive, at Screening.
- •If female, be surgically sterile or post-menopausal or if of child-bearing potential, using an acceptable method of contraception (other than a combination estrogen/progestin hormonal contraceptive) for at least 1 month prior to Day
- •If male, be surgically sterile, or agree to use appropriate contraception.
- •Have suitable venous access for multiple venipunctures.
排除标准
- •Have any of the following findings at Screening:
- •Hemoglobin or hematocrit value outside the normal range
- •Platelet count outside the normal range
- •PT or aPTT outside the normal range
- •Plasma fibrinogen outside the normal range
- •Serum triglycerides or total cholesterol outside the normal range
- •Serum creatinine >1.5 mg/dL (133 μmol/L) or known renal disease
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 x the upper limit of normal, or known liver disease
- •Total bilirubin outside the normal range
- •Positive viral screen for hepatitis B virus, hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
- •Positive pregnancy test (females)
- •Positive drug, tobacco or alcohol screen
- •Any clinically significant findings on 12-lead ECG or urinalysis
- •Have a personal or family history of clotting disorder or hematologic abnormality.
- •Have a history of unexplained syncope.
- •Have a history within 6 months prior to Screening of major bleeding, trauma, surgical procedure of any type, or vaginal delivery
- •Have a history within 6 months prior to Screening of peptic ulcer or gastrointestinal bleeding.
- •Have received any blood product or anticoagulant within 3 months prior to Screening.
- •Have donated blood or blood products within 3 months prior to Screening
- •Have a history of minor bleeding episodes within 1 month prior to Screening, or a long-standing history of such bleeding.
- •If female, have a history of excessive or dysfunctional uterine bleeding (unless the subject had a subsequent hysterectomy).
- •Have used any tobacco or nicotine-containing products within 3 months prior to Screening.
- •Have used any systemic prescription or non-prescription drugs within 14 days prior to Day 1 (except for permitted contraceptives).
- •If female, be pregnant, breastfeeding, or planning to become pregnant during the study.
- •Have received ciraparantag in any prior clinical study.
- •Have received another investigational drug within 5 half-lives or 30 days, whichever is longer, prior to Day
- •Known allergy to edoxaban, apixaban or rivaroxaban.
- •Have any other condition that, in the opinion of the Investigator, would interfere with a subject's ability to adhere to the protocol, interfere with assessment of the investigational product, or compromise the safety of the subject or the quality of the data.
研究组 & 干预措施
Cohort 2
Subjects receive 10 mg apixaban orally every 12 hours on Days 1 to 3, with a final dose in the morning on Day 4. On Day 4, approximately 4 hours after administering apixaban, study drug (ciraparantag or placebo) will be intravenously administered.
干预措施: Point-of-Care Coagulometer (investigational device) (Device)
Cohort 3
Subjects receive 20 mg rivaroxaban orally once daily in the morning on Days 1 to 4. On Day 4, approximately 4 hours after administering rivaroxaban, study drug (ciraparantag or placebo) will be intravenously administered.
干预措施: Ciraparantag (Drug)
Cohort 3
Subjects receive 20 mg rivaroxaban orally once daily in the morning on Days 1 to 4. On Day 4, approximately 4 hours after administering rivaroxaban, study drug (ciraparantag or placebo) will be intravenously administered.
干预措施: Placebo (Drug)
Cohort 2
Subjects receive 10 mg apixaban orally every 12 hours on Days 1 to 3, with a final dose in the morning on Day 4. On Day 4, approximately 4 hours after administering apixaban, study drug (ciraparantag or placebo) will be intravenously administered.
干预措施: Ciraparantag (Drug)
Cohort 2
Subjects receive 10 mg apixaban orally every 12 hours on Days 1 to 3, with a final dose in the morning on Day 4. On Day 4, approximately 4 hours after administering apixaban, study drug (ciraparantag or placebo) will be intravenously administered.
干预措施: Placebo (Drug)
Cohort 1
Subjects receive 60 mg edoxaban orally once daily in the morning on Days 1 to 4. On Day 4, approximately 3 hours after administering edoxaban, study drug (ciraparantag or placebo) will be intravenously administered.
干预措施: Placebo (Drug)
Cohort 1
Subjects receive 60 mg edoxaban orally once daily in the morning on Days 1 to 4. On Day 4, approximately 3 hours after administering edoxaban, study drug (ciraparantag or placebo) will be intravenously administered.
干预措施: Point-of-Care Coagulometer (investigational device) (Device)
Cohort 3
Subjects receive 20 mg rivaroxaban orally once daily in the morning on Days 1 to 4. On Day 4, approximately 4 hours after administering rivaroxaban, study drug (ciraparantag or placebo) will be intravenously administered.
干预措施: Point-of-Care Coagulometer (investigational device) (Device)
Cohort 1
Subjects receive 60 mg edoxaban orally once daily in the morning on Days 1 to 4. On Day 4, approximately 3 hours after administering edoxaban, study drug (ciraparantag or placebo) will be intravenously administered.
干预措施: Ciraparantag (Drug)
结局指标
主要结局
The number of subjects achieving WBCT ≤120% of baseline within 1 hour after administration of ciraparantag or placebo and sustained after 1 hour through at least 6 hours after ciraparantag/placebo dosing.
时间窗: 6 Hours
Subjects Achieving WBCT ≤120% of Baseline
时间窗: Within 1 hour and sustained through 6 hours
The primary efficacy endpoint is achieving a WBCT (measured by PoC coagulometer) ≤ 120% of baseline within 1 hour after administration of ciraparantag/PBO, which is subsequently sustained after 1 hour through at least 6 hours after ciraparantag/PBO dosing (Responder).
次要结局
- The number of subjects achieving WBCT ≤115% of baseline within 1 hour after administration of ciraparantag or placebo and sustained after 1 hour through at least 6 hours after ciraparantag/placebo dosing.(6 Hours)
- The number of subjects achieving WBCT ≤120% of baseline within 15 minutes after administration of ciraparantag or placebo and sustained after 15 minutes through at least 6 hours after ciraparantag/placebo dosing.(6 Hours)
- The number of subjects achieving WBCT ≤110% of baseline within 15 minutes after administration of ciraparantag or placebo and sustained after 15 minutes through at least 6 hours after ciraparantag/placebo dosing.(6 Hours)
- Correlation between WBCT measured with Perosphere Technologies' POC Coagulometer and with a manual testing method(24 Hours)
- The number of subjects achieving WBCT ≤110% of baseline within 1 hour after administration of ciraparantag or placebo and sustained after 1 hour through at least 6 hours after ciraparantag/placebo dosing.(6 Hours)
- The number of subjects achieving WBCT ≤120% of baseline within 30 minutes after administration of ciraparantag or placebo and sustained after 30 minutes through at least 6 hours after ciraparantag/placebo dosing.(6 Hours)
- The number of subjects achieving WBCT ≤115% of baseline within 30 minutes after administration of ciraparantag or placebo and sustained after 30 minutes through at least 6 hours after ciraparantag/placebo dosing.(6 Hours)
- The number of subjects achieving WBCT ≤110% of baseline within 30 minutes after administration of ciraparantag or placebo and sustained after 30 minutes through at least 6 hours after ciraparantag/placebo dosing.(6 Hours)
- The number of subjects achieving WBCT ≤115% of baseline within 15 minutes after administration of ciraparantag or placebo and sustained after 15 minutes through at least 6 hours after ciraparantag/placebo dosing.(6 Hours)