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Study of Dutogliptin in Combination With Filgrastim in Post-Myocardial Infarction

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ClinicalTrials.gov Identifier: NCT03486080
Recruitment Status : Recruiting
First Posted : April 3, 2018
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Recardio, Inc.

Brief Summary:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study of Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction

Condition or disease Intervention/treatment Phase
Acute Myocardial Infarction Acute Myocardial Ischemia STEMI - ST Elevation Myocardial Infarction Drug: Dutogliptin Tartrate Drug: Filgrastim Injectable Product Drug: Placebos Phase 2

Detailed Description:

Dutogliptin 60 mg administered by twice daily subcutaneous (SC) injection for 14 days in combination with a fixed standard dose of filgrastim (10 µg/kg) administered SC daily for 5 days. This study will be conducted in adults with ST-elevation myocardial infarction (STEMI) with successful revascularization following percutaneous coronary intervention (PCI) and stent implantation.

Primary Objective

• To evaluate the safety and tolerability of dutogliptin in combination with filgrastim in subjects with STEMI compared with placebo

Secondary Objectives

  • To assess preliminary efficacy of dutogliptin in combination with filgrastim in subjects with STEMI compared with placebo as determined by cardiac magnetic resonance imaging (cMRI)
  • To determine the pharmacokinetics (PK) of dutogliptin in a subset of the study population
  • To establish the pharmacodynamics (PD) of dutogliptin (plasma DPP4 activity) in a subset of the study population

Exploratory Objectives

  • To examine the effects of dutogliptin in combination with filgrastim on:
  • Change from baseline in plasma stromal cell-derived factor (SDF)-1a levels
  • Change from baseline in plasma biomarkers, including N-terminal pro-b-type natriuretic peptide (NT-proBNP) and high sensitivity troponin

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Blinded placebo controlled
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study of Dutogliptin in Combination With Filgrastim in Early Recovery Post-Myocardial Infarction
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
Active Comparator: Dutogliptin/filgrastim combination
Twice daily SC injections of 60 mg dutogliptin tartrate for 14 days in combination with 10 µg/kg filgrastim injectable product for 5 days
Drug: Dutogliptin Tartrate
Active treatment
Other Name: dutogliptin

Drug: Filgrastim Injectable Product
Active treatment
Other Name: filgrastim

Placebo Comparator: Placebo control
Twice daily dutogliptin SC placebos for 14 days in combination with matching filgrastim SC placebos for 5 days
Drug: Placebos
placebo control
Other Name: placebo




Primary Outcome Measures :
  1. Safety assessment of the number of Grade 3 and 4 treatment emergent AEs or serious AEs (SAEs) as assessed by CTCAE v4.0.AEs (SAEs) as assessed by CTCAE v4.0. [ Time Frame: 90 days ]
    Assess the tolerability of a combination of dutogliptin and filgrastim


Secondary Outcome Measures :
  1. Cardiovascular efficacy LVEF [ Time Frame: 90 days ]
    Left ventricular ejection fraction (%) by MRI

  2. Cardiovascular efficacy LVESV [ Time Frame: 90 days ]
    Left ventricular end systolic volume (mL) by MRI

  3. Cardiovascular efficacy LVEDV [ Time Frame: 90 days ]
    Left ventricular end diastolic volume (mL) by MRI

  4. Cardiovascular tissue damage reduction [ Time Frame: 90 days ]
    Infarct size (mm2)

  5. Cardiovascular LFM [ Time Frame: 90 days ]
    Left ventricular mass (mm2)

  6. Cardiovascular motion [ Time Frame: 90 days ]
    Regional wall motion (mm)

  7. Pharmacokinetics (PK) [ Time Frame: 14 days ]
    Assess the systemic exposure (dutogliptin AUC) of s.c. administered dutogliptin

  8. Pharmacodynamics (PD) [ Time Frame: 14 days ]
    Assess the PD effects (plasma DPP4 activity) of s.c. administered dutogliptin



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 1. Male or female born between 1933 and 2000.
  2. Body weight <96 kg (212 lb).
  3. Able to provide written informed consent, including signing and dating the informed consent form (ICF).
  4. Diagnosis of STEMI (defined as new ST-segment elevation at the J point of at least 2 continuous leads of >2 mm [0.2 mV] in men or >1.5 mm [0.1 mV] in women in leads V2 and V3 OR >1 mm in any other contiguous precordial leads or the limb leads [for both men and women]) with PCI (bare metal or drug-eluting stent) and Thrombolysis in Myocardial Infarction flow grade 2 or 3 occurring >2 hours and <24 hours after symptom onset.
  5. LVEF ≤45% obtained by cECHO performed within 36 hours post-stent placement.
  6. Receiving standard medical therapy for post-MI treatment, according to local procedures and Principal Investigator discretion
  7. Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and an additional negative urine pregnancy test prior to the first dose of IMP unless regulated differently by national legislation.
  8. Sexually active female subjects of childbearing potential (i.e., women who are not postmenopausal or who have not had a bilateral oophorectomy, hysterectomy, or tubal ligation) and all male subjects (who have not been surgically sterilized by vasectomy) must agree to use effective contraception during the study.

Exclusion criteria

  1. Previous MI prior to Screening.
  2. Complex peri/post-MI clinical course, including arrhythmias, cardiogenic shock, pulmonary edema requiring mechanical ventilation, or requirement for vasopressor medications.
  3. Significant pre-existing cardiomyopathy with known LVEF ≤45% or moderate to severe mitral or aortic valvular disease.
  4. Amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
  5. Existing heart transplant.
  6. Ventricular tachycardia or fibrillation not associated with an acute ischemic episode.
  7. Uncontrolled hypertension (systolic >180 mmHg or diastolic >120 mmHg).
  8. Treatment with any DPP4 inhibitors (e.g., alogliptin, linagliptin, vildagliptin, saxagliptin, sitagliptin) or G-CSF medication (e.g., filgrastim, lenograstim, pegfilgrastim, lipegfilgrastim) within 4 months prior to Randomization.
  9. Contraindication to treatment with filgrastim, including known allergy to filgrastim or other G-CSF medication.
  10. Anemia defined as hemoglobin <9 g/dL prior to Randomization.
  11. Thrombocytosis (platelets >500 k/µL).
  12. Known positive serology for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
  13. Alanine aminotransferase (ALT) concentrations >3 times the upper limit of normal (ULN) or bilirubin >2 x ULN prior to Randomization, according to local laboratory assessments.
  14. History of cirrhosis and Child-Pugh score B or C.
  15. Current fever greater than 101.4 °F (38.6 °C) or recent systemic infection within 2 weeks prior to Randomization.
  16. Contraindication to cMRI procedure, including prior implantable cardioverter defibrillator placement, known reaction to gadolinium, claustrophobia, non-MRI-compatible, cochlear implant, morbid obesity, or presence of ferromagnetic material including shunts, shrapnel, penile prostheses, or blood vessel coil.
  17. Pregnant, planning to become pregnant, or nursing female subjects.
  18. Autoimmune disease requiring immunosuppressive therapy or chronic steroid treatment >5 mg/day prednisolone or equivalent.
  19. Significant renal impairment defined as estimated glomerular filtration rate <45 mL/min/1.73 m2, using the Chronic Kidney Disease Epidemiology Collaboration equation.
  20. Active neoplasm requiring surgery, chemotherapy, or radiation within the prior 12 months (subjects with a history of malignancy who have undergone curative resection or otherwise not requiring treatment for at least 12 months prior to Screening with no detectable recurrence are allowed).
  21. Malignant hematological disease, i.e., chronic myeloid leukemia or myelodysplastic syndrome.
  22. History of cerebrovascular accident or transient ischemic attack in the past 6 months.
  23. History of pneumonia in the last 4 weeks.
  24. History of any significant medical or psychiatric disorder that in the opinion of the investigator would make the subject unsuitable for participation in the study.
  25. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) or treatment with an investigational biologic drug within 6 weeks prior to randomization.
  26. Participation in another concurrent clinical trial involving a therapeutic intervention (participation in observational studies and/or registry studies is permitted).
  27. Unable or unwilling to comply with the requirements of the study.
  28. Subject and/or an immediate family member is an employee of the investigational site directly affiliated with this study, the sponsor or the contract research organization.
  29. Considered by the investigator to be unsuitable to participate in the study for any other reason.
  30. Persons who are in an institution as a result of an administrative or judicial order, or soldiers.
  31. History of alcohol or drug abuse.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03486080


Contacts
Contact: Roman Schenk, MD 415 707-0592 rs@recardio.eu
Contact: Darrell Nix, Ph.D. 415-429-5991 dn@recardio.eu

