Randomized study of Extended treatment with Firibastat in treatment-RESistant Hypertensio

Phase 1

• Conditions: Treatment of patients with difficult-to-treat and/or treatment-resistant hypertension (HTN); MedDRA version: 21.1Level: LLTClassification code 10036695Term: Primary hypertensionSystem Organ Class: 100000004866; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2021-001404-14-SK
• Lead Sponsor: Quantum Genomics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-08
• Last Update Posted: 30 January 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 750

Inclusion Criteria

1. Able to understand and willing to provide written informed consent,
and able to comply with the study procedures and restrictions.
2. Adult men and women (at Screening). For all countries, age criteria
must be as per local regulations; eg, subjects in Canada must be aged =
18 years or =19 years of age at Screening, as per the applicable
Canadian provincial criteria.
3. Diagnosis of primary HTN for at least 6 months prior to Screening and:
• Currently treated with 2 antihypertensive classes of drug (difficult-totreat subjects), or currently treated with at least 3 antihypertensive
classes of drug including a diuretic (treatment resistant subjects), at the
MTDs of those medications (ie, the subject can tolerate the current dose
of each medication but higher doses have caused or may worsen side
effects), with no change in their antihypertensive regimen (drug, dose,
or schedule) for at least 6 weeks, and with medication adherence =80%
during the Run in Period.
• Have a systolic AOBP between 140 mmHg and 179 mmHg (inclusive) at
Screening (Visit 1) while on their current chronic antihypertensive
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treatments.
• Have a successful ABPM measurement with a mean systolic daytime
ABP >135 mmHg after the Run-in Period while on their current chronic
antihypertensive treatments. An ABPM is successful if at least 21
daytime readings and 6 nighttime readings have been successfully
recorded.
4. Women of childbearing potential and nonsurgically sterile male
subjects who are sexually active must agree to use an approved highly
effective form of contraception from the time of informed consent until
30 days post-dose. Approved forms of contraception include intrauterine
devices, intrauterine hormone-releasing systems, bilateral tubal ligation,
or hormonal contraceptives (oral birth control pills, depo, patch, or
injectable) together with supplementary method such as condoms or
diaphragms with spermicidal gel or foam.
5. Women of childbearing potential must have a negative serum
pregnancy test result at Screening and a negative urine pregnancy test
result at the Inclusion Visit (Visit 2B, Day 1).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 500

Exclusion Criteria

1. Known or suspected secondary HTN (eg, hyperaldosteronism, renovascular HTN, pheochromocytoma, Cushing’s disease).
2. Systolic AOBP =180 mmHg or DBP =110 mmHg at the Screening or Inclusion Visit (Visit 2B, Day 1) and confirmed by a second measurement within 30 minutes to 1 hour.
3. Known hypertensive retinopathy (Keith-Wagener Grade 3 or Grade 4) and/or hypertensive encephalopathy.
4. Upper arm circumference that is outside the limits of the study-provided BP cuff associated with either the ABPM and/or AOBP measurement device.
5. History of spontaneous or drug-induced angioedema.
6. History of any drug-related allergy or hypersensitivity to any components of the IP (firibastat [QGC001] or placebo).
7. Known severe aortic stenosis (symptomatic or asymptomatic with valvular indexed surface <0.5 cm²/m²).
8. Subjects with severe symptomatic heart failure (New York Heart Association [NYHA] Class III or Class IV).
9. History of acute coronary syndrome (non-ST elevation myocardial infarction [MI], ST elevation MI, and unstable angina pectoris), stroke, or transient ischemic attack within 6 months prior to Visit 2A, Day 0.
10. Known history of malabsorption syndrome, or has undergone gastrointestinal surgery, including bariatric procedures that induce chronic malabsorption, within 2 years of Screening.
11. Treatment with anti-obesity drugs or procedures 3 months prior to Screening (ie, surgery, aggressive diet regimen, etc.), leading to unstable body weight.
12. Female who is breastfeeding, pregnant, or planning to become pregnant during the study period.
13. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 3 years.
14. Shift workers who routinely sleep during the daytime and/or whose work hours include midnight.
15. Subjects with moderate to severe hepatic impairment (Child-Pugh A, B, or C); alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) >3×upper limit of normal (ULN), or a total bilirubin =1.5×ULN (unless secondary to Gilbert’s syndrome), or direct bilirubin >ULN in subjects with Gilbert’s syndrome at Screening.
16. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (Levey AS, et al. 2009) at Screening.
17. History of any blood disorder, other than sickle cell trait, causing hemolysis or unstable red blood cells (eg, malaria, babesiosis, hemolytic anemia, thalassemia, sickle cell anemia).
18. Subjects with documented DI.
19. Subjects with Type 1 diabetes mellitus.
20. Subjects with Type 2 diabetes mellitus who:
• Are poorly controlled, defined as glycosylated hemoglobin A1c (HbA1c) >9% at Screening; OR
• Are taking short-acting insulin. Use of a stable dose [=12 weeks prior to Screening] of the following medications, (or any combination of the following medications) is permitted: glucagon like peptide 1 analog, metformin, sulfonylurea, dipeptidyl peptidase-4 inhibitor, and single basal insulin, sodium glucose co-transporter 2 (SGLT2) inhibitors and pioglitazone.
21. Routine or anticipated treatment with any systemic corticosteroid. Use of topical, inhaled, intra articular or nasal corticosteroids is permitted.
22. Clinical evidence of thyroid disease, thyroid hormone therapy that is not stable =4 weeks prior to Screening, or a thyroid-stimulating hormone (TSH) level <0.75×lower limit of normal or >1.5×ULN at Screening.
23. History of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the effects of firibastat (QGC001) administered at 1000 mg orally (po) once daily (QD) on blood pressure (BP) over 12 weeks;Secondary Objective: • To assess the safety of firibastat (QGC001) administered at 1000 mg po QD over 24 weeks and 48 weeks<br>• To assess change in BP over time<br>in subjects with uncontrolled primary HTN who have been treated with at least 2 classes of antihypertensive therapies at the maximum tolerated doses (MTDs) (ie, difficult-to-treat or treatment resistant patients) ;Primary end point(s): The primary efficacy endpoint is the change from baseline in systolic AOBP at Week 12.;Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): AOBP at every visit.<br>24-hour ambulatory BP monitoring (ABPM) assessed at baseline and<br>after 12 weeks (end of double-blind period [Period 1]).<br>Biomarkers NT-ProBNP, fibrinogen and hsCRP at Visit 2B, Day 1 and Visit<br>4B, Day 85 (±3 d).<br>Proportion of subjects requiring an increase in the dose of current<br>antihypertensive drugs or addition of another hypertensive drug during<br>the open-label treatment periods (Periods 2 and 3) of the study.;Timepoint(s) of evaluation of this end point: AOBP at every visit.<br>24-hour ambulatory BP at baseline and after 12 weeks.<br>Biomarkers NT-ProBNP fibrinogen and hsCRP at Visit 2B, Day 1, and<br>Visit 4B, Day 85 (±3 d).