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Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure (RELAX-REPEAT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01982292
Recruitment Status : Completed
First Posted : November 13, 2013
Results First Posted : November 9, 2016
Last Update Posted : November 9, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Chronic Heart Failure Drug: RLX030 (serelaxin) Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 321 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Official Title: Prospective, Double-Blind, Multicenter Study Evaluating the Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure
Study Start Date : May 2014
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: RLX030 (serelaxin)
Randomized patients received an IV infusion of 30 μg/kg/day of serelaxin for 48 hours at randomization and at Weeks 4 and 8
Drug: RLX030 (serelaxin)
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 Name: RLX030

Placebo Comparator: Placebo
Randomized patients received an IV infusion of placebo of serelaxin for 48 hours at randomization and at Weeks 4 and 8
Drug: Placebo
Matching placebo of serelaxin was administered as a continuous IV infusion for 48 hours.




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01982292


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01982292    
Other Study ID Numbers: CRLX030A2209
2013-002781-39 ( EudraCT Number )
First Posted: November 13, 2013    Key Record Dates
Results First Posted: November 9, 2016
Last Update Posted: November 9, 2016
Last Verified: September 2016
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Chronic Heart Failure, CHF, Heart Failure, HF, Immunogenicity, Anti-bodies, Hypersensitivity, Serelaxin, RELAX-REPEAT
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases