E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
assess the safety of repeat doses of serelaxin in chronic heart failure |
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E.2.2 | Secondary objectives of the trial |
- assess the incidence rate of adverse events of special interest, indicative of hypersensitivity reactions
- assess the safety and tolerability of repeated infusions of serelaxin relative to placebo, in subjects with chronic heart failure
-characterize the pharmacokinetics of serelaxin during and after administration of repeated infusions |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Body weight of ≤ 160 kg
- Subjects with compensated CHF (NYHA Class II – III) at time of screening with a prior documented history of chronic heart failure
- NT-proBNP >300 pg/ml (according to central measurement) at visit 1
- Subjects treated with appropriate and guideline-indicated CHF standard of care
- Ability to comply with all requirements, including ability to receive at least a 48 hour infusion plus follow-up time required for each dosing visit. |
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E.4 | Principal exclusion criteria |
- Current acute decompensated HF
- Any major solid organ transplant recipient or planned anticipated organ transplant within 1 year
- Documented history of untreated ventricular arrhythmia with syncopal episodes, ventricular tachycardia, or ventricular fibrillation without ICD (implantable cardioverter defibrillator) with significant
hemodynamic consequences within the 3 months prior to screening
- Presence of hemodynamically significant mitral and /or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation: including significant left ventricular outflow obstruction (e.g., obstructive hypertrophic cardiomyopathy, severe aortic stenosis)
- Subjects with severe renal impairment defined as prerandomization eGFR < 30 ml/min/1.73m2 calculated using the sMDRD equation and/or those receiving current or planned dialysis or ultrafiltration |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of participants with chronic heart failure who develop anti-serelaxin antibodies following repeat administration of IV continuous infusions of serelaxin up to 48 hours |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Percentage of participants with chronic heart failure who develop anti-serelaxin antibodies
- Antibody levels in subjects with chronic heart failure who develop anti-serelaxin antibodies (neutralizing, non-neutralizing or both)
- Number of patients with adverse events
- Percentage of participants with chronic heart failure who develop anti-serelaxin antibodies neutralizing or non-neutralizing
- Pharmacokinetics of RLX030: Area under the plasma concentration time curve from time zero up to 48 hours post dose (AUC 0-48), actual
concentrations over time,
- Pharmacokinetics of RLX030: Cmax steady state (Cmaxss) concentration, clearance of serelaxin
|
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- after a single infusion (Week 4), two infusions (Week 8) or three infusions (Week 12) of serelaxin.
- at any time following 3 repeated infusions and at Week 4, Week 8 and Week 12.
- 16 Weeks
- at any time following 3 repeated infusions and at Week 4, Week 8 and Week 12.
- pre-infusion and 8, 24 and 48 hours post each infusion.
- 48 hours after every infusion |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Italy |
Norway |
Romania |
Sweden |
Australia |
Finland |
Germany |
Spain |
Russian Federation |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |