Clinical trial NCT03486080: Study of Dutogliptin in Combination With Filgrastim in Post-Myocardial Infarction
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myocardial Infarction
Acute Myocardial Ischemia
STEMI - ST Elevation Myocardial Infarction
Lead sponsor: Recardio, Inc.
Sponsor class: INDUSTRY
First posted: 2018-04-03
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: 90 days
Secondary outcomes:
measure: Cardiovascular efficacy LVEF
timeFrame: 90 days
measure: Cardiovascular efficacy LVESV
timeFrame: 90 days
measure: Cardiovascular efficacy LVEDV
timeFrame: 90 days
measure: Cardiovascular tissue damage reduction
timeFrame: 90 days
measure: Cardiovascular LFM
timeFrame: 90 days
measure: Cardiovascular motion
timeFrame: 90 days
measure: Pharmacokinetics (PK)
timeFrame: 14 days
measure: Pharmacodynamics (PD)
timeFrame: 14 days
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Clinical department of Cardiology
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt am Wörthersee
city: Aalst
country: Belgium
facility: Algemeen Stedelijk Ziekenhuis Aalst
city: Budapest
country: Hungary
facility: Military Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinika
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Kardiológiai és Szívsebészeti Klinika
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
city: Bydgoszcz
country: Poland
facility: Nicolaus Copernicus University
city: Grodzisk Mazowiecki
country: Poland
facility: SPS Szpital Zachodni
city: Zamość
country: Poland
facility: Samodzielny Publiczny Szpital Wojewódzki im. Papieża Jana Pawła II
city: Łódź
country: Poland
facility: Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi ul. Pomorska 251
Study officials:
affiliation: Recardio, Inc.
name: Roman Schenk, MD
role: STUDY_CHAIR
References: