E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cardiac allograft vasculopathy in de-novo heart transplant recipients |
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E.1.1.1 | Medical condition in easily understood language |
Coronary artery disease in newly transplanted hearts |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 |
The main goal of this study is to evaluate the effect of evolocumab administered subcutaneously every month for one year on the development of cardiac allograft vasculopathy in cardiac allograft recipients. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess the impact of treatment on: i) cholesterol levels, ii) clinical events (death, myocardial infarction, percutaneous coronary intervention/coronary bypass surgery, cerebral stroke, cancer, end stage renal disease), iii) renal function, iv) inflammation, v) cardiac function as assessed by biomarkers and echocardiography, vi) quality of life, vii) the number of rejections, and (viii) safety and tolerability. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Heart transplant recipient within the last 4 – 8 weeks. • Age between 18 and 70 years. • Informed consent obtained and documented according to Good Clinical Practice (GCP), and national/regional regulations. • No contraindications to coronary angiography with intravascular ultrasound • Estimated glomerular filtration rate > 20 ml/min/1.73 m2 as assessed by the MDRD formula.
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E.4 | Principal exclusion criteria |
• Decompensated liver disease (Child-Pugh class C) • Severe renal failure, i.e. eGFR < 20 ml/min/1.73 m2 or on renal replacement therapy • Ongoing rejections or infections • Known sensitivity or intolerance to evolocumab or any of the excipients of Repatha® • Prior use of PCSK9 inhibition treatment • Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake • Participation in another clinical trial involving an investigational drug and/or follow-up within 30 days prior to enrolment. • Pregnancy. • Female subject who has either (1) not used at least one highly effective method of birth control for at least 1 month prior to screening or is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilised or postmenopausal
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the baseline-adjusted maximal intimal thickness as measured by coronary intravascular ultrasound (IVUS) at end-of treatment, 12 months after randomsation. The maximal intima thickness is defined as the largest distance (in mm) from the intimal leading edge to the external elastic membrane. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary end-point will be assessed at the end of treatment (after 12 months of treatment with the IMP). |
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E.5.2 | Secondary end point(s) |
• Percent atheroma volume as measured by IVUS • Cardiac allograft vasculopathy (defined as mean a maximal intimal thickness ≥0.5 mm over the entire matched segment) • LDL cholesterol • Index of Microvascular Resistance • Time to the first occurrence of a major clinical adverse event (death, myocardial infarction, percutaneous coronary intervention/coronary bypass surgery, cerebral stroke, cancer, end stage renal disease) • Estimated GFR • Quality of life as assessed by the SF-36 and 5D EuroQoL questionnaires • N-terminal pro-B-type natriuretic peptide (NT-proBNP) • Cardiac troponin T (TnT) • C-reactive protein (CRP) • The number of rejections • The number of adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints will be assessed at the end of treatment (after 12 months of treatment with the IMP). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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
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End of trial: Last patient, last visit |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |