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

NCT01982292 | Completed Phase 2 Results

• 2 other identifiers: CRLX030A22092013-002781-39
• Study Type: interventional
• Target: 321
• Locations: 13 countries
• Sites: 52

Brief Summary

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

Conditions

Chronic Heart Failure

Keywords

Chronic Heart Failure, CHF, Heart Failure, HF, Immunogenicity, Anti-bodies, Hypersensitivity, Serelaxin, RELAX-REPEAT

Outcome Measures

Primary Outcomes (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

  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.

  16 weeks

Secondary Outcomes (8)

• 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

• 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

• 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.

Study Arms (2)

RLX030 (serelaxin)

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

RLX030 (serelaxin) DRUG

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.

Also known as: RLX030

RLX030 (serelaxin)

Placebo DRUG

Matching placebo of serelaxin was administered as a continuous IV infusion for 48 hours.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (52)

Novartis Investigative Site

Anaheim, California, 92801, United States

Location

Novartis Investigative Site

Colorado Springs, Colorado, 80918, United States

Location

Novartis Investigative Site

Jacksonville, Florida, 32216, United States

Location

Novartis Investigative Site

South Miami, Florida, 33143, United States

Location

Novartis Investigative Site

Minneapolis, Minnesota, 55404, United States

Location

Novartis Investigative Site

Minneapolis, Minnesota, 55417, United States

Location

Novartis Investigative Site

Chapel Hill, North Carolina, 27599-7075, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37920, United States

Location

Novartis Investigative Site

Richmond, Virginia, 23298-0050, United States

Location

Novartis Investigative Site

Geelong, 3220, Australia

Location

Novartis Investigative Site

Melbourne, VIC 3004, Australia

Location

Novartis Investigative Site

Brno-Bohunice, Czech Republic, 625 00, Czechia

Location

Novartis Investigative Site

Jihlava, 586 01, Czechia

Location

Novartis Investigative Site

Prague, 128 08, Czechia

Location

Novartis Investigative Site

Turku, Finland, 20521, Finland

Location

Novartis Investigative Site

Lübeck, Germany, 23562, Germany

Location

Novartis Investigative Site

Hanover, Lower Saxony, 30159, Germany

Location

Novartis Investigative Site

Berlin, State of Berlin, 10117, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Dresden, 01069, Germany

Location

Novartis Investigative Site

Frankfurt, 60488, Germany

Location

Novartis Investigative Site

Greifswald, 17475, Germany

Location

Novartis Investigative Site

Grünstadt, D-67269, Germany

Location

Novartis Investigative Site

Jena, 07740, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Magdeburg, 39112, Germany

Location

Novartis Investigative Site

Cortona, AR, 52044, Italy

Location

Novartis Investigative Site

Brescia, BS, 25123, Italy

Location

Novartis Investigative Site

Monza, MB, 20900, Italy

Location

Novartis Investigative Site

Vimercate, MI, 200059, Italy

Location

Novartis Investigative Site

Sneek, The Netherlands, 8601 ZR, Netherlands

Location

Novartis Investigative Site

Groningen, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3000 CA, Netherlands

Location

Novartis Investigative Site

Oslo, 0424, Norway

Location

Novartis Investigative Site

Târgu Mureş, Mureș County, 540136, Romania

Location

Novartis Investigative Site

Bucharest, Romania, 014461, Romania

Location

Novartis Investigative Site

Bucharest, 021659, Romania

Location

Novartis Investigative Site

Craiova, 200642, Romania

Location

Novartis Investigative Site

Sibiu, 550245, Romania

Location

Novartis Investigative Site

Moscow, 109469, Russia

Location

Novartis Investigative Site

Moscow, 117198, Russia

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Seville, Andalusia, 41014, Spain

Location

Novartis Investigative Site

Villamartín, Cadiz, 11650, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28007, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28040, Spain

Location

Novartis Investigative Site

Stockholm, 141 86, Sweden

Location

Novartis Investigative Site

Diskapi / Ankara, 06110, Turkey (Türkiye)

Location

Novartis Investigative Site

Haydarpasa/Istanbul, 34668, Turkey (Türkiye)

Location

Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

Location

Novartis Investigative Site

Meselik / Eskisehir, 26480, Turkey (Türkiye)

Location

Novartis Investigative Site

Sivas, 58140, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 26583301 DERIVED

MeSH Terms

Conditions

Heart Failure; Hypersensitivity

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2013
• First Posted: November 13, 2013
• Study Start: May 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: November 9, 2016
• Results First Posted: November 9, 2016

Record last verified: 2016-09

Locations

NO (1); RO (5); AU (2); ES (5); FI (1); NL (3); RU (2); IT (4); TU (5); CZ (3); DE (11); SE (1); US (9)