Pulmonary EmbolismPhase 1/2NCT02923115
Study to Assess the Safety, Pharmacokinetics/Dynamics of DS-1040b in Subjects With Acute Submassive Pulmonary Embolism
A Phase 1/2 study testing DS-1040b and Enoxaparin in people with Pulmonary Embolism and Thrombotic Disease, run by Daiichi Sankyo at 46 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Embolism, Thrombotic Disease
- What is being tested?
- DS-1040b and Enoxaparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 134 participants
- Where
- 46 sitesin 8 countries
- Study dates
- 23 Jun 2016to 5 Aug 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
46 sites in 8 countries.
46 sites in 8 countries
United States15 sites
Cedars-Sinai Medical Center
Beverly Hills, California, 90211
Massachusetts General Hospital
Boston, Massachusetts, 02114
Mercury Street Medical
Butte, Montana, 59701
Capital Area Research
Camp Hill, Pennsylvania, 17011
Northwestern Memorial Hospital
Chicago, Illinois, 60611
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Duke University Medical Center (DUMC)
Durham, North Carolina, 27710
University of Kentucky Medical Center
Lexington, Kentucky, 40536
Pulmonary Associates of Mobile
Mobile, Alabama, 36608
NYU Radiology Associate
New York, New York, 10016
Temple University Hospital
Philadelphia, Pennsylvania, 19140
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
University of California, San Diego (UCSD) Medical Center
San Diego, California, 92103
Intercoastal Medical Group
Sarasota, Florida, 34239
Jacobi Medical Center
The Bronx, New York, 10461
France6 sites
CHU de Brest - Hopital de la Cavale Blanche
Brest, 29609
CHU Gabriel Montpied Clermont-Ferrand
Clermont-Ferrand, 63000
CHU de Grenoble
La Tronche, 38700
Hopital Europeen Georges Pompidou
Paris, 75017
CHU St Etienne - Hopital Nord
Saint-Etienne, 42055
Hopital Civil de Strasbourg
Strasbourg, 67091
Netherlands6 sites
Noordwest Ziekenhuisgroep
Alkmaar, 1815 JD
Academisch Medisch Centrum
Amsterdam, 1105 AZ
Albert Schweitzer Hospital
Dordrecht, 3318 AT
Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)
Leiden, 2333 ZA
HagaZiekenhuis
The Hague, 2545 AA
UMC Utrecht
Utrecht, 3584 CX
Germany5 sites
Staedtisches Klinikum Dresden-Friedrichstadt
Dresden, 01067
Universitaetsklinikum Dresden
Dresden, 01307
Universitaetsmedizin Greifswald
Greifswald, 17475
Universitatsklinikum Magdeburg
Magdeburg, 39120
Klinikum rechts der Isar, Technische Universität München
München, 81675
Italy4 sites
AOU Ospedali Riuniti di Ancona
Ancona, 60126
Universit degli Studi di Perugia - Azienda Ospedaliera di Perugia
Perugia, 06129
Humanitas Research Hospital
Rozzano, 20089
Ospedale di Circolo
Varese, 21100
Spain4 sites
Hospital Universitario
Girona, 17007
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Clinico San Carlos
Madrid, 28040
Hospital Virgen del Rocío
Seville, 41014
Austria3 sites
Medical University Graz
Graz, 8036
Medical University Innsbruck
Innsbruck, 6020
Medical University of Vienna
Vienna, 1090
Belgium3 sites
Universite Libre de Bruxelles (ULB) - Hopital Erasme
Brussels, 1070
Cliniques Universitaires Saint-Luc
Brussels, 1200
University Hospital Leuven
Leuven, 3000
About this study
Official title: A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b When Added to Standard of Care Anticoagulation Therapy in Subjects With Acute Submassive Pulmonary Embolism
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
- Being tested
- DS-1040b, Placebo, Enoxaparin
- Keywords
- Venous thromboembolism (VTE), Pulmonary embolism (PE), Acute Submassive Pulmonary Embolism
- Medical subject headings
- Pulmonary Embolism, Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DS-1040bDrug
Single, continuous intravenous infusion over 12 to 24 hours (depending on cohort)
PlaceboDrug
Single, continuous intravenous infusion of 0.9% sodium chloride over 12 to 24 hours
EnoxaparinDrug
Subcutaneous injection 1 mg/kg twice daily
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo; Drug: Enoxaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The change from baseline in total thrombus volume was assessed by computed tomography angiography in segmental or larger pulmonary arteries following intravenous infusion of DS-1040b or placebo in addition to standard of care anti-coagulation therapy.
Measured: 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
Change in total pulmonary thrombus burden (total thrombus volume) was assessed by computed tomography pulmonary angiography (CTPA). All CTPA scans were evaluated by a central imaging laboratory in a blinded manner by radiologists.
Measured: 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
Plasma concentrations at each time point and PK parameter Cmax of DS 1040b was calculated using non-compartmental analysis.
Measured: 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
Plasma concentrations at each time point and PK parameter of Area Under the Concentration Versus Time Curve (0 to last) of DS-1040b was calculated using non-compartmental analysis.
Measured: 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
Plasma concentrations at each time point and PK parameter Terminal Half-life of DS-1040b was calculated using non-compartmental analysis.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2016 (estimated)
- Study start23 Jun 2016
- Primary completion5 Aug 2019
- Study completion5 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary EmbolismStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Study Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02923115
- Sponsor's protocol ID
- DS1040-B-U107
- Other IDs
- 2015-005211-32, 2015
- Status last verified
- Apr 2023
- First submitted
- 30 Sep 2016
- Last updated
- 19 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b When Added to Standard of Care Anticoagulation Therapy in Subjects With Acute Submassive Pulmonary Embolism
- ClinicalTrials.gov ID
- NCT02923115
- Acronym / sponsor ID
- DS1040-B-U107
- Conditions
- Pulmonary Embolism, Thrombotic Disease
- Keywords
- Venous thromboembolism (VTE), Pulmonary embolism (PE), Acute Submassive Pulmonary Embolism
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 23 Jun 2016 (actual)
- Primary completion
- 5 Aug 2019 (actual)
- Study completion
- 5 Aug 2019 (actual)
- First posted
- 4 Oct 2016 (estimated)
- Results
- Posted 30 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DS-1040b | Experimental | Drug: DS-1040b, Drug: EnoxaparinParticipants 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. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: EnoxaparinParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DS-1040bSingle, continuous intravenous infusion over 12 to 24 hours (depending on cohort) | Drug | DS-1040b |
| PlaceboSingle, continuous intravenous infusion of 0.9% sodium chloride over 12 to 24 hours | Drug | Placebo |
| EnoxaparinSubcutaneous injection 1 mg/kg twice daily | Drug | DS-1040b, Placebo |
Primary outcome
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
Time frame: Baseline up to Day 30 post infusion, up to approximately 3 years 2 months
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.
5 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Study Leader study director
Daiichi Sankyo
46 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DS-1040b and Enoxaparin in people with Pulmonary Embolism and Thrombotic Disease, run by Daiichi Sankyo at 46 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, France, Netherlands, Germany, Italy and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline up to Day 30 post infusion, up to approximately 3 years 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2023.