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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04968184




Registration number
NCT04968184
Ethics application status
Date submitted
7/07/2021
Date registered
20/07/2021
Date last updated
13/08/2024

Titles & IDs
Public title
Efficacy and Safety of KBP-5074 in Uncontrolled Hypertension and Moderate or Severe Chronic Kidney Disease (CKD)
Scientific title
A Phase 3 Randomized Double-Blind Placebo-Controlled Multicenter Study to Assess the Efficacy and Safety of KBP-5074 Mineralocorticoid Receptor Antagonist in Subjects With Uncontrolled Hypertension and Moderate or Severe (Stage 3b/4) CKD
Secondary ID [1] 0 0
KBP5074-3-001
Universal Trial Number (UTN)
Trial acronym
Clarion-CKD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Kidney Diseases 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - KBP-5074

Placebo comparator: Placebo - Open-label Placebo Run-In Period: All eligible participants will receive matching placebo, for approximately 2 weeks, during the Open-label placebo Run-In period.

Double-blind Treatment Period: All eligible participants will receive matching placebo, from week 2 thru week 24 during the Double-blind treatment Period

Open-label Treatment Period: All eligible participants will receive KBP-5074, from week 24 thru week 48 during the Open label Treatment Period

Randomized Double-blind Withdrawal Period: All eligible participants will be randomized to either continue their current KBP-5074 dose at the end of the Open-Label Treatment Period or receive matching placebo from week 48 thru week 52.

Follow up Period: All participants will discontinue matching placebo/KBP-5074 and be followed for safety until end of study visit from week 52 to week 56.

Experimental: KBP-5074 - Open-label Placebo Run-In period: All eligible participants will receive matching placebo, for approximately 2 weeks during the Open-label placebo Run-In period.

Double-blind Treatment Period: All eligible participants will receive KBP-5074, from week 2 thru week 24 during the Double-blind Treatment Period

Open-label Treatment Period: All eligible participants will receive KBP-5074, from week 24 thru week 48 during the Open label Treatment Period

Randomized Double-blind Withdrawal Period: All eligible participants will be randomized to either continue their current KBP-5074 dose at the end of the Open-Label Treatment Period or receive matching placebo from week 48 thru week 52.

Follow up Period: All participants will discontinue matching placebo/KBP-5074 and be followed for safety until end of study visit from week 52 to week 56.


Treatment: Drugs: Placebo
Participants will orally receive placebo matching to KBP-5074 tablets QD.

Treatment: Drugs: KBP-5074
Participants will orally receive KBP-5074 tablets, from 0.25 mg to a maximum dose of 0.5-mg QD.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in seated trough cuff SBP from baseline to Week 12
Timepoint [1] 0 0
From baseline to Week 12
Primary outcome [2] 0 0
Change in seated trough cuff SBP from Week 48 to Week 52
Timepoint [2] 0 0
Week 48 to Week 52
Secondary outcome [1] 0 0
Change in seated trough cuff SBP from baseline to Week 24
Timepoint [1] 0 0
From baseline to Week 24
Secondary outcome [2] 0 0
Changes in seated trough cuff diastolic blood pressure (DBP) from baseline to Week 12 and Week 24
Timepoint [2] 0 0
From baseline to Week 12 and Week 24
Secondary outcome [3] 0 0
Changes in seated trough cuff SBP and DBP from baseline to Week 48
Timepoint [3] 0 0
From baseline to Week 48
Secondary outcome [4] 0 0
Changes in urinary albumin: creatinine ratio (UACR) from baseline to Week 12 and Week 24 for participants with UACR =30 mg/g at baseline
Timepoint [4] 0 0
From baseline to Week 12 and Week 24
Secondary outcome [5] 0 0
Percentage changes in UACR from baseline to Week 12 and Week 24 for participants with UACR =30 mg/g at baseline
Timepoint [5] 0 0
From baseline to Week 12 and Week 24
Secondary outcome [6] 0 0
Changes in UACR from baseline to Week 12, Week 24, and Week 48
Timepoint [6] 0 0
From baseline to Week 12, Week 24, and Week 48
Secondary outcome [7] 0 0
Percentage changes in UACR from baseline to Week 12, Week 24, and Week 48
Timepoint [7] 0 0
From baseline to Week 12, Week 24, and Week 48
Secondary outcome [8] 0 0
Change in seated trough cuff DBP from Week 48 to Week 52
Timepoint [8] 0 0
Week 48 to Week 52
Secondary outcome [9] 0 0
Change in UACR from Week 48 to Week 52
Timepoint [9] 0 0
Week 48 to Week 52
Secondary outcome [10] 0 0
Percentage change in UACR from Week 48 to Week 52
Timepoint [10] 0 0
Week 48 to Week 52
Secondary outcome [11] 0 0
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Timepoint [11] 0 0
Screening (Week -6 to -2) until EOS (Week 56) or Unscheduled visit or end of treatment or early termination

