Prospective, Double-Blind, Multicenter Study Evaluating the Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 321
- Locations
- 1
- Primary Endpoint
- 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
Study Overview
Brief Summary
The purpose of this study was to assess the safety of repeat doses of serelaxin in chronic heart failure.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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 pre-randomization eGFR < 30 ml/min/1.73m2 calculated using the sMDRD equation and/or those receiving current or planned dialysis or ultrafiltration
Arms & Interventions
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
Intervention: RLX030 (serelaxin) (Drug)
Placebo
Randomized patients received an IV infusion of placebo of serelaxin for 48 hours at randomization and at Weeks 4 and 8
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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
- 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(Week 4, Week 8, Week 12)
- Pharmacokinetics of RLXL030: Actual Concentrations at Steady State (Css)(pre-infusion and 24, 48 hours post each infusion)
- Pharmacokinetics of RLX030: Clearance of Serelaxin (CL)(48 hours post each infusion)
- 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(Randomization to Week 4, Week 4 to Week 8, Week 8 to Week 12, week 12 to week 16)
- 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)(At Week 4, Week 8, Week 12)
- Number of Participants With Adverse Events Such as Adjudicated Potential Hypersensitivity or Infusion Reactions(16 weeks)
- Pharmacokinetics of RLX030: Area Under the Plasma Concentration Time Curve From Time Zero up to 48 Hours Post Dose (AUC 0-48)(pre-infusion and 8, 24 and 48 hours post each infusion.)
- Pharmacokinetics of RLX030: Cmax Steady State (Cmaxss) Concentration at 48 Hours(48 hours post each infusion)