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Clinical Trial Results:
Multicenter, open-label, dose escalation study to evaluate safety, tolerability and pharmacokinetics of RLX030 in addition to standard of care in pediatric patients from birth to <18 years of age, hospitalized with acute heart failure

Summary
EudraCT number	2013-002847-28
Trial protocol	DE
Global end of trial date	03 Apr 2017

Results information
Results version number	v1(current)
This version publication date	14 Oct 2017
First version publication date	14 Oct 2017
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CRLX030A2208

ISRCTN number

US NCT number

NCT02151383

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001168-PIP01-11

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 Apr 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Apr 2017

Was the trial ended prematurely?

Yes

Main objective of the trial

-To evaluate the safety and tolerability of an iv serelaxin infusion in addition to standard of care in hospitalized pediatric patients with AHF -To investigate the effects of age on the pharmacokinetics of serelaxin given as iv infusion in addition to standard of care in hospitalized pediatric patients with AHF

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial. The investigator could prescribe any medications and/or supportive care during the study based on clinical needs.

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Sep 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

United Kingdom: 1

Country: Number of subjects enrolled

United States: 7

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 18 patients were assigned to study treatment. 6 patients were identified with GCP violations; hence, only 12 patients were included in disposition.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Serelaxin: Cohort 1

Arm description

Serelaxin was administered intravenously on top of standard therapy for acute heart failure, for a total of 48 hours. In Cohort 1, patients in age group of 6 to <18 years were enrolled either into a low-dose or a high-dose group. During this 48-hour treatment period, the serelaxin dose rates to be administered were 3 μg/kg/day, 10 μg/kg/day and 30 μg/kg/day in the low -dose group; 10 μg/kg/day, 30 μg/kg/day and 100 μg/kg/day in the high-dose group. Both the low-dose and high- dose groups were planned to receive equal number of patients.

Arm type

Experimental

Investigational medicinal product name

Serelaxin

Investigational medicinal product code

RLX030

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

The study drug was provided as a 1 mg/mL solution in 6 mL vials (with 3.5 mL fill). The required dose (μg/kg) was calculated for each patient at the assigned dose titration level.

Serelaxin: Cohort 2

Arm description

Serelaxin was administered intravenously on top of standard therapy for acute heart failure, for a total of 48 hours. In Cohort 2, patients in age group of 1 to <6 years were enrolled either into a low-dose or a high-dose group. During this 48-hour treatment period, the serelaxin dose rates to be administered were 3 μg/kg/day, 10 μg/kg/day and 30 μg/kg/day in the low -dose group; 10 μg/kg/day, 30 μg/kg/day and 100 μg/kg/day in the high-dose group. Both the low-dose and high- dose groups were planned to receive equal number of patients.

Arm type

Experimental

Investigational medicinal product name

Serelaxin

Investigational medicinal product code

RLX030

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

The study drug was provided as a 1 mg/mL solution in 6 mL vials (with 3.5 mL fill). The required dose (μg/kg) was calculated for each patient at the assigned dose titration level.

Serelaxin: Cohort 3

Arm description

Serelaxin was administered intravenously on top of standard therapy for acute heart failure, for a total of 48 hours. In Cohort 3, patients in age group of 1 month to <1 year were enrolled either into a low-dose or a high-dose group. During this 48-hour treatment period, the serelaxin dose rates to be administered were 3 μg/kg/day, 10 μg/kg/day and 30 μg/kg/day in the low -dose group; 10 μg/kg/day, 30 μg/kg/day and 100 μg/kg/day in the high-dose group. In this cohort, high- dose group was planned to receive twice the number of patients in low-dose group.

Arm type

Experimental

Investigational medicinal product name

Serelaxin

Investigational medicinal product code

RLX030

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

The study drug was provided as a 1 mg/mL solution in 6 mL vials (with 3.5 mL fill). The required dose (μg/kg) was calculated for each patient at the assigned dose titration level.

Number of subjects in period 1	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Started	8	3	1
Low-dose	2 ^[1]	3	1
High-dose	6 ^[2]	0 ^[3]	0 ^[4]
Completed	8	3	1

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: These are fix dose titration groups for the cohort where the cohort patients are assigned to either of these 2 groups.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: These are fix dose titration groups for the cohort where the cohort patients are assigned to either of these 2 groups.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: These are fix dose titration groups for the cohort where the cohort patients are assigned to either of these 2 groups.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: These are fix dose titration groups for the cohort where the cohort patients are assigned to either of these 2 groups.

