Healthy
Conditions
Keywords
ciraparantag, PER977, Apixaban, Rivaroxaban, Whole Blood Clotting Time (WBCT), Coagulometer, AMAG 977, Edoxaban
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.
Interventions
DRUGCiraparantag
Ciraparantag: 180 mg, intravenous
DRUGPlacebo
Placebo: 0.9% sodium chloride, intravenous
DEVICEPoint-of-Care Coagulometer (investigational device)
Perosphere Technologies' Point of Care (POC) Coagulometer Device will be used to measure whole blood clotting time.
Sponsors
AMAG Pharmaceuticals, Inc.
Ciraparantag Holdings GmbH
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Achieving WBCT ≤120% of Baseline | 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). |
Countries
United States
Contacts
STUDY_DIRECTORAdvisor
Apollo Investment Management
Participant flow
Recruitment details
Screening occurred between Oct 2021 and Aug 2023 at 3 phase 1 clinics. Subjects were enrolled into the cohorts listed below (i.e., no participants were enrolled in Cohort 2, Apixaban 10mg).
Pre-assignment details
41 subjects were enrolled; 40 subjects were assigned to a cohort (1 subject discontinued due to cohort being full). Of the 40 subjects assigned to a cohort and dosed with anticoagulant, 37 subjects were randomized and 3 subjects were not randomized and discontinued the study early, prior to treatment with ciraparantag/placebo, due to not meeting study WBCT threshold for sufficient anticoagulation.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 45.4 Years STANDARD_DEVIATION 14.3 |
| Baseline Whole Blood Clotting Time (WBCT) as measured by PoC Coagulometer | 235.2 seconds STANDARD_DEVIATION 37.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 12 | 0 / 4 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 7 / 12 | 3 / 12 | 0 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 12 | 0 / 4 |
Outcome results
None listed