Clinical trial NCT01982292: Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure
Official title: Prospective, Double-Blind, Multicenter Study Evaluating the Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Heart Failure
Keywords: Chronic Heart Failure, CHF, Heart Failure, HF, Immunogenicity, Anti-bodies, Hypersensitivity, Serelaxin, RELAX-REPEAT
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-11-13
Enrollment: 321
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 16 weeks
Secondary outcomes:
measure: 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
timeFrame: Randomization to Week 4, Week 4 to Week 8, Week 8 to Week 12, week 12 to week 16
measure: 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
timeFrame: Week 4, Week 8, Week 12
measure: 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)
timeFrame: At Week 4, Week 8, Week 12
measure: Number of Participants With Adverse Events Such as Adjudicated Potential Hypersensitivity or Infusion Reactions
timeFrame: 16 weeks
measure: Pharmacokinetics of RLX030: Area Under the Plasma Concentration Time Curve From Time Zero up to 48 Hours Post Dose (AUC 0-48)
timeFrame: pre-infusion and 8, 24 and 48 hours post each infusion.
measure: Pharmacokinetics of RLXL030: Actual Concentrations at Steady State (Css)
timeFrame: pre-infusion and 24, 48 hours post each infusion
measure: Pharmacokinetics of RLX030: Cmax Steady State (Cmaxss) Concentration at 48 Hours
timeFrame: 48 hours post each infusion
measure: Pharmacokinetics of RLX030: Clearance of Serelaxin (CL)
timeFrame: 48 hours post each infusion
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Novartis Investigative Site
state: California
city: Colorado Springs
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: South Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Richmond
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Geelong
country: Australia
facility: Novartis Investigative Site
city: Melbourne
country: Australia
facility: Novartis Investigative Site
city: Brno - Bohunice
country: Czech Republic
facility: Novartis Investigative Site
city: JIhlava
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 2
country: Czech Republic
facility: Novartis Investigative Site
city: Turku
country: Finland
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Greifswald
country: Germany
facility: Novartis Investigative Site
city: Grunstadt
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Luebeck
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Cortona
country: Italy
facility: Novartis Investigative Site
state: AR
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Vimercate
country: Italy
facility: Novartis Investigative Site
state: MI
city: Sneek
country: Netherlands
facility: Novartis Investigative Site
state: The Netherlands
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Targu Mures
country: Romania
facility: Novartis Investigative Site
state: Mures
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Craiova
country: Romania
facility: Novartis Investigative Site
city: Sibiu
country: Romania
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Villamartin
country: Spain
facility: Novartis Investigative Site
state: Cadiz
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Diskapi / Ankara
country: Turkey
facility: Novartis Investigative Site
city: Haydarpasa/Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Meselik / Eskisehir
country: Turkey
facility: Novartis Investigative Site
city: Sivas
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Kumar VA, Wilson SS, Ayaz SI, Levy PD. Targeted biological therapies reach the heart: the case of serelaxin for heart failure. Drugs Today (Barc). 2015 Oct;51(10):591-7. doi: 10.1358/dot.2015.51.10.2386731.