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

NCT02923115 | Completed Phase 1 Results DMC

• 2 other identifiers: DS1040-B-U1072015-005211-32
• Study Type: interventional
• Target: 134
• Locations: 8 countries
• Sites: 46

Brief 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.

Conditions

Pulmonary Embolism; Thrombotic Disease

Keywords

Venous thromboembolism (VTE); Pulmonary embolism (PE); Acute Submassive Pulmonary Embolism

Outcome Measures

Primary Outcomes (1)

• 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

  Clinically relevant bleeding was defined as major or clinically relevant non-major (CRNM) bleeding adjudicated by the Clinical Events Committee (CEC) based on International Society of Thrombosis and Haemostasis (ISTH) definitions and the CEC charter.

  Baseline up to Day 30 post infusion, up to approximately 3 years 2 months

Secondary Outcomes (5)

• 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

  Baseline to 12-72 hours post start of infusion, up to approximately 3 years 2 months

• 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

  Baseline to 12-72 hours post start of infusion, up to approximately 3 years 2 months

• 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

  Cohort 1: 0 up to 72 h post infusion; Cohorts 2 and 3: 0 up to 96 h post infusion; Cohort 4 and 5: 0 up to 120 h post infusion

• 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

  Cohort 1: 0 up to 72 h post infusion; Cohorts 2 and 3: 0 up to 96 h post infusion; Cohort 4 and 5: 0 up to 120 h post infusion

• 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

  Cohort 1: 0 up to 72 h post infusion; Cohorts 2 and 3: 0 up to 96 h post infusion; Cohort 4 and 5: 0 up to 120 h post infusion

Study Arms (2)

DS-1040b

EXPERIMENTAL

Participants who are randomized to receive DS-1040b as a single, continuous intravenous infusion (initial loading dose 3-6 mg). All participants will also receive standard of care anticoagulation enoxaparin therapy during the study drug infusion.

Drug: DS-1040b; Drug: Enoxaparin

Placebo

PLACEBO COMPARATOR

Participants who are randomized to receive placebo as a single, continuous intravenous infusion. All participants will also receive standard of care anticoagulation enoxaparin therapy during the study drug infusion.

Drug: Placebo; Drug: Enoxaparin

Interventions

DS-1040b DRUG

Single, continuous intravenous infusion over 12 to 24 hours (depending on cohort)

DS-1040b

Placebo DRUG

Single, continuous intravenous infusion of 0.9% sodium chloride over 12 to 24 hours

Placebo

Enoxaparin DRUG

Subcutaneous injection 1 mg/kg twice daily

DS-1040b; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 \< 90 mmHg for more than 15 consecutive minutes or a drop in 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.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (46)

Pulmonary Associates of Mobile

Mobile, Alabama, 36608, United States

Location

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

University of California, San Diego (UCSD) Medical Center

San Diego, California, 92103, United States

Location

Intercoastal Medical Group

Sarasota, Florida, 34239, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Mercury Street Medical

Butte, Montana, 59701, United States

Location

NYU Radiology Associate

New York, New York, 10016, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Duke University Medical Center (DUMC)

Durham, North Carolina, 27710, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Capital Area Research

Camp Hill, Pennsylvania, 17011, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Medical University Graz

Graz, 8036, Austria

Location

Medical University Innsbruck

Innsbruck, 6020, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

Universite Libre de Bruxelles (ULB) - Hopital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

University Hospital Leuven

Leuven, 3000, Belgium

Location

CHU de Brest - Hopital de la Cavale Blanche

Brest, 29609, France

Location

CHU Gabriel Montpied Clermont-Ferrand

Clermont-Ferrand, 63000, France

Location

CHU de Grenoble

La Tronche, 38700, France

Location

Hopital Europeen Georges Pompidou

Paris, 75017, France

Location

CHU St Etienne - Hopital Nord

Saint-Etienne, 42055, France

Location

Hopital Civil de Strasbourg

Strasbourg, 67091, France

Location

Staedtisches Klinikum Dresden-Friedrichstadt

Dresden, 01067, Germany

Location

Universitaetsklinikum Dresden

Dresden, 01307, Germany

Location

Universitaetsmedizin Greifswald

Greifswald, 17475, Germany

Location

Universitatsklinikum Magdeburg

Magdeburg, 39120, Germany

Location

Klinikum rechts der Isar, Technische Universität München

München, 81675, Germany

Location

AOU Ospedali Riuniti di Ancona

Ancona, 60126, Italy

Location

Universit degli Studi di Perugia - Azienda Ospedaliera di Perugia

Perugia, 06129, Italy

Location

Humanitas Research Hospital

Rozzano, 20089, Italy

Location

Ospedale di Circolo

Varese, 21100, Italy

Location

Noordwest Ziekenhuisgroep

Alkmaar, 1815 JD, Netherlands

Location

Academisch Medisch Centrum

Amsterdam, 1105 AZ, Netherlands

Location

Albert Schweitzer Hospital

Dordrecht, 3318 AT, Netherlands

Location

Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)

Leiden, 2333 ZA, Netherlands

Location

HagaZiekenhuis

The Hague, 2545 AA, Netherlands

Location

UMC Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital Universitario

Girona, 17007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Virgen del Rocío

Seville, 41014, Spain

Location

MeSH Terms

Conditions

Pulmonary Embolism; Venous Thromboembolism

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thromboembolism

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Clinical Study Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2016
• First Posted: October 4, 2016
• Study Start: June 23, 2016
• Primary Completion: August 5, 2019
• Study Completion: August 5, 2019
• Last Updated: April 19, 2023
• Results First Posted: July 30, 2020

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

BE (3); FR (6); NL (6); IT (4); AU (3); DE (5); US (15); ES (4)