Clinical Trials

Date: 2016-09-29

Type of information: Presentation of results at a congress

phase: 2a

Announcement: presentation of results at the Congress of the European Society of Hypertension

Company: Quantum Genomics (France)

Product: QGC001

Action mechanism:

• enzyme inhibitor/Brain Aminopeptidase A inhibitor (BAPAI). QGC001 is a Brain Aminopeptidase A inhibitor (BAPAI) product. This candidate is a prodrug that delivers in the brain the EC33 product, a selective and specific inhibitor of Aminopeptidase A, thus preventing the production of Angiontensin III in the brain. Several preclinical studies and two clinical studies have been conducted already using QGC001 to assess its pharmacokinetic, pharmacodynamic, safety and tolerance parameters in animals and humans.

Disease: hypertension

Therapeutic area: Cardiovascular diseases

Country: France

Trial details:

• This randomised double-blind study, with cross-over, will compare the effects of the product QGC001 (500 mg morning and night) with those of a placebo. It also aims to analyse the pharmacodynamic effects of QGC001 on several hormonal biomarkers (measures of concentrations of plasma renin, aldosterone, cortisol, adrenocorticotropin (ACTH), apelin and copeptin, a Vasopressin biomarker, as well as urinary aldosterone and urinary cortisol). (NCT02322450)

Latest news:

