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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
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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 evaluate the effect of short-term i.v. administration of serelaxin in CHF patients on the geometric mean of hs-cTnI concentrations compared to placebo (both in addition to SoC) after an exercise testing session. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of short-term i.v. administration of serelaxin in CHF patients on the geometric mean of hs-cTnI concentrations compared to placebo at 4 and 5 hours after the start of an exercise testing session.
- To evaluate the effect of short-term i.v. administration of serelaxin in CHF patients on the geometric mean of N terminal pro-brain natriuretic peptide (NT-proBNP) concentrations after an exercise testing session.
- To evaluate the effect of short-term i.v. administration of serelaxin in CHF patients on the geometric mean of heart-type fatty acid-binding protein (H-FABP).
- To evaluate the safety and tolerability of i.v. serelaxin in CHF patients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provide written informed consent before any assessment is
performed.
2. Male or female ≥ 18 years of age, with body weight ≤ 160 Kg.
3. Diagnosis of stable CHF:
- New York Heart Association (NYHA) functional Class II and III.
- Receiving guideline-recommended treatment for CHF.
4. Left ventricular ejection fraction < 50%.
5. NT-proBNP > 250 ng/L in sinus rhythm or > 750 ng/L if not in sinus
rhythm (determined locally).
6. Ability to exercise for at least 10 to 12 minutes based on
investigator's judgment.
7. Systolic BP ≥ 125 mmHg at screening.
8. Renal function defined as an eGFR of ≥ 25 mL/min/1.73 m2 at |
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E.4 | Principal exclusion criteria |
1. Dyspnea primarily due to non-cardiac causes.
2. Worsening symptoms, e.g., fatigue, dyspnea, breathlessness within the 3 months prior to screening.
3. Increased risk of developing hypotension during vasodilator therapy according to investigators judgement.
4. Any contraindication for exercise testing and spirometry.
5. Stopping of the spirometry at screening according to the stopping rules, unless the patient has reached maximum exercise capacity defined as carbon dioxide production/oxygen consumption (VCO2/VO2) > 1.05.
6. Change in guideline-recommended CHF treatment within 1 month prior to screening.
7. Clinical evidence of acute coronary syndrome within 90 days prior to enrollment.
8. Significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate < 45 beats per minute or atrial fibrillation/flutter with sustained ventricular response of > 90 beats per minute at rest.
9.Severe renal impairment defined as eGFR < 25 mL/min/1.73m2 before randomization.
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E.5 End points |
E.5.1 | Primary end point(s) |
determine changes in plasma concentrations of hs cTnI following a cardiac stress test |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at 0, 132, 180, 240, 300, 360, 420 minutes |
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E.5.2 | Secondary end point(s) |
- Determine changes in plasma concentrations of hs cTnI, NT-proBNP and H-FABP following a cardiac stress test. (efficacy)
- ECG, Physical examination, vital signs, Laboratory evaluation, Clinical chemistry, Hematology (safety) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- efficacy: at 0, 132, 180, 240, 300, 360, 420 minutes
- safety: at screening and start of the infusion for both treatment period as well as at Day 29 (follow up period 15 days after treatment period 2) |
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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 | 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 | 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 | No |
E.8.1.6 | Cross over | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Germany |
Switzerland |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 14 |
E.8.9.2 | In all countries concerned by the trial days | 0 |