Locations
United States, California
Cedars-Sinai Medical Center, Heart Institute Not yet recruiting
Los Angeles, California, United States, 90048
Contact: Melissa Pozun    916-533-1603    Melissa.Pozun@veristat.com   
Principal Investigator: Timothy Henry, MD         
Scripps Clinical Medical Group Not yet recruiting
San Diego, California, United States, 92101
Contact: Melissa Pozun    916-533-1603    Melissa.Pozun@veristat.com   
Principal Investigator: Richard A Shatz, MD         
Stanford University Not yet recruiting
Stanford, California, United States, 94305
Contact: Melissa Pozun    916-533-1603    Melissa.Pozun@veristat.com   
Principal Investigator: Phillip Yang, MD         
United States, Minnesota
Abbott Northwestern Hospital-Minneapolis Heart Institute Not yet recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Melissa Pozun         
Contact    916-533-1603    Melissa.Pozun@veristat.com   
Principal Investigator: Jay H Travese, MD         
United States, North Carolina
Duke University Not yet recruiting
Durham, North Carolina, United States, 27701
Contact: Melissa Pozun    916-533-1603    Melissa.Pozun@veristat.com   
Principal Investigator: Thomas J Povsic, MD, Ph.D.         
Austria
Clinical department of Cardiology Recruiting
Graz, Austria
Contact: Frederique Lecomte    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Dirk von Lewinski, MD         
Clinical department of Cardiology Recruiting
Linz, Austria
Contact: Frederique Lecomte    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Regina Steringer-Mascherbauer, MD         
Belgium
Algemeen Stedelijk Ziekenhuis Aalst Recruiting
Aalst, Belgium
Contact: Frederique Lecomte    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Ian Buysschaert, MD         
Zna Middelheim Not yet recruiting
Antwerp, Belgium
Contact: Frederique Lecomte    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Paul Vermeersch, MD         
Bulgaria
Acibadem City Clinic Tokuda Hospital Not yet recruiting
Sofia, Bulgaria
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Valeri Gelev, MD         
Acibadem CityClinic Not yet recruiting
Sofia, Bulgaria
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Ivo Petrov, MD         
University Multiprofile Hospital for Active Treatment and Emergency Medicine N.I.Pirogov Not yet recruiting
Sofia, Bulgaria
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Mariya Milanova, MD         
Hungary
Military Hospital Not yet recruiting
Budapest, Hungary
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Róbert Gábor Kiss, MD         
Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinika Not yet recruiting
Budapest, Hungary
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Béla Merkely, MD         
Debreceni Egyetem Kardiológiai és Szívsebészeti Klinika Not yet recruiting
Debrecen, Hungary
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Istvan Édes, MD         
Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház Recruiting
Miskolc, Hungary
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Geregly Nagy, MD         
PTE ÁOK Szívgyógyászati Klinika Not yet recruiting
Pécs, Hungary
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Iván Horváth, MD         
Zala Megyei Szent Rafael Kórház Not yet recruiting
Zalaegerszeg, Hungary
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Géza Lupkovics, MD         
Netherlands
Zuyderland Medisch Centrum Not yet recruiting
Geleen, Netherlands
Contact: Frederique Lecomte         
Contact    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Bas Kietselaer, MD         
University Medical Center Groningen Not yet recruiting
Groningen, Netherlands
Contact: Frederique Lecomte    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Pim Van der Harst, MD         
MUMC Not yet recruiting
Maastricht, Netherlands
Contact: Frederique Lecomte    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Arnoud van't Hof, MD         
Maasstad Ziekenhuis Not yet recruiting
Rotterdam, Netherlands
Contact: Frederique Lecomte    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Peter Smits, MD         
Zuyderland medisch centrum Not yet recruiting
Sittard, Netherlands
Contact: Frederique Lecomte    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Bas Kietselaer, MD         
Isala Not yet recruiting
Zwolle, Netherlands
Contact: Frederique Lecomte    +43 678 13 22 033    Frederique.Lecomte@qbex.at   
Principal Investigator: Jorik Timmer, MD         
Poland
Nicolaus Copernicus University Not yet recruiting
Bydgoszcz, Poland
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Jacek Kubica, MD         
SPS Szpital Zachodni Not yet recruiting
Grodzisk Mazowiecki, Poland, 05-825
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Maciej Zarebinski, MD         
Górnośląskie Centrum Kardiologii Szpital w Ochojcu Not yet recruiting
Katowice, Poland
Contact: Adam Mickiewicz         
Contact    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Wojciech Wojakowski, MD         
Samodzielny Publiczny Szpital Wojewódzki im. Papieża Jana Pawła II Not yet recruiting
Zamość, Poland
Contact: Adam Mickiewicz         
Contact    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Andrzej Kleinrok, MD         
Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi ul. Pomorska 251 Not yet recruiting
Łódź, Poland, 92-213
Contact: Adam Mickiewicz    0048605300571    adam.mickiewicz@altiora-cro.net   
Principal Investigator: Pawel Ptaszynski, MD         
Sponsors and Collaborators
Recardio, Inc.
Investigators
Study Chair: Roman Schenk, MD Recardio, Inc.

Additional Information:
Responsible Party: Recardio, Inc.
ClinicalTrials.gov Identifier: NCT03486080     History of Changes
Other Study ID Numbers: REC-DUT-002
First Posted: April 3, 2018    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Myocardial Ischemia
Coronary Artery Disease
ST Elevation Myocardial Infarction
Pathologic Processes
Necrosis
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs