Randomized Study of Extended Treatment With Firibastat in Treatment-Resistant Hypertension (REFRESH)

NCT04857840 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: QGC001-3QG2
• Study Type: interventional
• Target: 419
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a double-blind, placebo-controlled and open-label, multicenter efficacy and long-term safety study of firibastat (QGC001) 1000 mg (2×500 mg tablets) administered po, QD, for up to 48 weeks in patients with difficult-to-treat/treatment-resistant HTN. Subjects will continue to take their chronic antihypertensive therapies (at least 2 classes of antihypertensive therapies) at the MTDs during the Run in Period and for the duration of the study. For treatment-resistant subjects, one of the antihypertensive therapies must be a diuretic; for difficult-to-treat subjects, the antihypertensive therapies do not have to include a diuretic. Subjects will complete subject medication diaries during the Run-in Period. If systolic automated office BP (AOBP) is ≥180 mmHg or diastolic BP (DBP) ≥110 mmHg at any visit during the study (and repeated and confirmed within 30 min), the subject will be withdrawn from the study and will receive appropriate treatment.

Conditions

Hypertension (HTN)

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint is the change from baseline in systolic AOBP at Week 12.

  The main criterion will be analyzed with a mixed model with repeated measures (MMRM) at Week 6 (Day 42) and Week 12 (Day 84), with an unstructured matrix of covariance.

  12 weeks

Study Arms (2)

Arm A: Investigational Product /Period 1,2 and 3 if any (open label)

EXPERIMENTAL

Firibastat 1000 mg tablets QD - 12 weeks

Drug: Firibastat (QGC001) Period 1

Arm B: Placebo/Period1 only

PLACEBO COMPARATOR

Placebo tablets QD 12 weeks in Period 1 only, followed by open label Period 2 and 3 if any.

Drug: Firibastat (QGC001) Period 1

Interventions

Firibastat (QGC001) Period 1 DRUG

1000 mg (2 x 500 mg) tablets QD per Os

Also known as: Firibastat (QGC001) Open label

Arm A: Investigational Product /Period 1,2 and 3 if any (open label); Arm B: Placebo/Period1 only

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and willing to provide written informed consent, and able to comply with the study procedures and restrictions.
• Adult men and women (at Screening).
• Diagnosis of primary HTN for at least 6 months prior to Screening and:
• Currently treated with 2 antihypertensive classes of drug (difficult-to-treat 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 while on their current chronic antihypertensive 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.
• 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 hormonal intrauterine devices, hormonal contraceptives (oral birth control pills, depo, patch, or injectable) together with supplementary barrier methods such as condoms or diaphragms with spermicidal gel or foam.

You may not qualify if:

• Target population:
• Subjects with uncontrolled primary HTN despite being treated with at least 2 classes of antihypertensive therapies, at the MTDs (difficult-to-treat or treatment-resistant patients).
• Subjects who meet all of the following criteria will be eligible to participate in the study:
• Able to understand and willing to provide written informed consent, and able to comply with the study procedures and restrictions.
• Adult men and women (at Screening).
• Diagnosis of primary HTN for at least 6 months prior to Screening and:
• Currently treated with 2 antihypertensive classes of drug (difficult-to-treat 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 while on their current chronic antihypertensive 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.
• 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 hormonal intrauterine devices, hormonal contraceptives (oral birth control pills, depo, patch, or injectable) together with supplementary barrier methods such as condoms or diaphragms with spermicidal gel or foam.
• Subjects who meet any of the following criteria will be excluded from participation in the study:
• Known or suspected secondary HTN (eg, hyperaldosteronism, renovascular HTN, pheochromocytoma, Cushing's disease).
• Known hypertensive retinopathy (Keith-Wagener Grade 3 or Grade 4) and/or hypertensive encephalopathy.
• Upper arm circumference that is outside the limits of the study-provided BP cuff associated with either the ABPM and/or AOBP measurement device.
• History of spontaneous or drug-induced angioedema.

Sponsors & Collaborators

• Quantum Genomics SA: lead
• PRA Health Sciences: collaborator

Study Sites (2)

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

Canadian Phase Onward

Toronto, Ontario, M3J 0K2, Canada

Location

MeSH Terms

Conditions

Hypertension

Interventions

firibastat

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Georges GB BAKRIS, MD

  AHA Comprehensive Hypertension Center University of Chicago Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Random allocation of the double blinded 2 Arms : Double-blind placebo controlled during Period 1 of 12 weeks
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2 Arms : Double-blind placebo controlled during Period 1 of 12 weeks followed by open-label periods 2 (24 weeks) and 3 (12 weeks)

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: April 23, 2021
• Study Start: August 5, 2021
• Primary Completion: January 9, 2023
• Study Completion: January 9, 2023
• Last Updated: January 17, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CA (1)