E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anterior STEMI revascularised by PPCI |
|
E.1.1.1 | Medical condition in easily understood language |
Acute heart attacks treated with a stent |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066641 |
E.1.2 | Term | Acute myocardial infarction, of anterior wall |
E.1.2 | System Organ Class | 100000004849 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the lowest dose of rituximab with the highest biological efficacy (B cell depletion) and the best safety profile (lowest incidence of undesirable effects) in patients with acute anterior myocardial infraction treated by PPCI. |
|
E.2.2 | Secondary objectives of the trial |
To determine the infarct size by serial cardiac biomarker release. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18-75 years old 2. Acute anterior STEMI and successful primary percutaneous coronary intervention (PCI) with stent inplantation in the culpirt lesion during the first 24hrs after onset of symptoms 3. Provision of written informed consent |
|
E.4 | Principal exclusion criteria |
1. Previous history of STEMI 2. Cardiogenic shock (systolic blood pressure <80mmHg; unresponsive to fluids, or necessitating catecholamines) electrical instability or severe congestive heart failure 3. corrected QT interval >500msecs using Bazett's formula 4. Hematologic abnormalities (hemoglobin <10g/dL or hematocrit <30%, platelet cell count of <100x10(3)/uL, white blood cell count <4x10(3)/uL) 5. Renal failure (estimated GFR by the MDRD formula <45ml/min/1.73m2) 6. Known hepatic failure or abnormal liver function tests at baseline (ALT>2xULN) 7. Active or recurrent hepatitis (type B) 8. Known HIV infection 9. Current or previous tuberculosis (CXR) 10. Current infections 11. Presence or history in the previous five years of an ongoing cancer, except in situe cancer of the cervix or basal cell carcinoma 12. Any oral or intravenous immunosuppressive treatment (other than concomitant 100mg methylprednisolone), disease modifying drugs or other immue modulatory monoclonal antibodies 13. Allergy to rituximab or one of its excipients 14. Expected need for vaccination with a live attenuated vaccine during the study including incomplete vaccination courses 15. Known or suspected preganacy at screening or lactating women 16. Women of childbearing age unless confirmed by direct questioning that they are reproductively sterile or post menopausal 17. Participation in other clinical trials 18. Inability to comply with study procedures |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To assess the safety of rituximab in ST-elevation myocardial infarction (STEMI) patients by monitoring their response to the drug in a controlled environment and on extended follow up. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary outcome measures will be assessed at days 1-6, day 14, day 30 and 6 months post infusion via: • Review of Adverse Events and Serious Adverse Events • Clinically significant changes in biochemical and haematological markers (serum creatinine, eGFR, liver function tests, blood glucose, full blood count and differential) • Clinically significant ECG changes (arrhythmias, ischaemic changes, QTc)
|
|
E.5.2 | Secondary end point(s) |
To assess the effect of rituximab on circulating B cells immediately after administration and on extended follow up. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endopoints i.e. kinetics and extent of reduction of B lymphocyte number in blood post infusion of Rituximab will be assessed at 30 mins, 6 hours, days 6, 14 and 6 months post infusion. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of trial is defined completion of the last follow-up visit of the last participant. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |