QUantum Genomics Incremental Dosing in Heart Failure - QUID-HF

NCT02780180 | Terminated Phase 2 DMC

• 1 other identifier: QUID-HF_v5.0_20171120
• Study Type: interventional
• Target: 23
• Locations: 8 countries
• Sites: 23

Brief Summary

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.

Conditions

Heart Failure

Keywords

Aminopeptidase A inhibitor; Heart Failure; Up-titration; Dose-Response Relationship, Drug; Pharmacokinetics; Patient Safety; Treatment Efficacy

Outcome Measures

Primary Outcomes (2)

• Relative decrease in NT-proBNP

  Percentage of subjects with a relative decrease in NT-proBNP of more than 30% from Baseline to day 28.

  28 days

• Blood pressure change

  Blood pressure changes at each visit (D7, D14, D21, D28), compared to the Baseline measure

  28 days

Secondary Outcomes (6)

• Blood biochemistry

  35 days

• Urinary biochemistry

  35 days

• Change of NT-proBNP

  35 days

• Change of BNP

  35 days

• Change of selected biomarker levels

  28 days

Study Arms (2)

QGC001

EXPERIMENTAL

QGC001 from 50mg to 500mg capsule twice daily, for 28 days, oral use

Drug: QGC001

Placebo

PLACEBO COMPARATOR

Placebo, capsule twice daily, for 28 days, oral use

Drug: Placebo

Interventions

QGC001 DRUG

QGC001

Placebo DRUG

Lactose capsule manufactured to mimic QGC001 50 mg and 250 mg

Placebo

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Quantum Genomics SA: lead

Study Sites (23)

Hospital of Fridek-Mistek P.O.

Frýdek-Místek, 73801, Czechia

Location

General University Hospital

Prague, 12808, Czechia

Location

Hôpital Louis Pradel

Bron, 69677, France

Location

Hopital Arnaud de Villeneuve

Montpellier, 34295, France

Location

CHRU Nancy

Nancy, 54500, France

Location

Hôpital Laennec

Nantes, 44093, France

Location

Hôpital Pitié Salpêtrière

Paris, 75013, France

Location

Georges Pompidou European Hospital

Paris, 75015, France

Location

hôpital Charles Nicolle

Rouen, 76031, France

Location

Hôpitaux universitaires de Strasbourg

Strasbourg, 67000, France

Location

Clinique Pasteur

Toulouse, 31000, France

Location

Charity Universitatsmedizin Berlin

Berlin, Germany

Location

Medizinische Hochschule Hannover

Hanover, D-30625, Germany

Location

Klinik für Innere Medizin III

Homburg, 66421, Germany

Location

Heart and Vascular Center of Semmelweis University

Budapest, 1122, Hungary

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, 1134, Hungary

Location

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

Location

Maastricht University Medical Centre

Maastricht, PO 5800, Netherlands

Location

Stavanger University Hospital

Stavanger, 4011, Norway

Location

NZOZ ALL-MED Centrum Medyczne

Lodz, 94048, Poland

Location

Clinical Military Hospital

Wroclaw, 50981, Poland

Location

University of Birmingham Institute of Cardiovascular Sciences City Hospital,

Birmingham, England, B18 7QH, United Kingdom

Location

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Faiez Zannad, MD

  Centre d'investigation clinique CHU-Nancy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: May 23, 2016
• Study Start: June 1, 2016
• Primary Completion: September 12, 2018
• Study Completion: September 12, 2018
• Last Updated: October 16, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); NO (1); PL (2); NL (2); FR (9); CZ (2); HU (2); GB (2)