Chronic Kidney Diseases
Conditions
Keywords
Stage 3b/4 chronic kidney disease, Hypertension, Uncontrolled Hypertension, Blood pressure, Mineralocorticoid Receptor Antagonist, Randomized withdrawal
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.
Detailed description
Participants in this study will be recruited, screened, and enrolled at approximately 140 study sites globally. The study will consist of the following periods: 1. Pretreatment Phase: This will include prescreening assessment and screening period of up to 4 weeks and 2-week Open-label placebo Run-In period. 2. A 24-week Double-blind Treatment Period (Randomization to Week 24) will include: An initial 12-week (Randomization to Week 12) and second 12-week (Week 12 to Week 24) treatment period and a second 12-week treatment period (Week 12 to Week 24), during both the periods study drug will be titrated. 3. A 24-week Open-label Treatment Period (Week 24 to Week 48) during which eligible participants will receive Open-label KBP-5074. 4. A 4-week Randomized Double-blind Withdrawal Period (Week 48 to Week 52) during which eligible participants will be randomized to continue their current KBP-5074 dose at the end of Open-label treatment or receive matching placebo for 4 weeks. 5. A 4-week post-treatment Follow-Up Period (Week 52 to Week 56). During, 24-week Double-blind Treatment Period, 24-week Open-label Treatment Period, and at 4-week Randomized Double-blind Withdrawal Period, the background antihypertensive medications change may or may not be allowed. At Double-blind Treatment Period, eligible participants will be randomly assigned in a 1:1 ratio to KBP-5074 0.25 mg or matching placebo once daily (QD). At the Randomized Double-blind Withdrawal Period, participants who meet the randomized withdrawal criteria will be randomly assigned in a 1:1 ratio to continue their current KBP-5074 dose at the end of the Open-label Treatment Period or matching placebo QD.
Interventions
DRUGPlacebo
Participants will orally receive placebo matching to KBP-5074 tablets QD.
DRUGKBP-5074
Participants will orally receive KBP-5074 tablets, from 0.25 mg to a maximum dose of 0.5-mg QD.
Sponsors
KBP Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All individuals directly involved in the conduct of the study, including participants, Investigators, site staff, clinical research organization (CRO) personnel, and Sponsor study personnel, will remain blinded to treatment assignments until all participants have completed the Week 56 end of study (EOS) Visit (Visit 17) and the database locked in preparation.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in seated trough cuff SBP from baseline to Week 12 | From baseline to Week 12 | Efficacy of KBP-5074 in reducing SBP by assessing change in seated trough cuff SBP for KBP-5074 dose regimen compared to placebo, will be evaluated. |
| Change in seated trough cuff SBP from Week 48 to Week 52 | Week 48 to Week 52 | Durability of KBP-5074 in reducing SBP by assessing change in seated trough cuff SBP for the KBP-5074 dose regimen compared to placebo, will be evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in seated trough cuff SBP and DBP from baseline to Week 48 | From baseline to Week 48 | Effect of KBP-5074 on SBP and DBP by assessing change in seated trough cuff SBP and DBP, will be evaluated. |
| Changes in urinary albumin: creatinine ratio (UACR) from baseline to Week 12 and Week 24 for participants with UACR ≥30 mg/g at baseline | From baseline to Week 12 and Week 24 | Effect of KBP-5074 on UACR by assessing changes in UACR for participants with UACR ≥30 mg/g at baseline, will be evaluated. |
| Percentage changes in UACR from baseline to Week 12 and Week 24 for participants with UACR ≥30 mg/g at baseline | From baseline to Week 12 and Week 24 | Effect of KBP-5074 on UACR by assessing percentage changes in UACR for participants with UACR ≥30 mg/g at baseline, will be evaluated. |
| Changes in UACR from baseline to Week 12, Week 24, and Week 48 | From baseline to Week 12, Week 24, and Week 48 | Effect of KBP-5074 on UACR by assessing changes in UACR for participants with macroalbuminuria (defined as UACR ≥300 mg/g) and microalbuminuria (defined as UACR ≥30 and \<300 mg/g) at baseline, will be evaluated. |
| Change in seated trough cuff SBP from baseline to Week 24 | From baseline to Week 24 | Efficacy and durability of KBP-5074 in reducing SBP by assessing change in seated trough cuff SBP, will be evaluated. |
| Change in seated trough cuff DBP from Week 48 to Week 52 | Week 48 to Week 52 | Effect of KBP-5074 on DBP by assessing change in seated trough cuff DBP, will be evaluated. |
| Change in UACR from Week 48 to Week 52 | Week 48 to Week 52 | Effect of KBP-5074 on UACR by assessing changes in UACR for participants with UACR ≥30 mg/g, macroalbuminuria (defined as UACR ≥300 mg/g) and microalbuminuria (defined as UACR ≥30 and \<300 mg/g) at baseline, will be evaluated. |
| Percentage change in UACR from Week 48 to Week 52 | Week 48 to Week 52 | Effect of KBP-5074 on UACR by assessing percentage changes in UACR for participants with UACR ≥30 mg/g, macroalbuminuria (defined as UACR ≥300 mg/g) and microalbuminuria (defined as UACR ≥30 and \<300 mg/g) at baseline, will be evaluated. |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | Screening (Week -6 to -2) until EOS (Week 56) or Unscheduled visit or end of treatment or early termination | The safety and tolerability of KBP-5074,will be evaluated. |
| Percentage changes in UACR from baseline to Week 12, Week 24, and Week 48 | From baseline to Week 12, Week 24, and Week 48 | Effect of KBP-5074 on UACR by assessing percentage changes in UACR for participants with macroalbuminuria (defined as UACR ≥300 mg/g) and microalbuminuria (defined as UACR ≥30 and \<300 mg/g) at baseline, will be evaluated. |
| Changes in seated trough cuff diastolic blood pressure (DBP) from baseline to Week 12 and Week 24 | From baseline to Week 12 and Week 24 | Effect of KBP-5074 on DBP by assessing change in seated trough cuff DBP, will be evaluated. |
Countries
Australia, Bosnia and Herzegovina, Bulgaria, Canada, China, Croatia, Czechia, Georgia, Germany, Hong Kong, Hungary, Israel, Latvia, Lithuania, Malaysia, Poland, Serbia, South Africa, South Korea, Spain, Taiwan, United States
Outcome results
None listed