• • On June 19, 2017, Quantum Genomics announced that QGC001 showed efficacy in patients with mild to moderate arterial hypertension, according to the results of a Phase IIa pilot study. The results of this study were presented at the Congress of the European Society of Hypertension on June 18 by its principal investigator, Prof Michel Azizi, Director of the Clinical Investigation Center and Head of the Arterial Hypertension Unit at Georges Pompidou European Hospital, Paris. This Phase IIa was planned as a multicentric, randomized, double-blind, crossover study, administered over two periods of four weeks each. The main goal was to assess in 34 patients suffering from Grade I or II arterial hypertension (systolic pressure 40 ? 179 mmHg, diastolic pressure 90 ? 109 mmHg) the effect on blood pressure of QGC001 administered orally at a dose of 250 mg twice a day for one week, then a dose of 500 mg twice a day for three weeks, compared to placebo. Another goal was to assess the safety and tolerance of QGC001 and its effects on the plasma levels of hormones involved in cardiovascular regulation.
• Multivariate data analysis demonstrated the effects of initial blood pressure level (p=0.01) and treatment by QGC001 (p=0.06) on lowering ambulatory systolic blood pressure. The study also showed, despite the small sample size, that QGC001 led to a decrease in ambulatory systolic blood pressure (primary evaluation criterion) of 2.7 mmHg (p=0.16) and in-office systolic blood pressure of 4.7 mm Hg (0=0.15), as compared with placebo where no decrease in blood pressure was observed. The goal of this study was to demonstrate in humans the proof-of-concept obtained in animals and to help define future clinical trials. The conclusions of the study are fully consistent with the experimental results in animals. No effect was found in normotensive rats but a decrease in blood pressure was revealed in hypertensive rats (SHR and DOCA-salt) in which aminopeptidase A is hyperactive as compared to normotensive animals, in the same way as in Phase I in humans, QGC001 led to no decrease in blood pressure in healthy normotensive volunteers. The clinical trial also showed no change in plasma hormone concentrations such as active renin, aldosterone, cortisol, adrenocorticotropic hormone and apelin in either the QGC001 group or placebo, confirming that QGC001's action mechanism is not mediated by renin or aldosterone. The good tolerance observed on renal function as well as on blood electrolytes, such as sodium and potassium, is particularly important from the perspective of the potential use of QGC001 in the treatment of heart failure, an indication for which Quantum Genomics is currently carrying out a pan-European Phase II clinical study. In general, QGC001's tolerance profile is consistent with observations in the Phase I clinical trials. Following FDA  guidance, Quantum Genomics is preparing a larger Phase II study to be launched in autumn 2017 in the United States. Called NEW-HOPE, this study will cover 250 hypertensive patients with higher cardiovascular risks.
• • On September 29, 2016, Quantum Genomics has reported top-line results from its Phase IIa trial of QGC001 in patients with hypertension. The data show positive signals on several endpoints, in particular on the primary endpoint of the study, specifically a drop in daytime systolic blood pressure measured as ambulatory pressure in hypertensive patients, treated with QGC001 as compared with placebo. This positive result is confirmed by an in-depth multivariate analysis. In this double-blind crossover study, a total of 34 patients with moderate Grade I to II hypertension were randomized, and received two 28-day sequences alternating QGC001 versus placebo, separated by a 14-day washout (no treatment) period. The full results of the study will be presented at a major medical meeting. In this respect, Quantum Genomics is targeting the next European Society of Hypertension meeting which will take place in June 2017 in Milan. In addition, Quantum Genomics announced that a Pre-Investigational New Drug (IND) meeting took place with the FDA in Washington. The FDA has reviewed and analyzed the entire QGC001 documentation, including all preclinical and clinical data available to date, particularly the Phase IIa trial methodology and efficacy and tolerance data. Based on the information, the FDA has advised the Company on the design of a Phase II trial to be conducted in the United States to evaluate QGC001 in a targeted population of hypertensive patients. Quantum Genomics plans to submit an IND application for the trial in the first half of 2017. Quantum Genomics is also evaluating the possibility of further clinical trials in Europe and Asia. • On November 25, 2015, the Scientific Advisory Board of Quantum Genomics has just met in Paris. At that meeting, the AdvisoryBoard reviewed the various investigations under way and recommended future development directions and stages. The Scientific Advisory Board discussed broadening the scope of the next clinical trials in Europe and the United States to adopt a multicentric approach, for both high blood pressure (QGC001 program) and heart failure (QGC101 program). Research would be carried out simultaneously by recognized investigators located at different centers but using common protocols and identical procedures. The multicentric approach would combine as many patients as possible to obtain more accurate medical data.
• •  On October 6, 2015, Quantum Genomics announced that the Monitoring Board for the Phase IIa trial of QGC001 met for the first time on 29 September 2015.After analysing all the clinical and biological monitoring data, the Board recommended that the trial continues as planned.
• •  On September 8, 2015, Quantum Genomics announced it has now recruited more than half the patients for its Phase IIa trial of QGC001. This is four months ahead of the recruitment schedule set by the company.
• •  On March 3, 2015, Quantum Genomics announced it has now recruited the first three patients for its Phase IIa trial of its molecule QGC001. This first-in-class drug candidate of the new class of therapeutics for the treatment of high blood pressure, in November 2014 obtained the authorisations from ANSM (the French national drug and health products safety agency) and CPP (the French consumer protection agency) to start Phase IIa trials aimed at proving its effectiveness in hypertensive patients. The clinical trials will be conducted on some 30 patients with grade 1 high blood pressure (systolic pressure > 140 and ? 159 mmHg; diastolic pressure > 90 and ? 99 mmHg) or with grade 2 high blood pressure (systolic pressure > 160 mmHg; diastolic pressure > 100 mmHg). The study involves four clinical investigation centres in France, under the supervision of Prof. Michel Azizi (Clinical Investigation Centre at Georges Pompidou European Hospital, Paris) as part of the CLINAPAI collaborative programme, subsidised by the French National Research Agency (ANR). The four French centres, named “Centres of Excellence” by the European Society of Hypertension (ESH), participating in this clinical trial are:the Georges Pompidou European Hospital, Paris; the Croix Rousse Hospital, Lyon; the Cardiology Hospital – Lille Regional University Hospital Centre; the Arthur Gardiner Hospital, Dinard. Quantum Genomics’ goal is to sign, by the end of 2016, a license agreement or partnership with a manufacturer in the healthcare sector to continue the clinical development of its product QGC001, its registration and commercialisation.
• • On November 17, 2014, Quantum Genomics, a biopharmaceutical company with the mission of developing new therapies for unmet medical needs in the field of cardiovascular diseases, announced that it received the approvals of ANSM (French Drug Administration) and CPP (Patient Protection Committee) to start a Phase IIa clinical trial using its lead compound QGC001, a first-in-class drug candidate to treat hypertension. QGC001 could be a therapeutic solution for poorly or not controlled patients, especially those with a specific hormonal profile characterized by Low Renin and High Vasopressin (LRHV), whose blood pressure is very difficult to regulate by using classical blockers of the systemic renin-angiotensin pathways. QGC001 and its therapeutic use are strongly protected by several patent families. Preclinical and Phases Ia and Ib studies generated positive data regarding QGC001 safety, tolerance, pharmacokinetics and pharmacodynamics in animal and human.Quantum Genomics will continue the clinical development of QGC001 by starting a clinical trial Phase IIa to demonstrate its efficacy in hypertensive patients. The trial will involve several clinical investigation centers in France. Professor Michel Azizi, head of the clinical investigation center at European Hospital Georges Pompidou in Paris, will be the principal investigator.

Is general: Yes