Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b in Subjects With Acute Ischemic Stroke

NCT02586233 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: DS1040-A-U1032015-001824-43
• Study Type: interventional
• Target: 106
• Locations: 11 countries
• Sites: 55

Brief Summary

This is a Phase 1b/2, double-blind (study participants and Investigators), placebo-controlled, randomized, single-ascending dose, multi-center study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040b in participants with Acute Ischemic Stroke (AIS).

Conditions

Acute Ischemic Stroke; Thrombotic Disease

Keywords

Acute Ischemic Stroke; Thrombotic disease; DS-1040b

Outcome Measures

Primary Outcomes (1)

• Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke

  Treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during the treatment period (from first dose date until 30 days after the last dosing date), having been absent at predose; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-dose state, when the adverse event is continuous.

  Baseline up to 90 days post last dose, up to 3 years 11 months

Secondary Outcomes (6)

• Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke

  Predose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours postdose

• Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke

  Predose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours postdose

• Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke

  Pre-dose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours post-dose

• Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke

  Baseline and 6 hours postdose

• Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke

  30 days post dose

Study Arms (2)

DS-1040b

EXPERIMENTAL

Participants who will be randomized to receive intravenous (IV) infusion of DS-1040b ranging from 0.6 mg to 9.6 mg.

Drug: DS-1040b

Placebo

PLACEBO COMPARATOR

Participants who will be randomized to receive intravenous (IV) infusion of placebo.

Drug: Placebo

Interventions

DS-1040b DRUG

DS-1040b for IV infusion (0.6 mg to 9.6 mg) over 6-hour period

Also known as: Experimental product

DS-1040b

Placebo DRUG

0.9% sodium chloride (placebo comparator) for IV infusion over 6-hour period

Placebo

Eligibility Criteria

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

You may qualify if:

• Has a clinical diagnosis of acute ischemic stroke (including lacunar stroke/infarct) supported by computed topography or magnetic resonance imaging to rule out alternative cause for presenting symptoms
• Has onset of stroke symptoms within 4.5 to 12 hours before initiation of study drug administration - for subjects with a stroke upon waking, time of symptom onset is the last time the subject was known to be well
• Has a NIHSS score of ≥ 2 (for Cohorts 1-5) and ≥ 5 (for Cohort 6)
• Has Low dose heparin or low molecular weight heparin at a preventive dose are allowed from 24 hours after treatment start completion and after confirmation of no intracranial bleeding on the 24-hours repeat brain imaging.
• Is a Cohort 6 participant who is treated or anticipated to be treated with intra-arterial therapy (IAT) for ischemic stroke at the time of randomization (for enrollment in the IAT subgroup)
• Has given written informed consent to participate in the study prior to participating in any study-related procedures - depending on country-specific practice, written informed consent may be acceptable from legally authorized representative
• Has given a separate written informed consent for collecting a blood sample for genotyping

You may not qualify if:

• Is a Cohort 1-5 participant who has been treated or is going to be treated with tissue plasminogen activator (tPA) and/or endovascular thrombectomy during current stroke
• Is a Cohort 6 participant treated or anticipated to be treated with tPA during current stroke
• Has evidence of intracranial hemorrhage on non-contrast computed tomography (CT/CAT) scan or magnetic resonance imaging (MRI)
• Has symptoms of subarachnoid hemorrhage, even with normal imaging
• Has an Alberta Stroke Program Early CT Score (ASPECTS) \<6
• Has prior non-traumatic intracranial hemorrhage (excluding microhemorrhages observed in imaging)
• Has known arteriovenous malformation or aneurysm
• Has evidence of active bleeding
• Has platelet count less than 100,000
• Has International Normalized Ratio greater than 1.7
• Has used unfractionated heparin within 24 hours prior to treatment and has an elevated partial thromboplastin time
• Has used a non-vitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 24 hours before treatment
• Has used fondaparinux or low molecular weight heparin at an anticoagulation dose within 24 hours prior to treatment
• Has anticipated use of an anticoagulation dose of heparin, or fondaparinux or low molecular weight heparin, or nonvitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 48 hours after completion of study drug treatment (low dose heparin or low molecular weight heparin at a preventive dose are allowed from 24 hours after treatment completion and after confirmation of no intracranial bleeding on the 24 hours repeat brain imaging. In Cohort 6, heparin treatment associated with IAT is allowed.)
• Has blood pressure \> 185/110 mmHg, or requires aggressive medication to maintain blood pressure below this limit (routine medical treatment including IV drug treatment is allowed to lower the blood pressure below this limit)

