QUantum Genomics Incremental Dosing in Heart Failure - QUID-HF (QUID-HF)
11 de octubre de 2018 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
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 de estudio
Intervencionista
Inscripción (Actual)
23
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Berlin, Alemania
- Charity Universitatsmedizin Berlin
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Hannover, Alemania, D-30625
- Medizinische Hochschule Hannover
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Homburg, Alemania, 66421
- Klinik für Innere Medizin III
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Frýdek-Místek, Chequia, 73801
- Hospital of Fridek-Mistek P.O.
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Praha, Chequia, 12808
- General University Hospital
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Bron, Francia, 69677
- Hopital Louis Pradel
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Montpellier, Francia, 34295
- Hopital Arnaud de Villeneuve
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Nancy, Francia, 54500
- CHRU NANCY
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Nantes, Francia, 44093
- Hôpital Laennec
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Paris, Francia, 75013
- Hôpital Pitie Salpétrière
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Paris, Francia, 75015
- Georges Pompidou European Hospital
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Rouen, Francia, 76031
- Hôpital Charles Nicolle
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Strasbourg, Francia, 67000
- Hopitaux Universitaires de Strasbourg
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Toulouse, Francia, 31000
- Clinique Pasteur
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Budapest, Hungría, 1134
- Magyar Honvedseg Egeszsegugyi Kozpont
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Budapest, Hungría, 1122
- Heart and Vascular Center of Semmelweis University
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Stavanger, Noruega, 4011
- Stavanger University Hospital
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Groningen, Países Bajos, 9713GZ
- University Medical Center Groningen
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Maastricht, Países Bajos, PO 5800
- Maastricht University Medical Centre
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Wroclaw, Polonia, 50981
- Clinical Military Hospital
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Łódź, Polonia, 94048
- NZOZ All-Med Centrum Medyczne
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Dundee, Reino Unido, DD1 9SY
- Ninewells Hospital
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England
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Birmingham, England, Reino Unido, B18 7QH
- University of Birmingham Institute of Cardiovascular Sciences City Hospital,
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: QGC001
QGC001 from 50mg to 500mg capsule twice daily, for 28 days, oral use
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Comparador de placebos: Placebo
Placebo, capsule twice daily, for 28 days, oral use
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Lactose capsule manufactured to mimic QGC001 50 mg and 250 mg
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Relative decrease in NT-proBNP
Periodo de tiempo: 28 days
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Percentage of subjects with a relative decrease in NT-proBNP of more than 30% from Baseline to day 28.
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28 days
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Blood pressure change
Periodo de tiempo: 28 days
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Blood pressure changes at each visit (D7, D14, D21, D28), compared to the Baseline measure
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28 days
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Blood biochemistry
Periodo de tiempo: 35 days
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blood biochemistry at D7, D14, D21, D28 and D35.
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35 days
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Urinary biochemistry
Periodo de tiempo: 35 days
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electrolytes, urinary osmolarity at D7, D14, D21, D28 and D35.
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35 days
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Change of NT-proBNP
Periodo de tiempo: 35 days
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Changes in central lab values of NT-proBNP at D7, D14, D21, D28 and D35.
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35 days
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Change of BNP
Periodo de tiempo: 35 days
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Changes in central lab values of BNP at D7, D14, D21, D28 and D35.
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35 days
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Change of selected biomarker levels
Periodo de tiempo: 28 days
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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
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28 days
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Quality of life Minnesota Living with Heart Failure Score
Periodo de tiempo: 28 days
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Quality of life Minnesota Living with Heart Failure Score and D0 and Day 28
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28 days
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Faiez Zannad, MD, Centre d'investigation clinique CHU-Nancy
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de junio de 2016
Finalización primaria (Actual)
12 de septiembre de 2018
Finalización del estudio (Actual)
12 de septiembre de 2018
Fechas de registro del estudio
Enviado por primera vez
17 de mayo de 2016
Primero enviado que cumplió con los criterios de control de calidad
20 de mayo de 2016
Publicado por primera vez (Estimar)
23 de mayo de 2016
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
16 de octubre de 2018
Última actualización enviada que cumplió con los criterios de control de calidad
11 de octubre de 2018
Última verificación
1 de octubre de 2018
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- QUID-HF_v5.0_20171120
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Descripción del plan IPD
Individual participant date would be available only by the center via eCRF
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .