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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01982292




Registration number
NCT01982292
Ethics application status
Date submitted
6/11/2013
Date registered
13/11/2013
Date last updated
9/11/2016

Titles & IDs
Public title
Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure
Scientific title
Prospective, Double-Blind, Multicenter Study Evaluating the Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure
Secondary ID [1] 0 0
2013-002781-39
Secondary ID [2] 0 0
CRLX030A2209
Universal Trial Number (UTN)
Trial acronym
RELAX-REPEAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Heart Failure 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RLX030 (serelaxin)
Treatment: Drugs - Placebo

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

Placebo Comparator: Placebo - Randomized patients received an IV infusion of placebo of serelaxin for 48 hours at randomization and at Weeks 4 and 8


Treatment: Drugs: 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.

Treatment: Drugs: Placebo
Matching placebo of serelaxin was administered as a continuous IV infusion for 48 hours.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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 - 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.
Timepoint [1] 0 0
16 weeks
Secondary outcome [1] 0 0
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 - 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.
Timepoint [1] 0 0
Randomization to Week 4, Week 4 to Week 8, Week 8 to Week 12, week 12 to week 16
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Week 4, Week 8, Week 12
Secondary outcome [3] 0 0
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) - 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
Timepoint [3] 0 0
At Week 4, Week 8, Week 12
Secondary outcome [4] 0 0
Number of Participants With Adverse Events Such as Adjudicated Potential Hypersensitivity or Infusion Reactions - 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.
Timepoint [4] 0 0
16 weeks
Secondary outcome [5] 0 0
Pharmacokinetics of RLX030: Area Under the Plasma Concentration Time Curve From Time Zero up to 48 Hours Post Dose (AUC 0-48) - Due to sparse PK sampling, AUC 0-48 hours was not analyzed.
Timepoint [5] 0 0
pre-infusion and 8, 24 and 48 hours post each infusion.
Secondary outcome [6] 0 0
Pharmacokinetics of RLXL030: Actual Concentrations at Steady State (Css) - 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
Timepoint [6] 0 0
pre-infusion and 24, 48 hours post each infusion
Secondary outcome [7] 0 0
Pharmacokinetics of RLX030: Cmax Steady State (Cmaxss) Concentration at 48 Hours - This analysis was not done due to sparse PK sampling.
Timepoint [7] 0 0
48 hours post each infusion
Secondary outcome [8] 0 0
Pharmacokinetics of RLX030: Clearance of Serelaxin (CL) - 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.
Timepoint [8] 0 0
48 hours post each infusion

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Novartis Investigative Site - Geelong
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
3220 - Geelong
Recruitment postcode(s) [2] 0 0
VIC 3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Brno - Bohunice
Country [9] 0 0
Czech Republic
State/province [9] 0 0
JIhlava
Country [10] 0 0
Czech Republic
State/province [10] 0 0
Praha 2
Country [11] 0 0
Finland
State/province [11] 0 0
Turku
Country [12] 0 0
Germany
State/province [12] 0 0
Niedersachsen
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Dresden
Country [15] 0 0
Germany
State/province [15] 0 0
Frankfurt
Country [16] 0 0
Germany
State/province [16] 0 0
Greifswald
Country [17] 0 0
Germany
State/province [17] 0 0
Grunstadt
Country [18] 0 0
Germany
State/province [18] 0 0
Jena
Country [19] 0 0
Germany
State/province [19] 0 0
Kiel
Country [20] 0 0
Germany
State/province [20] 0 0
Luebeck
Country [21] 0 0
Germany
State/province [21] 0 0
Magdeburg
Country [22] 0 0
Italy
State/province [22] 0 0
AR
Country [23] 0 0
Italy
State/province [23] 0 0
BS
Country [24] 0 0
Italy
State/province [24] 0 0
MB
Country [25] 0 0
Italy
State/province [25] 0 0
MI
Country [26] 0 0
Netherlands
State/province [26] 0 0
The Netherlands
Country [27] 0 0
Netherlands
State/province [27] 0 0
Groningen
Country [28] 0 0
Netherlands
State/province [28] 0 0
Rotterdam
Country [29] 0 0
Norway
State/province [29] 0 0
Oslo
Country [30] 0 0
Romania
State/province [30] 0 0
Mures
Country [31] 0 0
Romania
State/province [31] 0 0
Bucharest
Country [32] 0 0
Romania
State/province [32] 0 0
Bucuresti
Country [33] 0 0
Romania
State/province [33] 0 0
Craiova
Country [34] 0 0
Romania
State/province [34] 0 0
Sibiu
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Moscow
Country [36] 0 0
Spain
State/province [36] 0 0
Andalucia
Country [37] 0 0
Spain
State/province [37] 0 0
Cadiz
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Sweden
State/province [39] 0 0
Stockholm
Country [40] 0 0
Turkey
State/province [40] 0 0
Diskapi / Ankara
Country [41] 0 0
Turkey
State/province [41] 0 0
Haydarpasa/Istanbul
Country [42] 0 0
Turkey
State/province [42] 0 0
Kocaeli
Country [43] 0 0
Turkey
State/province [43] 0 0
Meselik / Eskisehir
Country [44] 0 0
Turkey
State/province [44] 0 0
Sivas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study was to assess the safety of repeat doses of serelaxin in chronic
heart failure.
Trial website
https://clinicaltrials.gov/show/NCT01982292
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications