Clinical trial NCT04593784: Study of Ciraparantag for Reversal of Anticoagulation Induced by Edoxaban, Apixaban or Rivaroxaban in Healthy Adults
Official title: A Phase 2 Randomized, Double-blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Ciraparantag for Reversal of Anticoagulation in Healthy Adults
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Healthy
Keywords: ciraparantag
PER977
Apixaban
Rivaroxaban
Whole Blood Clotting Time (WBCT)
Coagulometer
AMAG 977
Edoxaban
Lead sponsor: AMAG Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Ciraparantag Holdings GmbH
First posted: 2020-10-20
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study will be conducted in 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.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Provide written informed consent.
2. 18 to 75 years of age.
3. Be in generally good health
4. BMI 18 to 32 kg/m2, inclusive, at Screening.
5. 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 1.
6. If male, be surgically sterile, or agree to use appropriate contraception.
7. Have suitable venous access for multiple venipunctures.

Exclusion Criteria:

1. Have any of the following findings at Screening:

   1. Hemoglobin or hematocrit value outside the normal range
   2. Platelet count outside the normal range
   3. PT or aPTT outside the normal range
   4. Plasma fibrinogen outside the normal range
   5. Serum triglycerides or total cholesterol outside the normal range
   6. Serum creatinine \>1.5 mg/dL (133 μmol/L) or known renal disease
   7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2 x the upper limit of normal, or known liver disease
   8. Total bilirubin outside the normal range
   9. Positive viral screen for hepatitis B virus, hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
   10. Positive pregnancy test (females)
   11. Positive drug, tobacco or alcohol screen
   12. Any clinically significant findings on 12-lead ECG or urinalysis
2. Have a personal or family history of clotting disorder or hematologic abnormality.
3. Have a history of unexplained syncope.
4. Have a history within 6 months prior to Screening of major bleeding, trauma, surgical procedure of any type, or vaginal delivery
5. Have a history within 6 months prior to Screening of peptic ulcer or gastrointestinal bleeding.
6. Have received any blood product or anticoagulant within 3 months prior to Screening.
7. Have donated blood or blood products within 3 months prior to Screening
8. Have a history of minor bleeding episodes within 1 month prior to Screening, or a long-standing history of such bleeding.
9. If female, have a history of excessive or dysfunctional uterine bleeding (unless the subject had a subsequent hysterectomy).
10. Have used any tobacco or nicotine-containing products within 3 months prior to Screening.
11. Have used any systemic prescription or non-prescription drugs within 14 days prior to Day 1 (except for permitted contraceptives).
12. If female, be pregnant, breastfeeding, or planning to become pregnant during the study.
13. Have received ciraparantag in any prior clinical study.
14. Have received another investigational drug within 5 half-lives or 30 days, whichever is longer, prior to Day 1.
15. Known allergy to edoxaban, apixaban or rivaroxaban.
16. 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.

Primary outcomes:
measure: 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.
timeFrame: 6 Hours
Secondary outcomes:
measure: 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.
timeFrame: 6 Hours
measure: 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.
timeFrame: 6 Hours
measure: 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.
timeFrame: 6 Hours
measure: 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.
timeFrame: 6 Hours
measure: 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.
timeFrame: 6 Hours
measure: 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.
timeFrame: 6 Hours
measure: 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.
timeFrame: 6 Hours
measure: 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.
timeFrame: 6 Hours
measure: Correlation between WBCT measured with Perosphere Technologies' POC Coagulometer and with a manual testing method
timeFrame: 24 Hours
Other outcomes:
Locations:
city: South Miami
country: United States
facility: Qps-Mra, Llc.
state: Florida
city: Secaucus
country: United States
facility: Frontage Clinical Services
state: New Jersey
city: San Antonio
country: United States
facility: ICON Early Phase Services, LLC
state: Texas
Study officials:
References: