Ignite Creation Date:
2024-05-06 @ 4:03 PM
Last Modification Date:
2024-10-26 @ 2:03 PM
Study NCT ID:
NCT04857840
Status:
TERMINATED
Last Update Posted:
2023-01-17
First Post:
2021-04-20
Brief Title:
Randomized Study of Extended Treatment With Firibastat in Treatment-Resistant Hypertension REFRESH
Sponsor:
Quantum Genomics SA
Organization:
Quantum Genomics SA
Study Overview
Official Title:
A Phase 3 Double-blind Placebo-controlled and Open-label Efficacy and Long-term Safety Study of Firibastat QGC001 Administered Orally Once Daily for Up to 48 Weeks in Patients With Difficult-to-treatResistant Hypertension
Status:
TERMINATED
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
No Efficacy demonstrated inn the QGC001-3QG1 study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
REFRESH
Brief Summary:
This is a double-blind placebo-controlled and open-label multicenter efficacy and long-term safety study of firibastat QGC001 1000 mg 2500 mg tablets administered po QD for up to 48 weeks in patients with difficult-to-treattreatment-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or diastolic BP DBP 110 mmHg at any visit during the study and repeated and confirmed within 30 min the subject will be withdrawn from the study and will receive appropriate treatment
Detailed Description:
For each subject the study will include a Screening Visit a Run-in Period an Inclusion Visit Visit 2A Day 0 and Visit 2B Day 1 and up to 3 study treatment periods with clinic visits and safety phone calls
Screening assessments will be performed at Visit 1 Day -28 Eligible subjects will then enter the Run-in Period during which medication adherence will be assessed via a medication diary The duration of the Run in Period will be no less than 28 days and no more than 33 days this time period allows for 2 repeat ambulatory BP monitoring ABPM recordings at Visit 2A if required
Subjects who meet the inclusionexclusion criteria at the end of the Run in Period will be randomly assigned to either Group A or Group B A total of 200 subjects 100 in Group A and 100 in Group B will be randomized to continue treatment with firibastat QGC001 during Period 3 Subjects will receive either double-blind firibastat QGC001 or placebo for the first 12-week study treatment period Period 1 followed by open label treatment with firibastat for 24 weeks Period 2 or 36-weeks Period 2 plus an additional 12-weeks of open-label treatment in Period 3
At Visit 2A Day 0 an ABPM device will be installed for each subject who has successfully completed the Run-in Period with a medication adherence 80 and remains eligible to participate in the study The ABPM device will be set to record for at least 24 hours with the measurement frequency set at 30-minute intervals during the day 800 am to 1000 pm theoretically 28 readings 2 per hour and 60-minute intervals at night 1000 pm to 800 am theoretically 10 readings 1 per hour Subjects must have a successful ABPM measurement prior to being randomized and starting treatment with investigational product IP at Visit 2B Day 1 An ABPM recording is considered successful if at least 21 daytime readings and 6 nighttime readings have been successfully recorded A duration of less than 24 hours eg 23 hours and 30 minutes would be acceptable for a successful ABPM recording providing it successfully confirms 21 daytime readings and 6 nighttime readings If the ABPM recording is not successful 2 further attempts are permitted
Following a successful ABPM recording assessed at Visit 2B Day 1 subjects who still meet the inclusionexclusion criteria and who have a mean daytime systolic ambulatory blood pressure ABP 135 mmHg will undergo visit-specific assessments and will be randomized to Group A or Group B and receive either firibastat QGC001 or placebo for the 12-week double-blind treatment period Period 1 followed by open label firibastat for 24 weeks Period 2 or 36 weeks Period 2 plus Period 3 200 subjects in addition to their current chronic antihypertensive treatments
During Period 1 the investigator or designee will call subjects by telephone on Day 14 3 d to collect any potential adverse events AEs check IP compliance and record any concomitant medications Subjects will receive a second safety phone call during Period 2 at Day 98 3 d
Subjects will attend the study site for the following study visits
Period 1 Visit 2A Day 0 Visit 2B Day 1 Visit 3 Day 42 3 d Visit 4A Day 84 3 d and Visit 4B Day 85 3 d
Period 2 Visit 5 Day 126 3 d Visit 6 Day 168 3 d Visit 7 Day 252 3 d and Visit 8 Day 280 3 d
Period 3Visit 9 Day 336 3 d and Visit 10 Day 364 3 d On completion of their final study treatment period subjects will attend an End of Treatment EOT Visit A safety follow-up will be performed at the End of Study EOS Visit
For subjects who stop study treatment at the end of Period 2 the EOT Visit will be at Visit 7 Day 252 3 d and the EOS Visit will be Visit 8 Day 280 3 d
Subjects who continue study treatment into Period 3 will not attend Visit 8 Day 280 3 d Subjects who stop treatment with firibastat QGC001 after Period 3 will attend an EOT Visit at Visit 9 Day 336 3 d and an EOS Visit at Visit 10 Day 364 3 d
Subjects who discontinue the study early should undergo an Early Termination Visit and an EOS visit 28 days 3 d after the last dose of IP except in the case of consent withdrawal
Each subject will be assigned to one of 5 pharmacokinetic PK subgroups 50 subjects at selected sites will undergo an enhanced PK sampling schedule 6 PK samples will be collected according to the PK subgroup sampling schedule and 700 subjects will be assigned to the standard PK sampling schedule 2 PK samples will be collected according to the PK subgroup sampling schedule
