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Completed

NCT Number: NCT01982292

Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure

The purpose of this study was to assess the safety of repeat doses of serelaxin in chronic heart failure.

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Key information

Conditions

Chronic Heart Failure Cardiovascular Diseases Heart Diseases Heart Failure Hypersensitivity Immune System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Geelong, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key 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.

Key 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 pre-randomization eGFR < 30 ml/min/1.73m2 calculated using the sMDRD equation and/or those receiving current or planned dialysis or ultrafiltration

Treatment and study plan

RLX030 (serelaxin)

Drug

RLX030 (serelaxin) was administered according to a weight-range adjusted dosing regimen at a nominal dose of 30 μg/kg/day as a continuous IV infusion for 48 hours.

Other names: RLX030

Placebo

Drug

Matching placebo of serelaxin was administered as a continuous IV infusion for 48 hours.

Primary outcomes

  1. Percentage of Participants With Chronic Heart Failure (CHF) Who Develop Anti-serelaxin Antibodies at Any Time Following Repeat Administration of IV Continuous Infusions of Serelaxin Administered for up to 48 Hours in 16 Weeks

    Time frame: 16 weeks

    A patient is considered antibody positive during the study if he/she had at least two infusions and had at least one evaluable measurement to test for anti-serelaxin antibodies after each infusion and all evaluable antibody test results were positive.

    A patient is considered antibody negative during the study if he/she had at least two infusions and had at least one evaluable measurement to test for anti-serelaxin antibodies after each infusion and all evaluable antibody test results were negative. A patient's antibody status is considered to be undetermined during the study if it is not defined as positive or negative.

Secondary outcomes

  1. Percentage of Participants With Chronic Heart Failure Who Develop Positive Anti-serelaxin Antibodies After a Single Infusion of Serelaxin Over Time up to Week 16

    Time frame: Randomization to Week 4, Week 4 to Week 8, Week 8 to Week 12, week 12 to week 16

    A patient is considered antibody positive during the study if he/she had at least two infusions and had at least one evaluable measurement to test for anti-serelaxin antibodies after each infusion and all evaluable antibody test results were positive. Each time period is defined as the time frame from study drug initiation (or the visit if there is no infusion) to prior to study drug initiation of the next period (or the visit if no there is no infusion). n= The total number of subjects with evaluable antibody status during the defined period.

  2. Antibody Titers in Participants With Chronic Heart Failure Who Develop Positive Anti-serelaxin Antibodies (Neutralizing, Non-neutralizing or Both) at Any Time Following 3 Repeated Infusions and at Week 4, Week 8 and Week 12

    Time frame: Week 4, Week 8, Week 12

  3. Percentage of Participants With Chronic Heart Failure With Positive Antibody Status Who Develop Non-neutralizing Anti-serelaxin Antibodies Following 3 Repeated Infusions (i.e. at Week 4, Week 8, and Week 12)

    Time frame: At Week 4, Week 8, Week 12

    A patient is considered antibody positive during the study if he/she had at least two infusions and had at least one evaluable measurement to test for anti-serelaxin antibodies after each infusion and all evaluable antibody test results were positive.

    n = the total number of subjects with evaluable antibody status after specified number of infusions

  4. Number of Participants With Adverse Events Such as Adjudicated Potential Hypersensitivity or Infusion Reactions

    Time frame: 16 weeks

    Incidence rate of special interest, indicative of hypersensitivity reactions which occur during and after administration of repeated infusions of serelaxin relative to placebo in subjects with chronic heart failure is reported. Hypersensitivity reactions or infusion reactions can be headache, nausea, fever, chills, dizziness, flush, pruritus, chest and/or back pain.

  5. Pharmacokinetics of RLX030: Area Under the Plasma Concentration Time Curve From Time Zero up to 48 Hours Post Dose (AUC 0-48)

    Time frame: pre-infusion and 8, 24 and 48 hours post each infusion.

    Due to sparse PK sampling, AUC 0-48 hours was not analyzed.

  6. Pharmacokinetics of RLXL030: Actual Concentrations at Steady State (Css)

    Time frame: pre-infusion and 24, 48 hours post each infusion

    Concentration at steady state (Css) was estimated using C48 or C24 for patients who received the intended rate of infusion for at least 24hours. n: Number of patients with valid PK parameters available

  7. Pharmacokinetics of RLX030: Cmax Steady State (Cmaxss) Concentration at 48 Hours

    Time frame: 48 hours post each infusion

    This analysis was not done due to sparse PK sampling.

  8. Pharmacokinetics of RLX030: Clearance of Serelaxin (CL)

    Time frame: 48 hours post each infusion

    Clearance (CL) was calculated using concentration at steady state (Css) and the actual delivered dose rate. n: Number of patients with valid PK parameters available within 48 hours post each infusion.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

Prospective, Double-Blind, Multicenter Study Evaluating the Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure

Acronym: RELAX-REPEAT

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Nov 13, 2013
Registry last updated
Nov 9, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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