Phase 2 Study of Rivaroxaban Reversal by Ciraparantag as Measured by WBCT

Study Overview
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Brief Summary
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This study is a randomized, single-blind, placebo-controlled study to assess the efficacy and safety of ciraparantag administered to healthy volunteers anticoagulated with rivaroxaban measuring clotting times using Whole Blood Clotting Time (WBCT).

Detailed Description
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This is a randomized, single-blind, placebo-controlled assessment of the efficacy and safety of ciraparantag administered to healthy volunteers measuring clotting times using WBCT as determined by the manual testing method. All subjects will undergo screening up to 36 days prior to enrollment. All enrolled subjects are to receive a single dose of 20 mg rivaroxaban in the morning on Days 1-3. On Day 3 (3.75 hours post rivaroxaban), subjects who have a minimum increase in clotting time of 25% (as measured by WBCT) are randomized and will receive a single IV dose 4 hours after the rivaroxaban dose, followed by serial testing of manual WBCT. Subjects are enrolled sequentially in up to 4 ciraparantag dose cohorts. There will be a safety review after completion of treatment in one cohort and prior to initiation of treatment in the subsequent cohort.

Official Title
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Phase 2 Placebo-Controlled, Single-Site, Single-Blind Study of Rivaroxaban Reversal by Ciraparantag as Measured by WBCT

Conditions
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Healthy

Intervention / Treatment
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* Drug: Ciraparantag
* Drug: Placebo
* Drug: Rivaroxaban


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria: Adults age 50 to 75 years Laboratory tests (chemistry, hematology and coagulation assessments) and urinalysis performed during screening up to 36 days prior to administration of study treatment deemed not clinically significant by the principal investigator. No clinically significant findings on 12-lead electrocardiogram (ECG) performed during screening Body mass index (BMI) 18 to ≤ 32 kg/m2, inclusive Male subjects agree to use appropriate contraception in addition to their partner using an acceptable form of contraception, when engaging in sexual activity during the course of the study. Moreover, male subjects should not donate sperm or attempt to impregnate a partner during the course of the study and for a period of 12 weeks following discharge from the study. Female subjects must have a negative urine pregnancy test at screening AND: be surgically sterile OR postmenopausal for the last three months, OR in a monogamous relation with a male partner who has undergone a documented vasectomy a minimum of 6 months prior to study commencement. All females must agree to continue to use their method of birth control for the duration of the study and for a minimum of one complete menstrual cycle or 28 days following discharge from the study Subjects who have participated in a prior study of ciraparantag must have been discharged from the study a minimum of 1 month prior to the planned treatment. Subjects must understand and agree to comply with the requirements of the study and they must be willing to sign the informed consent form indicating voluntary consent to participate in the study prior to initiation of screening or study-related activities General Exclusion Criteria: History of major bleeding or clotting disorder Females with a history of dysfunctional uterine bleeding Smokers or use of tobacco and/or nicotine containing products within 3 months prior to dosing as determined by the subject's verbal history Pregnant or breast-feeding Males with a history of hormone therapy within 3 months prior to screening Taking any type of chronic medication (including vitamin, nutritional and herbal supplements) for more than 14 consecutive days within the 4 weeks prior to study entry (use of hormonal contraceptives is acceptable) Positive serologic test for human immunodeficiency virus (HIV), Hepatitis C virus antibody (HCV-Ab), or Hepatitis B surface antigen (HBsAg) Donation of blood or blood products within 56 days prior to screening Participation in any study with an investigational compound or device within 30 days prior to signing informed consent Active drug or alcohol dependence within the prior 12 months or any condition that, in the opinion of the Investigator, would interfere with adherence to study protocol

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>ciraparantag (60 mg) | Drug: Ciraparantag<br>* Ciraparantag (administered over 10 minutes)<br>* Other names: AMAG 977;Drug: Rivaroxaban<br>* Rivaroxaban 20 mg given once per day (QD) in the morning<br>|
| Experimental: Cohort 2<br>ciraparantag (120 mg) | Drug: Ciraparantag<br>* Ciraparantag (administered over 10 minutes)<br>* Other names: AMAG 977;Drug: Rivaroxaban<br>* Rivaroxaban 20 mg given once per day (QD) in the morning<br>|
| Experimental: Cohort 3<br>ciraparantag (180 mg) | Drug: Ciraparantag<br>* Ciraparantag (administered over 10 minutes)<br>* Other names: AMAG 977;Drug: Rivaroxaban<br>* Rivaroxaban 20 mg given once per day (QD) in the morning<br>|
| Experimental: Cohort 4<br>ciraparantag (30 mg) | Drug: Ciraparantag<br>* Ciraparantag (administered over 10 minutes)<br>* Other names: AMAG 977;Drug: Rivaroxaban<br>* Rivaroxaban 20 mg given once per day (QD) in the morning<br>|
| Placebo Comparator: Placebo<br>placebo (saline for injection) | Drug: Placebo<br>* Saline for injection<br>* Other names: PBO;Drug: Rivaroxaban<br>* Rivaroxaban 20 mg given once per day (QD) in the morning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of ciraparantag in the reversal of anticoagulation induced by rivaroxaban measured by WBCT | Efficacy of ciraparantag in the reversal of anticoagulation induced by rivaroxaban at steady state measured by WBCT. | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of rivaroxaban, ciraparantag and its major metabolite. | Pharmacokinetic parameters (including maximum concentration values and area under the curve) will be summarized for each treatment group. | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PER977, Ciraparantag, Whole Blood Clotting Time (WBCT), Rivaroxaban