Table 1.

Major phase 2 clinical trials on serelaxin

Clinical trial (Acronym)	Clinical trials. Gov identifier	Participants	CV condition	Intervention	Study duration	Main results
A multicenter, double-blind, randomized, parallel group, placebo-controlled study to evaluate the effects of intravenous serelaxin infusion on micro and macrovascular function in patients with coronary artery disease [38]	NCT01979614	- 58 Follow-up: 6 months Inclusion criteria: - > 18 years with proven obstructive CAD Exclusion criteria - AHF at baseline - HF NYHA Class III–IV	CAD	Treatment group Serelaxin: 30 μg/kg/day Control group Placebo	November 2013 to August 2016	- Significant BP reductions at 2 h (P = 0.0003) and 6 h (P = 0.001) - No significant change in MBF at rest (P = 0.40) or during stress (P = 0.76) - No significant change at 47 h in global MPR, in Alx or in aortic stiffness (P > 0.05 for all) - No significant change in PWV up to day 180 (P > 0.05 for all) - Significant decrease in cystatin C and endothelin-1 - No statistically significant changes in ventricular volumes and ejection fractions - Similar numbers of SAEs between treatment groups
Relaxin for the treatment of patients with acute heart failure: a multicentre, randomized, placebo-controlled, parallel-group, dose-finding phase IIb study (Pre-RELAX-AHF) [21]	NCT00520806	- 234 Follow-up: 6 months Time to randomization ± SD (hours): 8.4 ± 5.35 Inclusion criteria: - Within 16 h of presentation for AHF - SBP > 125 mm Hg - eGFR of 30–75 mL/min per 1.3 m2	AHF	Group 1 Relaxin:10 μg/kg/day for 48 h Group 2 Relaxin: 30 μg/kg/day for 48 h Group 3 Relaxin:100 μg/kg/day for 48 h Group 4 Relaxin 250: μg/kg/day for 48 h Control group Placebo for 48 h	December 2007 to August 2008	- Significant improvement in dyspnea at 24 h (P = 0.044) and up to day 14 (P = 0.053) - Significant reduction of CV death or readmission at 60 days (P = 0.053) - Decreased death due to HF or renal failure at day 60 (relaxin 6.1% vs placebo 17.2%) - Decreased all-cause mortality (P = 0.17) and CV mortality (P = 0.14) at day 180 - Decrease WHF through day 5 (P = 0.29) - Increased number of days alive out of the hospital by day 60 (P = 0.16) and decreased LoS (P = 0.18) - Similar number of AEs between groups
Pharmacokinetics & safety of serelaxin on top of standard of care therapy in pediatric patients with acute heart failure (RELAX-PEDS-PK) [23]	NCT02151383	- 12 Group 1 - 6 to < 18 years Group 2 - 1 to < 6 years Group 3 - 1 month to < 1 year Inclusion criteria: Hospitalized with AHF	AHF	Treatment - Low dose for 48 h 3, 10, 30 ug/kg/Day or - High dose for 48 h 10,30, 100 ug/kg/Day	May 2014 to April 2017	- Results not analyzed due to early termination - Number of patients with treatment-emergent AEs, SAEs, and death - Pharmacokinetic concentrations for low dose and high dose intervention
Study of safety, tolerability and pharmacokinetics of serelaxin in Japanese Acute Heart Failure (AHF) patients (RELAX-AHF-JAPAN) [56]	NCT02002702	- 46 Follow-up: 60 days Time to randomization (hours): 8.2 Mean age ± SD (years) Group 1: 70.2 ± 11.8 Group 2: 79.7 ± 9.0 Control: 76.4 ± 12.1	AHF	Group 1: 10 µg/kg/day serelaxin 48 h Group 2: 30 µg/kg/day serelaxin 48 h Control group: Placebo	August 2014	- Greater reduction in SBP with 10 µg/kg/day serelaxin compared to placebo - Greater reductions in NT-proBNP in 10 and 30 µg/kg/day serelaxin at day 2 and day 5 compared to placebo - AEs profile comparable between treatment groups
Safety of repeat doses of IV serelaxin in subjects with chronic heart failure (RELAX-REPEAT) [51, 57]	NCT01982292	- 321 Follow-up: 16 weeks Inclusion criteria: compensated CHF (NYHA Class II–III)	CHF	Treatment group Serelaxin: 30 μg/kg/day Control group Placebo	November 2013 to September 2015	- Non-statistically significant increase in the proportion of patient’s antibody positive - No confirmed hypersensitivity or infusion-related reactions in any treatment group - Statistically significant decreases in cystatin-C - Statistically significant increases in eGFR - Improved renal function following 48 h serelaxin - AEs profile comparable between groups
Study of the Effect of Serelaxin on High-sensitivity Cardiac Troponin I (Hs-cTnI) Release in Patients With Chronic Heart Failure (RELAX-CARDIO) [58]	NCT02625922	- 26 Mean age ± SD (years) Serelaxin -Placebo group: 74.7 ± 7.62 Placebo -Serelaxin group: 66.5 ± 13.89	CHF	IV Serelaxin (weight-range adjusted dosing regimen) IV Matching placebo (adjusted dosing regimen) Serelaxin -placebo treatment group: Subjects received serelaxin in treatment period 1 and placebo in treatment period 2 Placebo -Serelaxin Treatment group: Subjects received placebo in treatment period 1 and serelaxin in treatment period 2	December 2015 to January 2017	- Geometric mean of Hs-cTnI concentration after exercise compared to placebo The study was terminated early by Novartis, 19-Apr-2017 - hs-cTnI assay was not completed, and the primary efficacy endpoint was not analyzed

It includes the information on target disease, patient population, intervention dosage and key findings

IV intravenous, SD standard deviation, CV cardiovascular, CAD coronary artery disease, AHF acute heart failure, NYHA New York heart association, HF heart failure, LoS length of stay, WHF worsening heart failure, CHF congestive heart failure, eGFR estimated glomerular filtration rate, AEs adverse events, SAEs serious adverse events, BP blood pressure, SBP systolic blood pressure, MPR myocardial perfusion rate, MBF myocardial blood flow, PWV pulse wave velocity, Alx augmentation index, Hs-cTnI high-sensitivity cardiac troponin I, NT-proBNP N-terminal (NT)-pro hormone BNP