Dutogliptin in Co-administration With Filgrastim in Early Recovery Post-myocardial Infarction (HEAL-MI)

Phase 3, Randomized, Double-blind, Placebo-controlled, Safety and Efficacy Study of Dutogliptin in Co-administration With Filgrastim in Early Recovery Post-myocardial Infarction

The goal of this phase 3, randomized, double-blind, placebo-controlled clinical trial is to explore the safety and efficacy of dutogliptin administered subcutaneously (SC) in co-administration with filgrastim in adult patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

The primary objective is to evaluate the efficacy of dutogliptin compared with placebo in STEMI patients within 180 days of randomization measured by the time of first occurrence of a composite endpoint of cardiovascular (CV) death and worsening heart failure (HF) within 180 days. Participants will receive dutogliptin twice daily subcutaneously (SC) for 14 days and filgrastim (SC) daily for 5 days or placebo.

Study Overview

• Status: Not yet recruiting
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Dutogliptin + Filgrastim; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 4100
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, age 18 to 85 years (having reached 18 years of age and before having reached 86 years of age at the time of ICF signing)
2. Able to provide written informed consent, including signing and dating the ICF
3. STEMI is defined as follows:

Symptoms of myocardial ischemia (such as chest pain, shortness of breath, jaw pain, arm pain, diaphoresis, or any anginal equivalent) AND

Anterior STEMI:

• ECG Criteria

  • men > 40 years: ≥ 2 mm of new ST elevation in V2 and V3
  • men ≤ 40 years: ≥ 2.5 mm of new ST elevation in V2 and V3
  • women: ≥ 1.5 mm of new ST elevation in V2 and V3

• ECG Criteria

  o ≥ 1 mm of new ST elevation in two contiguous leads 4. STEMI must meet one of the following criteria:

• Anterior STEMI with thrombolysis in myocardial infarction (TIMI) 0 or 1 flow at presentation

• Non-anterior MI with the following:

  • TIMI 0 flow at presentation AND
  • Signs of HF, defined as at least one of the following radiographic evidence of pulmonary congestion, peripheral edema, increased jugular venous pressure, hepatojugular reflux or both, third heart sound or gallop 6. Female patients 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.

Exclusion Criteria:

1. Known significant pre-existing cardiomyopathy, moderate or severe mitral disease or aortic valvular disease
2. Known pre-existing left ventricular ejection fraction < 40%
3. Existing heart transplant
4. Treatment with any dipeptidyl peptidase 4 (DPP4) inhibitors (eg, alogliptin, lingliptin, vildagliptin, saxagliptin, sitagliptin) or granulocyte colony-stimulation factor (G-CSF) medication (eg, filgrastim, lenograstim, pegfilgrastim, lipegfilgrastim) within 4 months prior to randomization.
5. Contraindication to treatment with filgrastim, including known allergy to filgrastim or other G-CSF medication
6. Pregnant, planning to become pregnant, or nursing female patients
7. Known history of severe renal impairment or current renal impairment requiring dialysis
8. History of pancreatitis (induced by high doses of DPP-4 inhibitors)
9. Current or planned use of sulfonyl urea (risk of severe hypoglycemia)
10. Any clinically significant abnormality identified prior to randomization that in the judgement of the Investigator or Sponsor that would preclude safe completion of the study, or confound the anticipated benefit of dutogliptin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dutogliptin + Filgrastim; Participants will receive BID SC injections of 60 mg dutogliptin for 14 days in co-administration with 10 µg/kg filgrastim for 5 days.	Drug: Dutogliptin + Filgrastim; dutogliptin twice daily subcutaneously for 14 days and filgrastim daily subcutaneously for 5 days.
Placebo Comparator: Placebo-Dutogliptin + Placebo-Filgrastim; Randomized participants will receive BID SC injections of dutogliptin placebo for 14 days in co-administration with filgrastim placebo for 5 days.	Drug: Placebo; Placebo dutogliptin twice daily subcutaneously for 14 days and placebo filgrastim daily subcutaneously for 5 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of first occurence of the following composite endpoint of cardiovascular (CV) death and worsening of heart failure (HF)	defined as either an unplanned hospitalization or urgent visit resulting in intravenous therapy for heart failure	within 180 days of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Worsening heart failure	defined as either an unplanned hospitalization or urgent visit resulting in intravenous therapy for heart failure	within 180 days of randomization
Time to cardiovascular death	defined as the time from randomization to the date of cardiovascular death	within 180 days of randomization
Total symptom score of the Kansas City Cardiomyopathy Questionnaire		at 180 days

Collaborators and Investigators

• Sponsor: Recardio, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: May 19, 2023
• First Submitted That Met QC Criteria: May 19, 2023
• First Posted (Actual): May 31, 2023

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: REC-DUT-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No