Phase 2 N=134 Randomized Double-blind Treatment

Study to Assess the Safety, Pharmacokinetics/Dynamics of DS-1040b in Subjects With Acute Submassive Pulmonary Embolism

Pulmonary Embolism · Thrombotic Disease

Bottom Line

View on ClinicalTrials.gov: NCT02923115 ↗

Enrolled (actual)

134

Serious AEs

11.2%

Results posted

Jul 2020

Primary outcome: Primary: Number of Participants Experiencing Adjudicated Clinically Relevant Bleeding Events Following Intravenous Infusion of DS-1040b or Placebo in Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism — 4; 3; 3; 4 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: DS-1040b (Drug); Placebo (Drug); Enoxaparin (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Daiichi Sankyo
Primary completion: Aug 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants Experiencing Adjudicated Clinically Relevant Bleeding Events Following Intravenous Infusion of DS-1040b or Placebo in Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism	4; 3; 3; 4; 1; 10	—
SECONDARY Mean Percent Change From Baseline in Total Thrombus Volume at 12-72 Hours Post Start of Infusion of DS-1040b Compared to Placebo When Added to Standard of Care Anticoagulation Therapy in Participants With Acute Submassive Pulmonary Embolism	-23.78; -38.67; -33.50; -37.36; -32.33; -31.35	—
SECONDARY Participants Achieving Reductions in Total Thrombus Volume at 12-72 Hours Post Infusion of DS-1040b Compared to Placebo When Added to Standard of Care Anticoagulation Therapy in Participants With Acute Submassive Pulmonary Embolism	2; 0; 1; 0; 1; 3	—
SECONDARY Pharmacokinetic (PK) Parameter Maximum Concentration (CMax) Following Intravenous Infusion of DS-1040b in Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism	970.09; 421.73; 608.84; 1006.41; 526.12	—
SECONDARY Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve (0 to Last) Following Intravenous Infusion of DS-1040b In Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism	5532.92; 7819.53; 13403.15; 17147.27; 8014.73	—
SECONDARY Pharmacokinetic Parameter Terminal Half-life Following Intravenous Infusion of DS-1040b Combined With Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism	22.81; 28.44; 29.06; 36.39; 30.06	—

Summary

This is a Phase 1b, double-blind (participants and Investigators), placebo-controlled, randomized, single-ascending dose, multi-center study to assess the safety, efficacy, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040b in participants with acute submassive pulmonary embolism.

Eligibility Criteria

Inclusion Criteria

Male or female subjects, age 18 to 75 years admitted to hospital with a clinical diagnosis of acute pulmonary embolism (PE) categorized as low risk or intermediate-risk or submassive PE and for whom catheter-based therapy is not planned;
Subjects must have a computed tomography angiography (CTA) scan confirming the PE diagnosis and with at least one measurable index lesion in a segmental or larger pulmonary artery prior to randomization;
Subjects should be in otherwise satisfactory health in the opinion of the Investigator;
Subjects must be able to provide written informed consent.

Exclusion Criteria

Subjects with acute PE categorized as high-risk or massive, or who are hemodynamically unstable, evidenced by a heart rate > 120 /min and a systolic blood pressure (SBP) of 40 mmHg since presentation;
Subjects for whom use of a thrombolytic, either systemic or via catheter, is planned;
Subjects with PE lesions only in the sub-segmental or smaller arteries;
Subjects receiving any vitamin K antagonists (VKAs) prior to randomization or receiving more than 36 hours treatment with low molecular weight (LMW) Heparin in therapeutic doses prior to randomization;
Subjects who had a prior intracranial hemorrhage, known arteriovenous malformation or aneurysm, head trauma, or evidence of active bleeding;
Subjects who within 48 hours of randomization have used an anti-Factor IIa agent such as dabigatran or an anti-FXa agent such as rivaroxaban, apixaban, or edoxaban;
Subjects who within 21 days prior to randomization have had gastrointestinal or genitourinary bleeding;
Subjects who within 14 days prior to randomization have had major surgery or a lumbar puncture (or epidural steroid injection);
Subjects with diagnosed active liver disease or with elevation of liver enzymes/bilirubin.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02923115). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.