Baseline characteristics

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Reporting group title

Overall Study

Reporting group description

These 12 patients are in enrolled and safety set which exclude the 6 patients identified with GCP violations

Reporting group values	Overall Study	Total
Number of subjects	12	12
Age categorical
Units: Subjects
Infants and toddlers (28 days-23 months)	2	2
Children (2-11 years)	5	5
Adolescents (12-17 years)	5	5
Age Continuous
Units: Years
arithmetic mean (standard deviation)	8.1 ( 5.17 )	-
Gender, Male/Female
Units: Subjects
Female	1	1
Male	11	11
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	2	2
Not Hispanic or Latino	7	7
Unknown or Not Reported	3	3

End points

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Reporting group title

Serelaxin: Cohort 1

Reporting group description

Reporting group title

Serelaxin: Cohort 2

Reporting group description

Reporting group title

Serelaxin: Cohort 3

Reporting group description

Primary: Number of patients reported with treatment emergent any adverse events, serious adverse events and death

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End point title

Number of patients reported with treatment emergent any adverse events, serious adverse events and death ^[1]

End point description

Number of patients with treatment emergent adverse events (including confirmed systolic blood pressure decreases and worsening heart failure), serious adverse events and death is reported.

End point type

Primary

End point timeframe

through 28 days + 30 days SAE follow up after completion or discontinuation from the study

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical hypothesis was planned to be tested.

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	8	3	1
Units: Patients
at least one Adverse Event	6	3	0
Serious Adverse Event	3	1	0
Death	0	0	0

No statistical analyses for this end point

Primary: Pharmacokinetic parameter: Css (steady state concentration)

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End point title

Pharmacokinetic parameter: Css (steady state concentration) ^[2]

End point description

Steady state concentration was planned to be estimated by 16 hour, 32 hour and 48 hour concentration for each dose level.

End point type

Primary

End point timeframe

at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical hypothesis was planned to be tested.

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	0 ^[3]	0 ^[4]	0 ^[5]
Units: ng/mL
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[3] - PK data was considered too limited for a meaningful interpretation
[4] - PK data was considered too limited for a meaningful interpretation
[5] - PK data was considered too limited for a meaningful interpretation

No statistical analyses for this end point

Primary: Pharmacokinetic parameter: CL (clearance)

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End point title

Pharmacokinetic parameter: CL (clearance) ^[6]

End point description

Clearance(CL) was planned to be estimated using steady state concentration (Css) and rate of infusion.

End point type

Primary

End point timeframe

at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical hypothesis was planned to be tested.

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	0 ^[7]	0 ^[8]	0 ^[9]
Units: mL/hr
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[7] - PK data was considered too limited for a meaningful interpretation
[8] - PK data was considered too limited for a meaningful interpretation
[9] - PK data was considered too limited for a meaningful interpretation

No statistical analyses for this end point

Secondary: Change from baseline of arterial blood pressure

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End point title

Change from baseline of arterial blood pressure

End point description

End point type

Secondary

End point timeframe

baseline, prior to each dose escalation, and at 24 hr. post end of infusion

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	0 ^[10]	0 ^[11]	0 ^[12]
Units: mmHg
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[10] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[11] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[12] - Data analysis was not done as limited set of data would preclude meaningful interpretation

No statistical analyses for this end point

Secondary: Change from baseline of central venous pressure (CVP)

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End point title

Change from baseline of central venous pressure (CVP)

End point description

End point type

Secondary

End point timeframe

baseline, prior to each dose escalation, and at 24 hr. post end of infusion

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	0 ^[13]	0 ^[14]	0 ^[15]
Units: mmHg
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[13] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[14] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[15] - Data analysis was not done as limited set of data would preclude meaningful interpretation

No statistical analyses for this end point

Secondary: Change from baseline of left atrial pressure (LAP)

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End point title

Change from baseline of left atrial pressure (LAP)

End point description

End point type

Secondary

End point timeframe

baseline, prior to each dose escalation, and at 24 hr. post end of infusion

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	0 ^[16]	0 ^[17]	0 ^[18]
Units: mmHg
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[16] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[17] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[18] - Data analysis was not done as limited set of data would preclude meaningful interpretation

No statistical analyses for this end point

Secondary: Change from baseline of pulmonary artery pressure (PAP– systolic and diastolic)

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End point title

Change from baseline of pulmonary artery pressure (PAP– systolic and diastolic)

End point description

End point type

Secondary

End point timeframe

baseline, prior to each dose escalation, and at 24 hr. post end of infusion

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	0 ^[19]	0 ^[20]	0 ^[21]
Units: mmHg
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[19] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[20] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[21] - Data analysis was not done as limited set of data would preclude meaningful interpretation

No statistical analyses for this end point

Secondary: Change from baseline of central venous and arterial oxygen saturation

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End point title

Change from baseline of central venous and arterial oxygen saturation

End point description

End point type

Secondary

End point timeframe

baseline, prior to each dose escalation, and at 24 hr. post end of infusion

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	0 ^[22]	0 ^[23]	0 ^[24]
Units: percentage
number (not applicable)

Notes
[22] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[23] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[24] - Data analysis was not done as limited set of data would preclude meaningful interpretation

No statistical analyses for this end point

Secondary: Change from baseline of urine output

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End point title

Change from baseline of urine output

End point description

End point type

Secondary

End point timeframe

baseline, prior to each dose escalation, and at 24 hr. post end of infusion

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	0 ^[25]	0 ^[26]	0 ^[27]
Units: ml/kg/hour
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[25] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[26] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[27] - Data analysis was not done as limited set of data would preclude meaningful interpretation

No statistical analyses for this end point

Secondary: Change from baseline of blood lactate levels

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End point title

Change from baseline of blood lactate levels

End point description

End point type

Secondary

End point timeframe

baseline, prior to each dose escalation, and at 24 hr. post end of infusion

End point values	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Number of subjects analysed	0 ^[28]	0 ^[29]	0 ^[30]
Units: mmol/L
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[28] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[29] - Data analysis was not done as limited set of data would preclude meaningful interpretation
[30] - Data analysis was not done as limited set of data would preclude meaningful interpretation

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Serelaxin: Cohort 1

Reporting group description

Reporting group title

Serelaxin: Cohort 2

Reporting group description

Reporting group title

Serelaxin: Cohort 3

Reporting group description

Serelaxin was administered intravenously on top of standard therapy for acute heart failure, for a total of 48 hours. In Cohort 3, patients in age group of 1 month to <1 year were enrolled either into a low dose or a high-dose group. During this 48-hour treatment period, the serelaxin dose rates to be administered were 3 μg/kg/day, 10 μg/kg/day and 30 μg/kg/day in the low -dose group; 10 μg/kg/day, 30 μg/kg/day and 100 μg/kg/day in the high-dose group. In this cohort, high- dose group was planned to receive twice the number of patients in low-dose group.

Serious adverse events	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 8 (37.50%)	1 / 3 (33.33%)	0 / 1 (0.00%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Vascular disorders
Hypotension
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subclavian vein thrombosis
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vena cava thrombosis
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial thrombosis
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pleural effusion
subjects affected / exposed	2 / 8 (25.00%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0.5%

Non-serious adverse events	Serelaxin: Cohort 1	Serelaxin: Cohort 2	Serelaxin: Cohort 3
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 8 (75.00%)	3 / 3 (100.00%)	0 / 1 (0.00%)
Vascular disorders
Hypotension
subjects affected / exposed	2 / 8 (25.00%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	2	0	0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Respiratory, thoracic and mediastinal disorders
Pleural effusion
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences all number	0	1	0
Psychiatric disorders
Insomnia
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Investigations
Blood pressure systolic decreased
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Cardioactive drug level increased
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Cardiac disorders
Supraventricular extrasystoles
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Tachycardia
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Ventricular tachycardia
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Nervous system disorders
Headache
subjects affected / exposed	2 / 8 (25.00%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	3	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Nausea
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Skin and subcutaneous tissue disorders
Hyperhidrosis
subjects affected / exposed	1 / 8 (12.50%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences all number	1	1	0
Night sweats
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Skin oedema
subjects affected / exposed	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences all number	0	1	0
Pain in extremity
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences all number	0	1	0
Infections and infestations
Pneumonia viral
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences all number	0	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences all number	0	1	0
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences all number	0	1	0
Hypochloraemia
subjects affected / exposed	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 1 (0.00%)
occurrences all number	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

10 Mar 2014

No patients had entered this study at the time of this amendment. Health Authority review of the original protocol resulted in study design changes regarding the starting dose (low dose group was added) and the patient sample size. Additional analyses were added with regard to vital signs and adverse events. Feedback from pediatric cardiology experts led to small changes to the exclusion criteria and clarification regarding the criteria for inclusion of patients with a chest x-ray done as part of their standard-of-care.

