A clinical study in humans of a new drug (dutogliptin) with an existing drug (filgrastim) for use after a heart attack.
- Conditions
- Acute myocardial infarction, acute myocardial ischemia, STEMI ST elevation myocardial infarctionTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2018-000916-75-PL
- Lead Sponsor
- RECARDIO Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 140
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.Left ventricular ejection fraction (LVEF) =45% obtained by cECHO performed within 36 hours post-stent placement.
6.Receiving standard medical therapy for post-myocardial infarction (MI) treatment, according to local procedures and PI 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40
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 granulocyte-colony stimulating factor 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/uL).
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 101.4F (38.6C) 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, 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 sit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and tolerability of dutogliptin in combination with filgrastim in subjects with STEMI compared with placebo;Secondary Objective: •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)<br>•To determine the pharmacokinetics (PK) of dutogliptin in a subset of the study population<br>•To establish the pharmacodynamics (PD) of dutogliptin (plasma DPP4 activity) in a subset of the study population<br>;Primary end point(s): Safety assessments will include reporting of AEs and serious AEs (SAEs), clinical laboratory tests, ECGs, vital signs, and physical examinations.;Timepoint(s) of evaluation of this end point: 90 days
- Secondary Outcome Measures
Name Time Method