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.
Brief Title
Efficacy and Safety of KBP-5074 in Uncontrolled Hypertension and Moderate or Severe Chronic Kidney Disease (CKD)
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.
The study design included a pre-planned futility determination by an Independent Data Monitoring Committee (IDMC).
The trial was originally sponsored by KBP Biosciences PTE Ltd, but sponsorship was transferred to Novo Nordisk after the trial was terminated following the futility determination by IDMC.
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.
The study design included a pre-planned futility determination by an Independent Data Monitoring Committee (IDMC).
The trial was originally sponsored by KBP Biosciences PTE Ltd, but sponsorship was transferred to Novo Nordisk after the trial was terminated following the futility determination by IDMC.
Completion Date
Completion Date Type
Actual
Conditions
CHRONIC KIDNEY DISEASES
Eligibility Criteria
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).
* 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).
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Stage 3b/4 chronic kidney disease
Hypertension
Uncontrolled Hypertension
Blood pressure
Mineralocorticoid Receptor Antagonist
Randomized withdrawal
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04968184
Org Class
Industry
Org Full Name
Novo Nordisk A/S
Org Study Id
KBP5074-3-001
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official 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
Primary Outcomes
Outcome Description
Efficacy of KBP-5074 in reducing SBP by assessing change in seated trough cuff SBP for KBP-5074 dose regimen compared to placebo, was evaluated.
Outcome Measure
Change in Seated Trough Cuff Systolic Blood Pressure (SBP) From Baseline to Week 12
Outcome Time Frame
From baseline to Week 12
Outcome Description
Durability of KBP-5074 in reducing SBP by assessing change in seated trough cuff SBP for the KBP-5074 dose regimen compared to placebo, was evaluated.
Outcome Measure
Change in Seated Trough Cuff SBP From Week 48 to Week 52
Outcome Time Frame
From Week 48 to Week 52
Secondary Ids
Secondary Id
2021-003636-88
Secondary Outcomes
Outcome Description
Efficacy and durability of KBP-5074 in reducing SBP by assessing change in seated trough cuff SBP, were evaluated.
Outcome Time Frame
From baseline to Week 24
Outcome Measure
Change in Seated Trough Cuff SBP From Baseline to Week 24
Outcome Description
Effect of KBP-5074 on DBP by assessing change in seated trough cuff DBP, was evaluated.
Outcome Time Frame
From baseline to Week 12
Outcome Measure
Changes in Seated Trough Cuff Diastolic Blood Pressure (DBP) From Baseline to Week 12
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with UACR ≥30 mg/g at baseline, was evaluated.
Outcome Time Frame
From baseline to Week 12
Outcome Measure
Changes in Urinary Albumin: Creatinine Ratio (UACR) From Baseline to Week 12 for Participants With UACR ≥30 mg/g at Baseline
Outcome Description
Effect of KBP-5074 on UACR by assessing percentage changes in UACR for participants with UACR ≥30 mg/g at baseline, was evaluated. Here, overall number of participants analyzed field represents the number of participants assessed for this particular outcome measure at indicated time frame.
Outcome Time Frame
From baseline to Week 12 and Week 24
Outcome Measure
Percentage Changes in UACR From Baseline to Week 12 and Week 24 for Participants With UACR ≥30 mg/g at Baseline
Outcome Description
Effect of KBP-5074 on DBP by assessing change in seated trough cuff DBP was evaluated.
Outcome Time Frame
From baseline to Week 24
Outcome Measure
Changes in Seated Trough Cuff Diastolic Blood Pressure (DBP) From Baseline to Week 24
Outcome Description
Effect of KBP-5074 on DBP by assessing change in seated trough cuff SBP was evaluated.
Outcome Time Frame
From baseline to Week 48
Outcome Measure
Changes in Seated Trough Cuff DBP From Baseline to Week 48
Outcome Description
Effect of KBP-5074 on SBP by assessing change in seated trough cuff SBP was evaluated.
Outcome Time Frame
From baseline to Week 48
Outcome Measure
Changes in Seated Trough Cuff SBP From Baseline to Week 48
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with UACR ≥30 mg/g at baseline was evaluated.
Outcome Time Frame
From baseline to Week 24
Outcome Measure
Changes in UACR From Baseline to Week 24 for Participants With UACR ≥30 mg/g at Baseline
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with macroalbuminuria (defined as UACR ≥300 mg/g) at baseline was evaluated.
Outcome Time Frame
From baseline to Week 12, Week 24, and Week 48
Outcome Measure
Changes in UACR From Baseline to Week 12, Week 24, and Week 48 in Participants With Macroalbuminuria
Outcome Description
Effect of KBP-5074 on UACR by assessing percentage changes in UACR for participants with macroalbuminuria (defined as UACR ≥300 mg/g) at baseline was evaluated.