20 Aug 2014

No patients had entered the study at the time this amendment was prepared. This amendment mainly described the sub-study regarding additional data collection that was to be conducted in a small number of participating study sites (1-2 sites), which would enable a more in depth exploration of serelaxin’s PK-PD relationship

30 Sep 2016

Fourteen patients had been enrolled in the study at the time this amendment was prepared. The protocol was amended to incorporate changes to enhance the recruitment feasibility for the study without compromising the study objectives or patient safety.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Due to the early termination of the study, the planned analyses were not performed as the limited set of data would preclude meaningful interpretation.

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Clinical trials

Clinical Trial Results:
Multicenter, open-label, dose escalation study to evaluate safety, tolerability and pharmacokinetics of RLX030 in addition to standard of care in pediatric patients from birth to <18 years of age, hospitalized with acute heart failure

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of patients reported with treatment emergent any adverse events, serious adverse events and death

Primary: Number of patients reported with treatment emergent any adverse events, serious adverse events and death

Primary: Pharmacokinetic parameter: Css (steady state concentration)

Primary: Pharmacokinetic parameter: Css (steady state concentration)

Primary: Pharmacokinetic parameter: CL (clearance)

Primary: Pharmacokinetic parameter: CL (clearance)

Secondary: Change from baseline of arterial blood pressure

Secondary: Change from baseline of arterial blood pressure

Secondary: Change from baseline of central venous pressure (CVP)

Secondary: Change from baseline of central venous pressure (CVP)

Secondary: Change from baseline of left atrial pressure (LAP)

Secondary: Change from baseline of left atrial pressure (LAP)

Secondary: Change from baseline of pulmonary artery pressure (PAP– systolic and diastolic)

Secondary: Change from baseline of pulmonary artery pressure (PAP– systolic and diastolic)

Secondary: Change from baseline of central venous and arterial oxygen saturation

Secondary: Change from baseline of central venous and arterial oxygen saturation

Secondary: Change from baseline of urine output

Secondary: Change from baseline of urine output

Secondary: Change from baseline of blood lactate levels

Secondary: Change from baseline of blood lactate levels

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results: Multicenter, open-label, dose escalation study to evaluate safety, tolerability and pharmacokinetics of RLX030 in addition to standard of care in pediatric patients from birth to <18 years of age, hospitalized with acute heart failure

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of patients reported with treatment emergent any adverse events, serious adverse events and death

Primary: Number of patients reported with treatment emergent any adverse events, serious adverse events and death

Primary: Pharmacokinetic parameter: Css (steady state concentration)

Primary: Pharmacokinetic parameter: Css (steady state concentration)

Primary: Pharmacokinetic parameter: CL (clearance)

Primary: Pharmacokinetic parameter: CL (clearance)

Secondary: Change from baseline of arterial blood pressure

Secondary: Change from baseline of arterial blood pressure

Secondary: Change from baseline of central venous pressure (CVP)

Secondary: Change from baseline of central venous pressure (CVP)

Secondary: Change from baseline of left atrial pressure (LAP)

Secondary: Change from baseline of left atrial pressure (LAP)

Secondary: Change from baseline of pulmonary artery pressure (PAP– systolic and diastolic)

Secondary: Change from baseline of pulmonary artery pressure (PAP– systolic and diastolic)

Secondary: Change from baseline of central venous and arterial oxygen saturation

Secondary: Change from baseline of central venous and arterial oxygen saturation

Secondary: Change from baseline of urine output

Secondary: Change from baseline of urine output

Secondary: Change from baseline of blood lactate levels

Secondary: Change from baseline of blood lactate levels

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
Multicenter, open-label, dose escalation study to evaluate safety, tolerability and pharmacokinetics of RLX030 in addition to standard of care in pediatric patients from birth to <18 years of age, hospitalized with acute heart failure