Chronic Heart FailurePhase 2RELAX-REPEATNCT01982292
Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure
A Phase 2 study testing RLX030 (serelaxin) in people with Chronic Heart Failure, run by Novartis Pharmaceuticals at 52 sites in 13 countries.
Trial summary
The purpose of this study was to assess the safety of repeat doses of serelaxin in chronic heart failure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Heart Failure
- What is being tested?
- RLX030 (serelaxin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 321 participants
- Where
- 52 sitesin 13 countries
- Study dates
- May 2014to Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
52 sites in 13 countries.
52 sites in 13 countries
Germany11 sites
Novartis Investigative Site
Berlin, State of Berlin, 10117
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Dresden, 01069
Novartis Investigative Site
Frankfurt, 60488
Novartis Investigative Site
Greifswald, 17475
Novartis Investigative Site
Grünstadt, D-67269
Novartis Investigative Site
Hanover, Lower Saxony, 30159
Novartis Investigative Site
Jena, 07740
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Lübeck, Germany, 23562
Novartis Investigative Site
Magdeburg, 39112
United States9 sites
Novartis Investigative Site
Anaheim, California, 92801
Novartis Investigative Site
Chapel Hill, North Carolina, 27599-7075
Novartis Investigative Site
Colorado Springs, Colorado, 80918
Novartis Investigative Site
Jacksonville, Florida, 32216
Novartis Investigative Site
Knoxville, Tennessee, 37920
Novartis Investigative Site
Minneapolis, Minnesota, 55404
Novartis Investigative Site
Minneapolis, Minnesota, 55417
Novartis Investigative Site
Richmond, Virginia, 23298-0050
Novartis Investigative Site
South Miami, Florida, 33143
Romania5 sites
Novartis Investigative Site
Bucharest, Romania, 014461
Novartis Investigative Site
Bucharest, 021659
Novartis Investigative Site
Craiova, 200642
Novartis Investigative Site
Sibiu, 550245
Novartis Investigative Site
Târgu Mureş, Mureș County, 540136
Spain5 sites
Novartis Investigative Site
Madrid, Madrid, 28007
Novartis Investigative Site
Madrid, Madrid, 28040
Novartis Investigative Site
Málaga, Andalusia, 29010
Novartis Investigative Site
Seville, Andalusia, 41014
Novartis Investigative Site
Villamartín, Cadiz, 11650
Turkey (Türkiye)5 sites
Novartis Investigative Site
Diskapi / Ankara, 06110
Novartis Investigative Site
Haydarpasa/Istanbul, 34668
Novartis Investigative Site
Kocaeli, 41380
Novartis Investigative Site
Meselik / Eskisehir, 26480
Novartis Investigative Site
Sivas, 58140
Italy4 sites
Novartis Investigative Site
Brescia, BS, 25123
Novartis Investigative Site
Cortona, AR, 52044
Novartis Investigative Site
Monza, MB, 20900
Novartis Investigative Site
Vimercate, MI, 200059
Czechia3 sites
Novartis Investigative Site
Brno-Bohunice, Czech Republic, 625 00
Novartis Investigative Site
Jihlava, 586 01
Novartis Investigative Site
Prague, 128 08
Netherlands3 sites
Novartis Investigative Site
Groningen
Novartis Investigative Site
Rotterdam, 3000 CA
Novartis Investigative Site
Sneek, The Netherlands, 8601 ZR
Australia2 sites
Novartis Investigative Site
Geelong, 3220
Novartis Investigative Site
Melbourne, VIC 3004
Russia2 sites
Novartis Investigative Site
Moscow, 109469
Novartis Investigative Site
Moscow, 117198
About this study
Official title: Prospective, Double-Blind, Multicenter Study Evaluating the Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure
The purpose of this study was to assess the safety of repeat doses of serelaxin in chronic heart failure.
- Conditions
- Chronic Heart Failure
- Being tested
- RLX030 (serelaxin), Placebo
- Keywords
- Chronic Heart Failure, CHF, Heart Failure, HF, Immunogenicity, Anti-bodies, Hypersensitivity, Serelaxin, RELAX-REPEAT
- Medical subject headings
- Heart Failure, Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RLX030 (serelaxin)Drug
Also called RLX030
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.
PlaceboDrug
Matching placebo of serelaxin was administered as a continuous IV infusion for 48 hours.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
Measured: 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)
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
Measured: At Week 4, Week 8, Week 12
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.
Measured: 16 weeks
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.
Measured: pre-infusion and 8, 24 and 48 hours post each infusion.
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
Measured: pre-infusion and 24, 48 hours post each infusion
Pharmacokinetics of RLX030: Cmax Steady State (Cmaxss) Concentration at 48 Hours
This analysis was not done due to sparse PK sampling.
Measured: 48 hours post each infusion
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.
Measured: 48 hours post each infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2013 (estimated)
- Study startMay 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Heart FailureStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 321 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01982292
- Sponsor's protocol ID
- CRLX030A2209
- Other IDs
- 2013-002781-39
- Acronym
- RELAX-REPEAT
- Status last verified
- Sep 2016
- First submitted
- 6 Nov 2013
- Last updated
- 9 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 26583301
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Double-Blind, Multicenter Study Evaluating the Safety of Repeat Doses of IV Serelaxin in Subjects With Chronic Heart Failure
- ClinicalTrials.gov ID
- NCT01982292
- Acronym / sponsor ID
- RELAX-REPEAT / CRLX030A2209
- Conditions
- Chronic Heart Failure
- Keywords
- Chronic Heart Failure, CHF, Heart Failure, HF, Immunogenicity, Anti-bodies, Hypersensitivity, Serelaxin, RELAX-REPEAT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 321 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 13 Nov 2013 (estimated)
- Results
- Posted 9 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to assess the safety of repeat doses of serelaxin in chronic heart failure.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RLX030 (serelaxin) | Experimental | Drug: 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 | Placebo comparator | Drug: PlaceboRandomized patients received an IV infusion of placebo of serelaxin for 48 hours at randomization and at Weeks 4 and 8 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RLX030 (serelaxin)Also: RLX030RLX030 (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. | Drug | RLX030 (serelaxin) |
| PlaceboMatching placebo of serelaxin was administered as a continuous IV infusion for 48 hours. | Drug | Placebo |
Primary outcome
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.
8 secondary outcomes
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
Time frame: 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
Time frame: 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)
Time frame: At Week 4, Week 8, Week 12
Number of Participants With Adverse Events Such as Adjudicated Potential Hypersensitivity or Infusion Reactions
Time frame: 16 weeks
Pharmacokinetics of RLX030: Area Under the Plasma Concentration Time Curve From Time Zero up to 48 Hours Post Dose (AUC 0-48)
Time frame: pre-infusion and 8, 24 and 48 hours post each infusion.
Pharmacokinetics of RLXL030: Actual Concentrations at Steady State (Css)
Time frame: pre-infusion and 24, 48 hours post each infusion
Pharmacokinetics of RLX030: Cmax Steady State (Cmaxss) Concentration at 48 Hours
Time frame: 48 hours post each infusion
Pharmacokinetics of RLX030: Clearance of Serelaxin (CL)
Time frame: 48 hours post each infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26583301Kumar 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
52 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RLX030 (serelaxin) in people with Chronic Heart Failure, run by Novartis Pharmaceuticals at 52 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 52 sites in Germany, United States, Romania, Spain, Turkey (Türkiye) and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01982292, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2016.