At each study visit AOBP orthostatic BP and heart rate HR will be measured and other visit-specific procedures will be performed including electrocardiograms ECGs clinical laboratory evaluations clinical examinations collection of blood for PK samples and the biomarker N terminal pro-B-type natriuretic peptide NT-ProBNP and monitoring of AEs and concomitant medications At the EOS Visit safety follow-up assessments will include clinical examination AOBP orthostatic BP ECG HR and clinical laboratory assessments AE monitoring and concomitant medications
Allergic skin reactions andor diabetes insipidus DI are considered adverse events of special interest AESIs with immediate notification during the study treatment period
Screening assessments will be performed at Visit 1 Day -28 Eligible subjects will then enter the Run-in Period during which medication adherence will be assessed via a medication diary The duration of the Run in Period will be no less than 28 days and no more than 33 days this time period allows for 2 repeat ambulatory BP monitoring ABPM recordings at Visit 2A if required
Subjects who meet the inclusionexclusion criteria at the end of the Run in Period will be randomly assigned to either Group A or Group B A total of 200 subjects 100 in Group A and 100 in Group B will be randomized to continue treatment with firibastat QGC001 during Period 3 Subjects will receive either double-blind firibastat QGC001 or placebo for the first 12-week study treatment period Period 1 followed by open label treatment with firibastat for 24 weeks Period 2 or 36-weeks Period 2 plus an additional 12-weeks of open-label treatment in Period 3
At Visit 2A Day 0 an ABPM device will be installed for each subject who has successfully completed the Run-in Period with a medication adherence 80 and remains eligible to participate in the study The ABPM device will be set to record for at least 24 hours with the measurement frequency set at 30-minute intervals during the day 800 am to 1000 pm theoretically 28 readings 2 per hour and 60-minute intervals at night 1000 pm to 800 am theoretically 10 readings 1 per hour Subjects must have a successful ABPM measurement prior to being randomized and starting treatment with investigational product IP at Visit 2B Day 1 An ABPM recording is considered successful if at least 21 daytime readings and 6 nighttime readings have been successfully recorded A duration of less than 24 hours eg 23 hours and 30 minutes would be acceptable for a successful ABPM recording providing it successfully confirms 21 daytime readings and 6 nighttime readings If the ABPM recording is not successful 2 further attempts are permitted
Following a successful ABPM recording assessed at Visit 2B Day 1 subjects who still meet the inclusionexclusion criteria and who have a mean daytime systolic ambulatory blood pressure ABP 135 mmHg will undergo visit-specific assessments and will be randomized to Group A or Group B and receive either firibastat QGC001 or placebo for the 12-week double-blind treatment period Period 1 followed by open label firibastat for 24 weeks Period 2 or 36 weeks Period 2 plus Period 3 200 subjects in addition to their current chronic antihypertensive treatments
During Period 1 the investigator or designee will call subjects by telephone on Day 14 3 d to collect any potential adverse events AEs check IP compliance and record any concomitant medications Subjects will receive a second safety phone call during Period 2 at Day 98 3 d
Subjects will attend the study site for the following study visits
Period 1 Visit 2A Day 0 Visit 2B Day 1 Visit 3 Day 42 3 d Visit 4A Day 84 3 d and Visit 4B Day 85 3 d
Period 2 Visit 5 Day 126 3 d Visit 6 Day 168 3 d Visit 7 Day 252 3 d and Visit 8 Day 280 3 d
Period 3Visit 9 Day 336 3 d and Visit 10 Day 364 3 d On completion of their final study treatment period subjects will attend an End of Treatment EOT Visit A safety follow-up will be performed at the End of Study EOS Visit
For subjects who stop study treatment at the end of Period 2 the EOT Visit will be at Visit 7 Day 252 3 d and the EOS Visit will be Visit 8 Day 280 3 d
Subjects who continue study treatment into Period 3 will not attend Visit 8 Day 280 3 d Subjects who stop treatment with firibastat QGC001 after Period 3 will attend an EOT Visit at Visit 9 Day 336 3 d and an EOS Visit at Visit 10 Day 364 3 d
Subjects who discontinue the study early should undergo an Early Termination Visit and an EOS visit 28 days 3 d after the last dose of IP except in the case of consent withdrawal
Each subject will be assigned to one of 5 pharmacokinetic PK subgroups 50 subjects at selected sites will undergo an enhanced PK sampling schedule 6 PK samples will be collected according to the PK subgroup sampling schedule and 700 subjects will be assigned to the standard PK sampling schedule 2 PK samples will be collected according to the PK subgroup sampling schedule
At each study visit AOBP orthostatic BP and heart rate HR will be measured and other visit-specific procedures will be performed including electrocardiograms ECGs clinical laboratory evaluations clinical examinations collection of blood for PK samples and the biomarker N terminal pro-B-type natriuretic peptide NT-ProBNP and monitoring of AEs and concomitant medications At the EOS Visit safety follow-up assessments will include clinical examination AOBP orthostatic BP ECG HR and clinical laboratory assessments AE monitoring and concomitant medications
Allergic skin reactions andor diabetes insipidus DI are considered adverse events of special interest AESIs with immediate notification during the study treatment period
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None