Eligibility
Key inclusion criteria
* Body mass index (BMI) must be =19 to <45 kg/m^2 at the Screening Visit
* Participant must have uncontrolled hypertension defined as meeting both of the following criteria:

* The participant has a resting seated trough cuff SBP =140 mm Hg at the Screening Visit (Visit 1), and at the start (Visit 2) and end (Visit 3) of the Run-In Period
* The participant is taking 2 or more antihypertensive medications that have been titrated upward as tolerated to hypertension target doses per local SoC and have been stable (i.e., without any dose adjustments) from 4 weeks before the Screening Visit (Visit 1) through the end of the Run-In Period (Visit 3)
* The participant must have Stage 3b (eGFR [EPI] =30 and =44 mL/min/1.73 m^2) or Stage 4 (eGFR [EPI] =15 and <30 mL/min/1.73 m^2) CKD.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has a resting seated trough cuff SBP =180 mm Hg at the Screening Visit (Visit 1) or at the start (Visit 2) or end (Visit 3) of the Run-In Period
* Participant has a serum potassium level >4.8 mmol/L during the Screening or Run-In Periods
* Participant has had a serum potassium level >5.6 mmol/L within 2 weeks before the Screening Visit (Visit 1)
* Participant has been hospitalized for hyperkalemia within the 3 months before the Randomization Visit (Visit 3)
* Participant was not compliant with taking placebo during the Run-in Period or participant was not compliant with background antihypertensive medications during the Run-in Period as assessed at the Randomization Visit (Visit 3)
* Participant has taken an mineralocorticoid receptor antagonist (MRA), a potassium-sparing diuretic, or chronic potassium supplements during the 4 weeks before the Screening Visit (Visit 1)
* Participant has taken potassium binders for the treatment of hyperkalemia during the 3 months before the Screening Visit (Visit 1)
* Participant has taken a strong cytochrome P450 (CYP) CYP3A4 inducer or strong CYP3A4 inhibitor during the 7 days before the Randomization Visit (Visit 3)
* Participant has taken a prohibited traditional Chinese medication during the 28 days prior to Screening Visit (Visit 1).
* Participant was administered any other investigational product within 4 weeks or 5 half-lives (whichever is longer) prior to the Screening Visit (Visit 1).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/07/2024
Sample size
Target
Accrual to date
Final
652
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Renal Research - Gosford
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Connecticut
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Massachusetts
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Minnesota
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Missouri
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Nevada
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New York
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North Carolina
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Ohio
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Bosnia and Herzegovina
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Kanton Sarajevo
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Sofia
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Croatia
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Kvemo Kartli
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Shida Kartli
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Riga
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Perak
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Malaysia
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Wilayah Persekutuan Kuala Lumpur
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Kujawsko-pomorskie
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Katowice
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Lodz
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Lublin
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Poznan
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Warszawa
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Wroclaw
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Serbia
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Belgrade
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Serbia
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Nišavski Okrug
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Serbia
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Vojvodina
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Serbia
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Kragujevac
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South Africa
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Free State
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South Africa
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Gauteng
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South Africa
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Kwazulu-Natal
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South Africa
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Western Cape
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Spain
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Lugo
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Spain
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Valenciana, Comunidad
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Spain
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Barcelona
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Granada
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Madrid
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Spain
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Valencia
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Taiwan
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Taichung Municipality
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Taiwan
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Taipei Special Muncipality
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Taiwan
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Taichung
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Taiwan
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Taipei
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Taiwan
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Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
KBP Biosciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase 3, randomized, Double-blind, placebo-controlled, 2-arm, parallel-group, multicenter study with randomized withdrawal will evaluate the efficacy, safety, and durability of KBP-5074 in adult participants who have stage 3b/4 chronic kidney disease (CKD) (estimated glomerular filtration rate \[eGFR\] calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula \[eGFR {EPI}\] =15 to =44 mL/min/1.73 m\^2) and uncontrolled hypertension (systolic blood pressure (SBP) =140 and \<180 mm Hg and taking 2 or more antihypertensive medications.
Trial website
https://clinicaltrials.gov/study/NCT04968184
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04968184