Study of the Effect of Serelaxin on High-sensitivity Cardiac Troponin I (Hs-cTnI) Release in Patients With Chronic Heart Failure

NCT02625922 | Terminated Phase 2 Results DMC

• 2 other identifiers: CRLX030A22112015-002673-38
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 9

Brief Summary

This was a multicenter, randomized, double-blind, crossover, placebo-controlled, Phase II clinical study that evaluated the effect of serelaxin versus placebo (both in addition to SoC) on the release of hs-cTnI, in patients with CHF after an exercise testing session.

Conditions

Chronic Heart Failure

Keywords

Serelaxin,; Chronic heart failure,; Spiroergometry,; Troponin,; New York Heart Association (NYHA) functional Class II/III,; Left ventricular ejection fraction,

Outcome Measures

Primary Outcomes (1)

• Geometric Mean of High Sensitivity Cardiac Troponin I (Hs-cTnI) Concentration After Exercise Compared to Placebo

  This cardiac biomarker measurement was obtained to determine plasma concentrations following a cardiac stress test.

  Baseline, up to 7 hours after the start of an exercise testing session on treatment period 1 (Day 1) and treatment period 2 (Day 15+/- 1)

Secondary Outcomes (3)

• Geometric Mean of High Sensitivity Cardiac Troponin I (Hs-cTnI) Concentrations After Exercise Compared to Placebo at 4 and 5 Hours

  4 and 5 hours after exercise testing session

• Log-transformed Concentration of N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Concentrations Compared to Placebo

  Baseline, up to 7 hours after the start of an exercise testing session on treatment period 1 (Day 1) and treatment period 2 (Day 15 +/- 1)

• Log-transformed Concentration Values of Heart-type Fatty Acid-binding Protein (H-FABP) Concentrations Compared to Placebo

  Baseline, up to 7 hours after the start of an exercise testing session on treatment period 1 (Day 1) and treatment period 2 (Day 15 +/- 1)

Study Arms (2)

Serelaxin followed by Placebo

EXPERIMENTAL

On Day 1 of treatment period 1, Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen The routine exercise assessment will commence at minute 120. In treatment period 2, on day 15 ± 1-day washout, matching placebo will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen.

Drug: Serelaxin; Drug: Placebo

Placebo followed by Serelaxin

EXPERIMENTAL

On Day 1 of treatment period 1, matching placebo will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen The routine exercise assessment will commence at minute 120. In treatment period 2, on day 15 ± 1-day washout, Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen.

Drug: Serelaxin; Drug: Placebo

Interventions

Serelaxin DRUG

Serelaxin will be administered as a continuous i.v. infusion according to a weight-range adjusted dosing regimen

Also known as: RLX030

Placebo followed by Serelaxin; Serelaxin followed by Placebo

Placebo DRUG

Matching placebo i.v infusion

Placebo followed by Serelaxin; Serelaxin followed by Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female ≥ 18 years of age, with body weight ≤ 160 Kg
• Diagnosis of stable CHF:
• New York Heart Association (NYHA) functional Class II/III.
• Receiving guideline-recommended treatment for CHF.
• Left ventricular ejection fraction \< 45%, obtained within the last 3 months prior to screening.
• NT-proBNP \> 300 ng/L in sinus rhythm or \> 900 ng/L if not in sinus rhythm (determined locally).
• Ability to exercise for at least 10 to 12 minutes based on investigator's judgment.
• Systolic BP ≥ 125 mmHg at randomization
• Renal function defined as an eGFR of ≥ 25 mL/min/1.73 m\^2 at screening (sMDRD formula).

You may not qualify if:

• Dyspnea primarily due to non-cardiac causes.
• Increased risk of developing hypotension during vasodilator therapy according to investigators judgement.
• Any contraindication for exercise testing and spirometry.
• Stopping of the spiroergometry at screening according to the stopping rules, unless the patient has reached maximum exercise capacity defined as carbon dioxide production/oxygen consumption (VCO2/VO2) \> 1.05.
• Change in guideline-recommended CHF treatment within 1 month prior to screening.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

Greifswald, Mecklenburg-Vorpommern, 17475, Germany

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

München, 80636, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Hull, HU16 5JQ, United Kingdom

Location

Novartis Investigative Site

London, SW 6NP, United Kingdom

Location

Novartis Investigative Site

Tyne and Wear, NE2 4HH, United Kingdom

Location

MeSH Terms

Interventions

serelaxin protein, human

Limitations and Caveats

The study was terminated early by Novartis, 19-Apr-2017. Because of the early termination of the study, the validation of the hs-cTnI assay was not completed and the primary efficacy endpoint was not analyzed.

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2015
• First Posted: December 9, 2015
• Study Start: February 5, 2016
• Primary Completion: January 11, 2017
• Study Completion: January 11, 2017
• Last Updated: September 21, 2018
• Results First Posted: September 21, 2018

Record last verified: 2018-01

Locations

DE (5); CH (1); GB (3)