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

Chronic Heart Failure Clinical Trial

— RELAX-REPEAT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01982292
• Other study ID #: CRLX030A2209
• Secondary ID: 2013-002781-39
• Status: Completed
• Phase: Phase 2
• First received: November 6, 2013
• Last updated: February 23, 2016
• Start date: May 2014
• Est. completion date: September 2015

Study information

• Verified date: February 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety of repeat doses of serelaxin in chronic heart failure. At the same time, markers of efficacy will also be collected as exploratory measures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 321
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Other protocol defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• Serelaxin
A continuous 48 hour infusion of serelaxin administered every 4 weeks for a total of 3 doses.
• Placebo
A continuous 48 hour infusion of placebo administered every 4 weeks for a total of 3 doses.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Geelong	Victoria
Australia	Novartis Investigative Site	Melbourne
Czech Republic	Novartis Investigative Site	Brno - Bohunice
Czech Republic	Novartis Investigative Site	JIhlava
Czech Republic	Novartis Investigative Site	Praha 2
Finland	Novartis Investigative Site	Turku
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Grunstadt
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Luebeck
Germany	Novartis Investigative Site	Magdeburg
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Cortona	AR
Italy	Novartis Investigative Site	Monza	MB
Italy	Novartis Investigative Site	Vimercate	MI
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Sneek	The Netherlands
Norway	Novartis Investigative Site	Oslo
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Craiova
Romania	Novartis Investigative Site	Sibiu
Romania	Novartis Investigative Site	Targu Mures	Mures
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Villamartin	Cadiz
Sweden	Novartis Investigative Site	Stockholm
Turkey	Novartis Investigative Site	Diskapi / Ankara
Turkey	Novartis Investigative Site	Haydarpasa/Istanbul
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Meselik / Eskisehir
Turkey	Novartis Investigative Site	Sivas
United States	Novartis Investigative Site	Anaheim	California
United States	Novartis Investigative Site	Chapel Hill	North Carolina
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	South Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Czech Republic,  Finland,  Germany,  Italy,  Netherlands,  Norway,  Romania,  Russian Federation,  Spain,  Sweden,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		16 weeks	Yes
Secondary	Percentage of participants with chronic heart failure who develop anti-serelaxin antibodies after a single infusion (Week 4), two infusions (Week 8) or three infusions (Week 12) of serelaxin.		Week 4, Week 8, Week 12	Yes
Secondary	Antibody levels in subjects with chronic heart failure who develop 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	Yes
Secondary	Number of patients with adverse events	Incidence rate of adverse events, including serious adverse events, death, and overall, which occur during and after administration of repeated infusions of serelaxin relative to placebo in subjects with chronic heart failure will be reported.	16 weeks	Yes
Secondary	Pharmacokinetics of RLX030: Area under the plasma concentration time curve from time zero up to 48 hours post dose (AUC 0-48)	Characterization of the pharmacokinetics of serelaxin during and after drug administration of repeated infusions.	pre-infusion and 8, 24 and 48 hours post each infusion.	No
Secondary	Percentage of participants with chronic heart failure who develop neutralizing or non-neutralizing anti-serelaxin antibodies at any time following 3 repeated infusions and at Week 4, Week 8, and Week 12		12 weeks	Yes
Secondary	Pharmacokinetics of RLXL030: actual concentrations over time		pre-infusion and 8, 24, and 48 hours post each infusion	No
Secondary	Pharmacokinetics of RLX030: Cmax steady state (Cmaxss) concentration at 48 hours		48 hours post each infusion	No
Secondary	Pharmacokinetics of RLX030: clearance of serelaxin		48 hours after every infusion	No