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QUantum Genomics Incremental Dosing in Heart Failure - QUID-HF (QUID-HF)

11 ottobre 2018 aggiornato da: Quantum Genomics SA

A Randomized, Double-blind, Multi-centre Study to Assess Safety and Efficacy of Incremental Doses of QGC001 in Patients With NYHA Class II/III Chronic Heart Failure (HF) With Left Ventricular Systolic Dysfunction Versus Placebo.

Heart Failure (HF) a common clinical condition characterized by either by a heart that does not pump sufficiently or becomes stiff. A variety of mechanisms contribute to progressive cardiac remodeling and dysfunction.

A new therapeutic approaches by preventing activation of the brain neuromodulatory pathway, may lead to improve HF.

QCG001 is a prodrug of EC33, a aminopeptidase A (APA) inhibitor. QCG001 has been shown to be an antihypertensive agent in animal models.

This study investigates the safety and efficacy of QGC001 in HF patients.

Panoramica dello studio

Stato

Terminato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Despite advances in care, prognosis remains poor once overt Heart Failure (HF) has developed. HF is a common clinical condition characterized by either by a heart that does not pump sufficiently or becomes stiff and it is associates with higher incidences of patient illness and death in both case. A variety of mechanisms contribute to progressive cardiac remodeling and dysfunction.

A new therapeutic approaches by preventing activation of the brain neuromodulatory pathway, may lead to improve HF.

QCG001 is a prodrug of EC33, a specific and selective of the aminopeptidase A (APA) inhibitor. QCG001 has been shown to be an antihypertensive agent in animal models.

This study investigates the safety and efficacy of QGC001 up-titrated form 50mg twice daily to a maximum of 500 mg twice daily, on patients with worsening chronic HF during 28 days and 7 days after discontinuation (day 35).

6 European countries are involved in this study (France, Netherlands, Germany, Norway, Poland and United Kingdom) including 20 investigational hospitals. Patients would be followed during 35 days and inclusion period lasts until December 2017.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

23

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Cechia
      • Frýdek-Místek, Cechia, 73801
        • Hospital of Fridek-Mistek P.O.
      • Praha, Cechia, 12808
        • General University Hospital
  • Francia
      • Bron, Francia, 69677
        • Hopital Louis Pradel
      • Montpellier, Francia, 34295
        • Hopital Arnaud de Villeneuve
      • Nancy, Francia, 54500
        • CHRU NANCY
      • Nantes, Francia, 44093
        • Hôpital Laennec
      • Paris, Francia, 75013
        • Hôpital Pitie Salpétrière
      • Paris, Francia, 75015
        • Georges Pompidou European Hospital
      • Rouen, Francia, 76031
        • Hôpital Charles Nicolle
      • Strasbourg, Francia, 67000
        • Hopitaux Universitaires de Strasbourg
      • Toulouse, Francia, 31000
        • Clinique Pasteur
  • Germania
      • Berlin, Germania
        • Charity Universitatsmedizin Berlin
      • Hannover, Germania, D-30625
        • Medizinische Hochschule Hannover
      • Homburg, Germania, 66421
        • Klinik für Innere Medizin III
  • Norvegia
      • Stavanger, Norvegia, 4011
        • Stavanger University Hospital
  • Olanda
      • Groningen, Olanda, 9713GZ
        • University Medical Center Groningen
      • Maastricht, Olanda, PO 5800
        • Maastricht University Medical Centre
  • Polonia
      • Wroclaw, Polonia, 50981
        • Clinical Military Hospital
      • Łódź, Polonia, 94048
        • NZOZ All-Med Centrum Medyczne
  • Regno Unito
      • Dundee, Regno Unito, DD1 9SY
        • Ninewells Hospital
    • England
      • Birmingham, England, Regno Unito, B18 7QH
        • University of Birmingham Institute of Cardiovascular Sciences City Hospital,
  • Ungheria
      • Budapest, Ungheria, 1134
        • Magyar Honvedseg Egeszsegugyi Kozpont
      • Budapest, Ungheria, 1122
        • Heart and Vascular Center of Semmelweis University

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • A signed and dated informed consent form prior to any study procedure
  • Adult male subjects and female subjects without childbearing potential.
  • Clinical diagnosis of CHF with history of NYHA class II-III for at least 3 months before randomisation.
  • Documented left ventricular ejection fraction (LVEF) < 40% measured by any modality within the previous 12 months in the subject's medical history.
  • Subjects must also have at least one local measurement of BNP level ≥ 300 pg/mL or NT-proBNP level ≥ 1200 pg/mL (preferred assay, local laboratory) at the screening visit (maximum 7 days before randomisation).
  • eGFR > 30 mL/min/1.73 m2 (MDRD) at screening.
  • Serum potassium < 5.0 mmol/L at screening.
  • Systolic blood pressure < 110 mmHg (average of 3 consecutive measurements) at screening.
  • Prescribed to optimal pharmacologic therapy per "ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2016", or based on the updated current clinical practice, unless contra-indicated or not-tolerated, and on a stable dose for at least 30 days prior to enrolment (the dosage of the drugs cannot be increased or decreased respectively by more than double or half of initial dosage).
  • Taking oral loop diuretics at doses < 250 mg furosemide daily (or equivalent).