Outcome Time Frame
From baseline to Week 12, Week 24, and Week 48
Outcome Measure
Percentage Changes in UACR From Baseline to Week 12, Week 24, and Week 48 in Participants With Macroalbuminuria
Outcome Description
Effect of KBP-5074 on DBP by assessing change in seated trough cuff DBP was evaluated.
Outcome Time Frame
From Week 48 to Week 52
Outcome Measure
Change in Seated Trough Cuff DBP From Week 48 to Week 52
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with UACR ≥30 mg/g was evaluated. Here, overall number of participants analyzed field represents the number of participants assessed for this particular outcome measure at indicated time frame.
Outcome Time Frame
Week 48 to Week 52
Outcome Measure
Change in UACR From Week 48 to Week 52 for Participants With UACR ≥30 mg/g at Baseline
Outcome Description
Effect of KBP-5074 on UACR by assessing percentage changes in UACR for participants with UACR ≥30 mg/g was evaluated. Here, overall number of participants analyzed field represents the number of participants assessed for this particular outcome measure at indicated time frame.
Outcome Time Frame
From Week 48 to Week 52
Outcome Measure
Percentage Change in UACR From Week 48 to Week 52 in Participants With UACR ≥30 mg/g at Baseline
Outcome Description
The safety and tolerability of KBP-5074 was evaluated.
A treatment emergent adverse event (TEAE) was defined as any AE with onset during or after first dose and before 4 weeks after last dose of study drug, or any preexisting AE/condition that worsened during this period.
Selected TEAEs include Hyperkalemia, Hypertension, Hypotension, and eGFR Decrease.
A treatment emergent adverse event (TEAE) was defined as any AE with onset during or after first dose and before 4 weeks after last dose of study drug, or any preexisting AE/condition that worsened during this period.
Selected TEAEs include Hyperkalemia, Hypertension, Hypotension, and eGFR Decrease.
Outcome Time Frame
Until end of study (EOS) (Week 56) or Unscheduled visit or end of treatment or early termination (up to 32 months)
Outcome Measure
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with microalbuminuria (defined as UACR ≥30 and \<300 mg/g) at baseline, was evaluated.
Outcome Time Frame
From baseline to Week 12, Week 24, and Week 48
Outcome Measure
Changes in UACR From Baseline to Week 12, Week 24, and Week 48 in Participants With Microalbuminuria
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with microalbuminuria (defined as UACR ≥30 and \<300 mg/g) at baseline was evaluated.
Outcome Time Frame
From baseline to Week 12, Week 24, and Week 48
Outcome Measure
Percentage Changes in UACR From Baseline to Week 12, Week 24, and Week 48 in Participants With Microalbuminuria
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with microalbuminuria (defined as UACR ≥30 and \<300 mg/g) at baseline, was evaluated. Here, overall number of participants analyzed field represents the number of participants assessed for this particular outcome measure at indicated time frame.
Outcome Time Frame
From Week 48 to Week 52
Outcome Measure
Change in UACR From Week 48 to Week 52 in Participants With Microalbuminuria
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with microalbuminuria (defined as UACR ≥30 and \<300 mg/g) at baseline was evaluated. Here, overall number of participants analyzed field represents the number of participants assessed for this particular outcome measure at indicated time frame.
Outcome Time Frame
From Week 48 to Week 52
Outcome Measure
Percentage Change in UACR From Week 48 to Week 52 in Participants With Microalbuminuria
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with macroalbuminuria (defined as UACR ≥300 mg/g) at baseline was evaluated. Here, overall number of participants analyzed field represents the number of participants assessed for this particular outcome measure at indicated time frame.
Outcome Time Frame
From Week 48 to Week 52
Outcome Measure
Change in UACR From Week 48 to Week 52 in Participants With Macroalbuminuria
Outcome Description
Effect of KBP-5074 on UACR by assessing changes in UACR for participants with macroalbuminuria (defined as UACR ≥300 mg/g) at baseline was evaluated. Here, overall number of participants analyzed field represents the number of participants assessed for this particular outcome measure at indicated time frame.
Outcome Time Frame
From Week 48 to Week 52
Outcome Measure
Percentage Change in UACR From Week 48 to Week 52 in Participants With Macroalbuminuria
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Matthew Abramowitz
Investigator Email
matthew.abramowitz@einsteinmed.org
Categories Mesh Debug
Kidney & Urinary Tract --- RENAL INSUFFICIENCY, CHRONIC
Heart/Cardiovascular --- HYPERTENSION
Kidney & Urinary Tract --- KIDNEY DISEASES
Kidney & Urinary Tract --- UROLOGIC DISEASES
Heart/Cardiovascular --- VASCULAR DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
MeSH Terms
RENAL INSUFFICIENCY, CHRONIC
HYPERTENSION
RENAL INSUFFICIENCY
KIDNEY DISEASES
UROLOGIC DISEASES
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
MALE UROGENITAL DISEASES
CHRONIC DISEASE
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
VASCULAR DISEASES
CARDIOVASCULAR DISEASES
KBP-5074