DS-9231 in Intermediate-risk (Sub-massive) Acute Pulmonary Embolism (PE)

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate safety and initial effectiveness of DS-9231 when taken together with current standard of care. Evaluation will be done with low, medium and then high doses of DS-9231 versus placebo, in participants with medium-risk acute pulmonary embolism.

Official Title
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Evaluation of Safety and Thrombolytic Effect of Ascending Doses of DS-9231 (TS23) in Subjects With Intermediate-risk (Sub-massive) Acute Pulmonary Embolism (PE)

Conditions
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Pulmonary Embolism

Intervention / Treatment
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* Drug: DS-9231
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Had protocol-defined pulmonary embolism (PE) Has stable systolic blood pressure (SBP) >90 mm Hg Has evidence of right ventricular (RV) dysfunction Has executed informed consent Exclusion Criteria: Has history or plans for thrombotic therapy outside protocol allowance Has other contraindications for participation Has laboratory results outside protocol-specified limits Is pregnant, nursing, and/or not willing or able to use protocol-defined contraceptives Has history or condition, or participated in another investigational study that (per protocol or in the opinion of the investigator) might compromise: the safety or well-being of the participant or the participant's offspring the safety of study staff the analysis of results

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Ascending doses in sequential cohorts (1-3) will be evaluated against placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DS-9231<br>In conjunction with standard of care, participants will receive an intravenous infusion delivering DS-9231 at ascending dose levels in Cohort 1, 2, and 3 | Drug: DS-9231<br>* DS-9231 in saline solution for intravenous infusion<br>* Other names: Investigational product;|
| Placebo Comparator: Placebo<br>In conjunction with standard of care, participants will receive an intravenous infusion delivering only saline solution as matching placebo comparator | Drug: Placebo<br>* Placebo is matching saline solution for intravenous infusion<br>* Other names: Matching placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in total thrombus volume |  | Baseline, 48-96 hours after study drug administration | 
| Percentage of participants with various gradations of decrease in total thrombus volume |  | Baseline, 48-96 hours after study drug administration | 
| Number of participants with major or clinically relevant nonmajor bleeding |  | within 7 days after study drug administration | 
| Number of participants with adverse events |  | within 30 days after study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in total thrombus volume |  | Baseline, 30 days after study drug administration | 
| Percentage of participants with with various gradations of decrease in total thrombus volume |  | 30 days after study drug administration | 
| Percent change from baseline in RV/ left ventricle (LV) diameter ratio |  | Baseline, 48-96 hours and 30 days after study drug administration | 
| Number of participants with PE-related deaths |  | within 30 days after study drug administration | 
| Number of participants who died from any cause |  | within 30 days after study drug administration | 
| Percentage of participants with clinical deterioration requiring additional rescue therapy for PE |  | within 30 days after study drug administration | 
| Number of participants with with recurrent, objectively documented venous thromboembolism (VTE) |  | within 30 days after study drug administration | 
| Participant-reported quality of life on a proprietary scale |  | Baseline, Day 30 after study drug administration | 
| Number of participants with major or clinically relevant nonmajor bleeding |  | within 30 days after study drug administration | 
| Number of participants re-hospitalized for any reason |  | within 30 days after study drug administration | 
| Number of participants with non-bleeding adverse events (AEs) |  | within 30 days after study drug administration | 
| Number of participants with anti-drug antibodies (ADAs) |  | within 30 days after study drug administration | 
| Plasma concentration of DS-9231 |  | Baseline to 30 days after study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sub-massive acute pulmonary embolism