Clinical trial NCT02557217: NP202 for Treatment of Post -STEMI Left Ventricular Systolic Dysfunction
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: ST Elevation Myocardial Infarction
Lead sponsor: Armaron Bio Pty Ltd
Sponsor class: INDUSTRY
First posted: 2015-09-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy as measured by Change from baseline in left ventricular end systolic volume index (LVESVi)
timeFrame: From baseline to 3 months post MI
Secondary outcomes:
measure: Efficacy as measured by Change from baseline in LV end diastolic volume index (LVEDVi)
timeFrame: From baseline to 3 months post MI
measure: Efficacy as measured by Change from baseline in LV ejection fraction (LVEF)
timeFrame: From baseline to 3 months post MI
measure: Efficacy as measured by Change from baseline in LV diastolic function
timeFrame: From baseline to 3 months post MI
measure: Efficacy as measured by Change from baseline in relative infarct size
timeFrame: From baseline to 3 months post MI
Other outcomes:
measure: Safety as assessed by occurrence of adverse events (AE)
timeFrame: From baseline to end of study (4 months)
measure: Safety as assessed by changes in laboratory results
timeFrame: At Baseline, Week 2, and Months 1, 2, 3 and 4
measure: Safety as assessed by changes in physical examination
timeFrame: At Baseline, Week 2, and Months 1, 2, 3 and 4
measure: Safety as assessed by changes in 12-lead electrocardiograms (ECGs).
timeFrame: At Baseline, Week 2, and Months 1, 2, 3 and 4
measure: Trough levels of NP202 in plasma
timeFrame: At Baseline, Week 2 and at Months 1, 2 and 3
measure: Efficacy as assessed by laboratory biomarkers
timeFrame: At Baseline and Months 1, 2 and 3
Locations:
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
Study officials:
affiliation: Sponsor GmbH
name: Grant McLachlan
role: STUDY_DIRECTOR
References:
citation: 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.