Efficacy and Safety of KBP-5074 in Uncontrolled Hypertension and Moderate or Severe Chronic Kidney Disease (CKD)

Phase 3

Terminated

Conditions: Chronic Kidney Diseases

Interventions: Drug: Placebo
Drug: KBP-5074

Registration Number: NCT04968184

Lead Sponsor: KBP Biosciences

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 652

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
KBP-5074	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.
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 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.
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.

Trial Locations

Locations (211): G & L Research, LLC
🇺🇸
Foley, Alabama, United States
Apogee Clinical Research, LLC
🇺🇸
Huntsville, Alabama, United States
Aventiv Research, Inc
🇺🇸
Mesa, Arizona, United States
National Heart Institute
🇺🇸
Beverly Hills, California, United States
Amicis Research Center (Valencia)
🇺🇸
Granada Hills, California, United States
Amicis Research Center
🇺🇸
Lancaster, California, United States
Renal Consultants Medical Group - Granada Hills
🇺🇸
Northridge, California, United States
United Clinical Research and Innovations
🇺🇸
South Gate, California, United States
Solano Kidney Care
🇺🇸
Vacaville, California, United States
Desert Cities Dialysis - Amethyst
🇺🇸
Victorville, California, United States
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G & L Research, LLC
🇺🇸Foley, Alabama, United States