Exclusion Criteria:

  • BMI > 45 kg.m-2.
  • Patients who require the use of HF IV therapy or oral furosemide > 250 mg (or equivalent) at any time during the 48 hours immediately before randomisation.
  • Patients with unstable angina, myocardial infarction, PTCA, coronary artery bypass graft, cerebral vascular accident, or transient ischemic attack within previous 3 months (90 days) before enrolment.
  • Patients whose primary cause of heart failure is mitral or aortic valve disease or congenital heart disease or hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy (e.g. amyloidosis, sarcoidosis) or myocarditis.
  • Patients with "new" permanent atrial fibrillation (AF), discovered within 3 months prior to randomization.
  • Heart rate > 110 beats/min at screening.
  • Patients scheduled for Pacemaker (including ICD, CRT), Angioplasty, CABG or LVAD within the next 3 months.
  • Patients with severe documented chronic obstructive lung disease (COPD), defined as chronic need for oxygen therapy
  • eGFR < 30 mL/min/1.73 m2 (MDRD) at screening.
  • Decrease in eGFR greater than 20% within 3 weeks prior to the screening visit.
  • Serum potassium > 5.0 mmol/L at screening.
  • Systolic blood pressure < 110 mmHg or with signs or symptoms of hypotension.
  • Symptomatic hypotension or orthostatic hypotension defined by a decrease of systolic blood pressure of more than 30 mm Hg in the standing vs. sitting position at screening and at the basal SBP of the D0 (before having taken the study medication).
  • A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstrated of a QTc interval > 450 ms) AND QRS < 100 ms. In case of QRS enlargement > 100 ms (i-e bundle branch block, pacemakers) QT does not accurately reflect repolarization and may not be calculated.
  • A history of additional risk factors for Torsade de Pointes (TdP) (e.g. hypokalemia, family history of long QT Syndrome).
  • The use of concomitant medications that prolong the QT/QTc interval.
  • Insulin-requiring diabetic patients (including type 1 Diabetes).
  • History of angioneurotic edema.
  • Severe liver failure at screening defined by a value of ALAT and/or ASAT≥ 5 from the normal value.
  • Patients involved in any interventional clinical study, patients enrolled in Registries and/or in non-interventional studies may participate.
  • Patients who take an investigational or non-approved treatment.
  • Women of childbearing potential.
  • Patients with a prior cardiac transplant or patients currently on the list for cardiac transplantation.
  • Patient with hypersensitivity to the active substance or to one of the other components of the trial preparation.
  • Patients in whom an allergy requiring chronic treatment is known or exists.
  • Patients with a history of previous illnesses of neurological or psychiatric nature that affect the Central Nervous System.
  • Patients with a life expectancy of less than 12 months per physician judgment.
  • Frail patient who, in the opinion of the investigator will not be able to follow the protocol.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: QGC001
QGC001 from 50mg to 500mg capsule twice daily, for 28 days, oral use
Droga: QGC001
Comparatore placebo: Placebo
Placebo, capsule twice daily, for 28 days, oral use
Droga: Placebo
Lactose capsule manufactured to mimic QGC001 50 mg and 250 mg

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Relative decrease in NT-proBNP
Lasso di tempo: 28 days
Percentage of subjects with a relative decrease in NT-proBNP of more than 30% from Baseline to day 28.
28 days
Blood pressure change
Lasso di tempo: 28 days
Blood pressure changes at each visit (D7, D14, D21, D28), compared to the Baseline measure
28 days

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Blood biochemistry
Lasso di tempo: 35 days
blood biochemistry at D7, D14, D21, D28 and D35.
35 days
Urinary biochemistry
Lasso di tempo: 35 days
electrolytes, urinary osmolarity at D7, D14, D21, D28 and D35.
35 days
Change of NT-proBNP
Lasso di tempo: 35 days
Changes in central lab values of NT-proBNP at D7, D14, D21, D28 and D35.
35 days
Change of BNP
Lasso di tempo: 35 days
Changes in central lab values of BNP at D7, D14, D21, D28 and D35.
35 days
Change of selected biomarker levels
Lasso di tempo: 28 days
Changes in central lab values from baseline in selected biomarker levels (biomarkers involved in the pathophysiology of the disease, which will be decided later) at Day 7, Day 14, Day 21, Day 28
28 days
Quality of life Minnesota Living with Heart Failure Score
Lasso di tempo: 28 days
Quality of life Minnesota Living with Heart Failure Score and D0 and Day 28
28 days

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Quantum Genomics SA

Investigatori

  • Investigatore principale: Faiez Zannad, MD, Centre d'investigation clinique CHU-Nancy

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 giugno 2016

Completamento primario (Effettivo)

12 settembre 2018

Completamento dello studio (Effettivo)

12 settembre 2018

Date di iscrizione allo studio

Primo inviato

17 maggio 2016

Primo inviato che soddisfa i criteri di controllo qualità

20 maggio 2016

Primo Inserito (Stima)

23 maggio 2016

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

16 ottobre 2018

Ultimo aggiornamento inviato che soddisfa i criteri QC

11 ottobre 2018

Ultimo verificato

1 ottobre 2018

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • QUID-HF_v5.0_20171120

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Descrizione del piano IPD

Individual participant date would be available only by the center via eCRF

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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