The main goal of this study is to evaluate efficacy of a single administration of ATH3G10 in patients presenting with an acute STEMI undergoing PCI.The primary objective is to investigate effects on left ventricular remodelling as measured by the…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: Left Ventricular End-Diastolic Volume index (LV EDVi) change
from Visit 2 to Visit 3.
Safety endpoints: Safety and tolerability: AEs/SAEs, blood pressure, physical
examination, ECG and laboratory assessments including clinical chemistry,
haematology and coagulation.
Secondary outcome
Secondary endpoints: Myocardial Salvage index (MSi) at Visit 2.
Background summary
The present study ATH3G10-006 aims to investigate efficacy and safety in
patients that have suffered a STEMI. The current experimental data suggest that
ATH3G10 may reduce infarct size and left ventricular remodelling. Thus, ATH3G10
may reduce risk for heart failure development if it can be administered to
STEMI patients that has suffered a major anterior wall infarction or where
coronary blood flow is less than normal in spite of successful PCI. These
patients are at high risk for later complications and there are today no
medical treatments that specifically reduce risk in these patients. The acute
inflammatory reaction in conjunction with a STEMI and reperfusion by PCI has an
acute onset and last for several weeks. The signals leading to the final size
of the infarction and to left ventricular remodelling is established during
this time. Therapies aiming to block these reactions should thus last over this
period. ATH3G10 is an IgG1 antibody, and its pharmacokinetic properties are
such that a single dose will lead to a relevant exposure over the entire period
of interest. To cover the entire period of post-infarction inflammation, the
drug should be given as soon as possible when reduced TIMI flow has been noted.
Study objective
The main goal of this study is to evaluate efficacy of a single administration
of ATH3G10 in patients presenting with an acute STEMI undergoing PCI.
The primary objective is to investigate effects on left ventricular remodelling
as measured by the change in end diastolic volume measured by MRI.
The safety objectives are to investigate the safety and tolerability of ATH3G10.
The secondary objective is to investigate effects on myocardial salvage index
(MSi) measured by MRI
Study design
Phase IIa, placebo-controlled, double-blind, randomized multicenter pilot study
Intervention
Patients will be allocated to receive either 250mg ATH3G10 or matching placebo
given as a single dose within 120 minutes of the start of the PCI procedure.
Study burden and risks
Potential study patients will be identified in the hospital catheterisation
laboratory at the study sites where PCI procedure is performed. In connection
with PCI procedure, the patients will be informed about the study. The patients
need to consent to study participation before any study specific assessments
are performed.
After confirmation of fulfilled eligibility criteria, the patient will be
randomised to treatment with 250 mg of ATH3G10 (corresponding to approximately
2-4 mg/kg) or placebo and the study medication will be administered as soon as
possible after randomisation and within 120 minutes of start of the PCI
procedure. Blood samples for safety (clinical chemistry, haematology and
coagulation), drug concentration analysis, immunogenicity, cardiac samples
(TnT, BNP and CRP) and protein biomarkers will be drawn pre-dose. Blood
pressure and ECG will be assessed pre-dose and through-out the visit. Blood
samples for safety will be drawn at 8, 16 and 24 hours post-dose.
At Visit 2, within 24-72 hours of performed PCI procedure, an MRI examination
will be performed and again blood will be drawn. The patients will then be
monitored for adverse events and otherwise treated in hospital according to
clinical practice until discharged.
An outpatient 3-month follow-up visit will be performed with clinical and
adverse event evaluation and blood will be drawn, and a second MRI examination
will be performed. The patient will answer a quality of life questionnaire in
connection with the visit.
The patients will be contacted by telephone at 6 and 12 months(last visit) for
adverse event reporting including cardiovascular events of special interest and
concomitant medication. The patient will also answer a quality of life
questionnaire in connection with the 12-month follow-up visit.
The current study is designed to be a well-controlled study investigating
efficacy of ATH3G10 in patients suffering poor perfusion at PCI for STEMI and
to further evaluate safety and tolerability of the drug. The study will be
double blind to minimize bias.
The single dose slow intravenous injection of 250 mg ATH3G10 is expected to
result in relevant plasma levels in patients in the planned study. The dose is
selected based on pharmacokinetic data from previous studies in healthy
volunteers and patients.
The exposure in the planned clinical study (250 mg given as a single dose IV
injection), will be lower than in the medium dose group in the toxicity
studies, conservatively estimated to approximately 1/5 .
All patients will be carefully monitored to ensure that potential risks are
minimized. The risk/benefit balance using a single dose of ATH3G10 in patients
suffering a STEMI with ST elevation remaining despite PCI, is therefore
considered acceptable.
Sankt Eriksgatan 117, level 4
Stockholm 113 43
SE
Sankt Eriksgatan 117, level 4
Stockholm 113 43
SE
Listed location countries
Age
Inclusion criteria
Patients must fulfil all of the following criteria to be included in the study:
1. Provision of informed consent
2. Symptoms and signs consistent with acute MI and ST elevation at the J-point
in two contiguous leads (cut-points: >0.2mV in men and >0.15 mV in women in
leads V2-V3 and/or >0.1 mV in other leads)
3. Start of PCI, defined as when the guide wire is passed through the stenosis,
less than 4 hours after symptom onset
4. TIMI flow grade 0 at angiography before PCI in left anterior descending
coronary artery (segment 6 or 7) without collaterals OR TIMI flow grade less
than 3 in any infarct related main coronary arteries after PCI
5. Age 40-85, inclusive
--Females must be of non-childbearing potential at screening confirmed by
fulfilling one of the following criteria a) postmenopausal defined as
amenorrhea for at least 12 months, or b) documentation of irreversible surgical
sterilization.
Exclusion criteria
1. Cardiogenic chock, non-compensated acute heart failure and/or pulmonary
oedema.
2. Previous major vascular intervention within the last 4 weeks.
3. History of an infarct in the same artery that is currently affected.
4. Thrombolysis prior to admission.
5. Previous treatment with ATH3G10
6. Weight of less than 63 kg at screening (results in dose more than 4 mg/kg
body weight)7.
8. Recent (<1 month prior to screening) or current treatment with methotrexate
and/or tumour necrosis factor alpha (TNF*) inhibitors such as infliximab.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003676-12-NL |
| CCMO | NL70235.100.19 |