NP202 for Treatment of Post -STEMI Left Ventricular Systolic Dysfunction

A Phase II Randomised, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Oral NP202 in Adults Who Have Left Ventricular Systolic Dysfunction Following Myocardial Infarction

NP202 is an experimental drug being developed by Armaron Bio Pty Ltd for potential use as a treatment for people after they have had a heart attack (MI).

Study Overview

• Status: Unknown
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Other: Placebo; Drug: NP202

Detailed Description

After someone has a MI, their heart 'remodels', which means that it changes in size and shape. This damage can lead to it being weaker and less efficient, and ultimately to major heart problems. There are some drugs currently available which help prevent remodelling and are used for treatment post-MI. However, there is still a high rate of remodelling and major heart problems in people post-MI. NP202 works in a different way to the drugs that are currently approved, and has been shown in animal studies to prevent post-MI remodelling.

This study will assess NP202 versus placebo on remodelling over a 3 month treatment period, with 1 month follow up

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2305
      • Recruiting
      • John Hunter Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have had a confirmed ST elevation myocardial infarction (STEMI) in the previous 5 days, which met all of the following criteria;

  • ≥ 0.2mV ST elevation in 2 or more V1 - V6 leads with presentation in a maximum of 12 hours of onset of symptoms
  • Troponin levels >10 x upper limit of normal (ULN) at the site's local laboratory.
  • Successful revascularisation by Percutaneous Coronary Intervention (PCI)
• Have left ventricular dysfunction post STEMI as evidenced by left ventricular ejection fraction (LVEF) ≤40% confirmed by echocardiogram at screening.
• Are receiving guideline-directed medical therapy for acute MI and post-MI left ventricular (LV) dysfunction according to national cardiology society/heart association STEMI guidelines.

Exclusion Criteria:

• Known cardiomyopathy or heart failure prior to MI.
• Cardiogenic shock and/or systolic blood pressure <85mmHg at Screening.
• Clinical history of ejection fraction ≤40% prior to this MI, or multiple prior MIs.
• Daily use of non-steroidal anti-inflammatory drugs (NSAIDs) and/or cyclooxygenase-2 (COX-2) inhibitors in the past month.
• Presence of device/hardware incompatible with MRI
• Estimated glomerular filtration rate (eGFR) <30ml/min
• Liver function tests 3 x ULN due to non-cardiac disease
• Have received any investigational research agent within 30 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product.

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
Experimental: NP202; 1000mg oral NP202 daily for 90 days	Drug: NP202; Active
Placebo Comparator: Placebo; Oral placebo daily for 90 days	Other: Placebo; Placebo; Other Names: Microcellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy as measured by Change from baseline in left ventricular end systolic volume index (LVESVi)	Change from baseline in left ventricular end systolic volume index (LVESVi) as assessed by MRI at 3 months	From baseline to 3 months post MI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy as measured by Change from baseline in LV end diastolic volume index (LVEDVi)	Change from baseline in LV end diastolic volume index (LVEDVi) as assessed by MRI at 3 months.	From baseline to 3 months post MI
Efficacy as measured by Change from baseline in LV ejection fraction (LVEF)	Change from baseline in LVEF as assessed by MRI at 3 months.	From baseline to 3 months post MI
Efficacy as measured by Change from baseline in LV diastolic function	Changes from baseline in LV diastolic function based on LV peak filling rate as assessed by MRI at 3 months.	From baseline to 3 months post MI
Efficacy as measured by Change from baseline in relative infarct size	Change from baseline in relative infarct size as a percent of LV mass as assessed by late contrast enhancement MRI at 3 months.	From baseline to 3 months post MI

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by occurrence of adverse events (AE)	All AE occurring during the study will be recorded	From baseline to end of study (4 months)
Safety as assessed by changes in laboratory results	Biochemistry, haematology, prostate specific antigen (PSA), urinalysis	At Baseline, Week 2, and Months 1, 2, 3 and 4
Safety as assessed by changes in physical examination	Changes in physical examination finding including vital signs (heart rate, blood pressure, respiratory rate, temperature)	At Baseline, Week 2, and Months 1, 2, 3 and 4
Safety as assessed by changes in 12-lead electrocardiograms (ECGs).	Changes in ECG intervals	At Baseline, Week 2, and Months 1, 2, 3 and 4
Trough levels of NP202 in plasma	Concentrations of NP202 in plasma in a subset of 30 subjects.	At Baseline, Week 2 and at Months 1, 2 and 3
Efficacy as assessed by laboratory biomarkers	Absolute values and changes from baseline in serum biomarker levels (Troponin I, Troponin T, high sensitivity C reactive protein (hs-CRP) and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP)	At Baseline and Months 1, 2 and 3

Collaborators and Investigators

• Sponsor: Armaron Bio Pty Ltd
• Investigators: Study Director: Grant McLachlan, Sponsor GmbH

Publications and helpful links

General Publications

• Boyle AJ, Schultz C, Selvanayagam JB, Moir S, Kovacs R, Dib N, Zlotnick D, Al-Omary M, Sugito S, Selvarajah A, Collins N, McLachlan G. Calcium/Calmodulin-Dependent Protein Kinase II Delta Inhibition and Ventricular Remodeling After Myocardial Infarction: A Randomized Clinical Trial. JAMA Cardiol. 2021 Jul 1;6(7):762-768. doi: 10.1001/jamacardio.2021.0676.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): February 1, 2018

Study Registration Dates

• First Submitted: September 7, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimate): September 23, 2015

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

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
• Other Study ID Numbers: NP202-002; ACTRN12615000609550 (Registry Identifier: Australian New Zealand Clinical Trials Registry)