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

KBP Biosciences

Status and phase: Terminated; Phase 3

Conditions: Chronic Kidney Diseases

Treatments: Drug: Placebo; Drug: KBP-5074

Study type: Interventional

Funder types: Industry

Identifiers

NCT04968184

KBP5074-3-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 652 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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652 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

KBP-5074

Experimental group

Description:

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:

Drug: KBP-5074