Primary:Assess the safety of repeat doses of serelaxin in chronic heart failureSecondary:- Assess the incidence rate of adverse events of special interest, indicative of hypersensitivity reactions- Assess the safety and tolerability of repeated…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage of participants with chronic heart failure who develop antiserelaxin
antibodies following repeat administration of IV continuous
infusions of serelaxin up to 48 hours
Secondary outcome
- Percentage of participants with chronic heart failure who develop
antiserelaxin antibodies
- Antibody levels in subjects with chronic heart failure who develop
antiserelaxin antibodies (neutralizing, non-neutralizing or both)
- Number of patients with adverse events
- Percentage of participants with chronic heart failure who develop
antiserelaxin 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
Background summary
The purpose and rationale of this study is to evaluate the safety of repeat 48
hour IV serelaxin (RLX030A) dosing through the detection of anti-serelaxin
antibodies and any related adverse events. Data from this study will be
collected from a stable CHF subject population and used to support registration
of serelaxin as a treatment to improve outcomes in subjects with acute heart
failure.
Study objective
Primary:
Assess the safety of repeat doses of serelaxin in chronic heart failure
Secondary:
- 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
Study design
This is a multicenter, randomized, double-blind, parallel group,
placebo-controlled, 2-arm trial to evaluate the safety of repeated serelaxin
exposure in subjects with stable, chronic heart failure (CHF NYHA Class II *
III )
Intervention
IV infusion with serelaxin/placebo for 48 hours; 3x.
Study burden and risks
Burden and risks of participation is the chance of side effects from the study
medication and inconveniences of blood sampling and the infusion.
The known side effects of the study medication include reducing blood pressure,
anemia and menstrual disorders (longer, heavier, irregular / more frequent
bleeding). Reduction of blood pressure and anemia can cause symptoms such as
dizziness or fainting. Reduction of potassium in the blood is also observed
during treatment with serelaxin. A decrease of potassium in the blood can lead
to symptoms such as muscle weakness, muscle cramps, and a disturbed heart
rhythm.
In addition, antibodies are observed after treatment with serelaxin. Up to now,
no adverse effects of antibodies seen. Serelaxin is a protein. That means there
is a risk of severe allergic reactions. These are allergic reactions such as a
greatly reduced blood pressure and respiratory problems.
Risks and discomforts are expected to be minor and acceptable.
3x IV infusion requiring hospitalization for 53 hours. At least 6 visits and
more frequent blood sampling, measurement of weight, respiratory rate, blood
pressure, pulse and body temperature and performing physical examination than
standard. Total duration is estimated at a minimum of 172 hours.
There is no standard therapy denies.
There is no therapeutic effect is expected during this study, however, this
study may provide useful information for the future.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
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.
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
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 | EUCTR2013-002781-39-NL |
| ClinicalTrials.gov | NCT01982292 |
| CCMO | NL49578.042.14 |