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (55)

University of South Alabama USA Health System

Mobile, Alabama, 36604, United States

Location

UCLA Medical Center Stroke Network

Los Angeles, California, 90024, United States

Location

UC Health Memorial Hospital

Colorado Springs, Colorado, 80909, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

JFK Neuroscience Institute

Edison, New Jersey, 08820, United States

Location

Icahn School Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Duke University Health System

Durham, North Carolina, 27710, United States

Location

OSU - Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health Sciences University Hospital

Portland, Oregon, 97239, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Palmetto Health, USC School of Medicine

Columbia, South Carolina, 29203, United States

Location

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, 37403, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

Location

Royal Adelaide Hospital Neurology Dept.

Adelaide, South Australia, 5000, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

St. Annes University Hospital

Brno, Czechia

Location

Vitkovicka nemocnice a.s. Zaluzanskeho

Ostrava Vitkovice, Czechia

Location

CHRU Besançon - Hôpital Jean Minjoz

Besançon, 25000, France

Location

Hôpital Pellegrin - CHU Bordeaux

Bordeaux, 33000, France

Location

CHRU Lille - Hôpital Roger Salengro

Lille, 59037, France

Location

Klinikum Altenburger Land

Altenburg, 04600, Germany

Location

Universittsklinikum Essen AR Klinik fr Neurologie

Essen, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universitat

Frankfurt am Main, Germany

Location

Ospedale di Citta di Castello

Città di Castello, 06018, Italy

Location

Ospedale di Branca Largo Unita d'Italia

Gubbio, 06024, Italy

Location

Ospedale Guglielmo da Saliceto Via Taverna

Piacenza, 29121, Italy

Location

Ospedaliero di Albenga - Pietra Ligure Dept Neurology

Pietra Ligure, 17027, Italy

Location

Azienda Ospedaliero Universitaria

Pisa, 56126, Italy

Location

Ospedale Borgo Trento

Verona, 37121, Italy

Location

Svet zdravia a.s.,Vseobecna nemocnica Rimavska Sobota

Rimavská Sobota, Slovakia

Location

NsP Spisska Nova Ves

Spišská Nová Ves, Slovakia

Location

Pusan National University Hospital

Busan, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Hospital de la santa creu i sant pau C

Barcelona, Spain

Location

Vall d'Hebron Hospital

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Hospital Virgen del Rocio

Seville, Spain

Location

Hospital Clinico Universitario de Valladolid

Valladolid, Spain

Location

Hospital Clinico Universitario Lozano Blesa de Zaragoza

Zaragoza, Spain

Location

Chang Gung Memorial Hospital-Linkou Branch

Taoyuan District, Hsien, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

University College Hospitals NHS Foundation Trust

London, England, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, Scotland, United Kingdom

Location

Salford Royal Hospital

Salford, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, United Kingdom

Location

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

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

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical 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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 26, 2015
• Study Start: September 1, 2015
• Primary Completion: August 13, 2019
• Study Completion: August 13, 2019
• Last Updated: September 9, 2020
• Results First Posted: September 9, 2020

Record last verified: 2020-08

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

SL (2); GB (4); FR (3); TW (4); KR (3); CZ (2); DE (3); IT (6); US (16); ES (8); AU (4)