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AP301 Efficacy and Safety in Chinese Dialysis Patients With Hyperphosphatemia

Phase 3
Completed
Conditions
ESRD (End Stage Renal Disease)
Chronic Kidney Disease(CKD)
Hyperphosphatemia
Hyperphosphatemia in Chronic Kidney Disease
Dialysis
Chronic Kidney Disease, Receiving Dialysis
Interventions
Registration Number
NCT07030595
Lead Sponsor
Alebund Pharmaceuticals
Brief Summary

This Phase 3 clinical trial is the pivotal study of AP301 aiming to evaluate the efficacy and safety of AP301 for controlling serum phosphorus in chronic kidney disease receiving hemodialysis and peritoneal dialysis in Chinese patients with hyperphosphatemia.

Detailed Description

This study has two primary efficacy objectives. The primary efficacy objective 1 is to evaluate the superiority of maintenance dose versus low dose of AP301 on serum P control in dialysis patients with hyperphosphatemia. The primary efficacy objective 2 is to evaluate the non-inferiority of AP301 versus sevelamer carbonate on serum phosphorus control. Besides these two primary efficacy objectives, this study will also evaluate the serum phosphorus control equivalence and the safety for AP301 produced from two APIs (Active Pharmaceutical Ingredient) in the last 8 weeks of drug exposure.

Patients will start dosed after eligibility confirmation. The treatment period will last 52 weeks in total, including:

A) A 24-week sevelamer carbonate active control phase in which serum phosphorus level at the end of Week 12 will be measured for the analysis of primary efficacy endpoint 2, B) A 3-week AP301 low dose control phase in which serum phosphorus level at the end of Week 27 will be measured for the analysis of primary efficacy endpoint 1, and C) A 25 or 28-week extension treatment phase

The investigational treatments will be AP301. Sevelamer carbonate will be provided as active control in active control and extension treatment phase and AP301 125 mg as ineffective control in low dose control phase.

A) The starting dose of AP301 is one 700 mg capsule 3 times daily. The dosage is to be adjusted based on their serum phosphorus level and safety assessmentsevery two or four weeks. The maximal dose is to be 10 capsules daily.

B) The starting dose of sevelamer carbonate will be one to two 800 mg capsules 3 times daily. The dosage is to be adjusted based on their serum phosphorus level every and safety assessments two or four weeks. The maximal dose is to be 12 capsules daily.

Then, a 2-week safety observation will be followed after the last dosing.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
474
Inclusion Criteria
  • Provision of signed and dated ICF

  • Adult when signing the ICF

  • Patients on dialysis for ≥ 3 months before signing the ICF and throughout the study

  • For HD patients, spKt/V ≥ 1.2; for PD patients, total Kt/V ≥ 1.7/week

  • For patients who receive phosphate binders and their serum phosphate level is:

    1. Screening: 1.13 mmol/L (3.5 mg/dL) ≤ serum phosphate < 2.58 mmol/L (8.0 mg/dL)
    2. After washout: 1.94 mmol/L (6.0 mg/dL) ≤ serum phosphate < 3.23 mmol/L (10.0 mg/dL)
  • For patients who do not receive phosphate binders over 2 weeks and their serum phosphate level is:

    1. Screening: 1.94 mmol/L (6.0 mg/dL) ≤ serum phosphate < 3.23 mmol/L (10.0 mg/dL)

Key

Exclusion Criteria
  • History or plan of kidney transplantation
  • History or plan of parathyroid intervention 6 months before signing the ICF
  • Serum calcium < 1.9 mmol/L (7.6 mg/dL) or > 2.75 mmol/L (11 mg/dL) at screening
  • Serum intact parathyroid hormone > 110 pmol/L (1000 pg/mL) at screening
  • Presence of clinically significant gastrointestinal (GI) disorder
  • History of gastrectomy or duodenectomy, or GI surgery within 3 months before signing the ICF
  • Known allergic to any ingredient of AP301 or Sevelamer Carbonate, or known history of severe allergies leading to emergency medical care
  • Female who are breastfeeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AP301AP301A blood phosphate-lowering medication containing iron
Sevelamer CarbonateSevelamer carbonate (Renvela®)A marketed blood phosphate-lowering medication
AP301 Low DoseAP301 Low DoseA blood phosphate-lowering medication containing iron, but with a low dose considered as ineffective
Primary Outcome Measures
NameTimeMethod
Change in serum phosphorus levels between AP301 and AP301 low dose groups in hyperphosphatemic patientsFrom the end of Week 24 to the end of Week 27

The serum phosphorus will be measured with a standard laboratory test. The change in serum phosphorus levels will be compared between the group receiving AP301 and the group receiving AP301 low dose.

Change in serum phosphorus levels between AP301 and sevelamer carbonate groups in hyperphosphatemic patientsFrom Baseline to the end of Week 12

The serum phosphorus will be measured with a standard laboratory test. The change in serum phosphorus levels will be compared between the group receiving AP301 and the group receiving sevelamer carbonate.

Secondary Outcome Measures
NameTimeMethod
Changes in serum calcium times phosphorus productFrom Baseline to the end of Week 52

The serum calcium and phosphorus in the blood will be measured with standard laboratory tests.

The achievement rate of serum phosphorus in the target range 1.13-1.78 mmol/L (3.5-5.5 mg/dL) (both inclusive).From Baseline to the end of Week 52.

The serum phosphorus will be measured with a standard laboratory test.

Changes in serum calciumFrom Baseline to the end of Week 52

The serum calcium in the blood will be measured with a standard laboratory test.

Changes in intact parathyroid hormoneFrom Baseline to the end of Week 52

The intact parathyroid hormone in the blood will be measured with a standard laboratory test.

Changes in serum bone-specific alkaline phosphataseFrom Baseline to the end of Week 52

The serum bone-specific alkaline phosphatase in the blood will be measured with standard laboratory tests.

Changes in osteocalcinFrom Baseline to the end of Week 52

The serum osteocalcin in the blood will be measured with a standard laboratory test.

Number of adverse eventsFrom Baseline to Follow-up (up to 54 weeks)
Changes in serum iron parametersFrom Baseline to the end of Week 52

The serum iron parameters will be measured with standard laboratory tests.

Change in QT intervals measured by 12-lead electrocardiogram test over timeFrom Baseline to the end of Week 52

The duration of QT intervals will be measured with a standard 12-lead electrocardiogram test.

Number of participants with abnormal vital signsFrom Baseline to the end of Week 52

The vital sign will consist of pulse rate and blood pressure with standard measurements.

Number of participants with abnormal laboratory tests resultsFrom Baseline to the end of Week 52

The laboratory tests will be measured with standard validated methods, involving hematology, biochemistry, bone markers, iron parameters and others.

Trial Locations

Locations (50)

Beijing Anzhen Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

Peking University First Hospital

🇨🇳

Beijing, Beijing, China

Beijing Jishuitan Hospital

🇨🇳

Beijing, Beijing, China

Peking University People's Hospital

🇨🇳

Beijing, Beijing, China

Peking University Third Hospital

🇨🇳

Beijing, Beijing, China

Peking University International Hospital

🇨🇳

Beijing, Beijing, China

Beijing Tsinghua Changgung Hospital

🇨🇳

Beijing, Beijing, China

Jilin Province People's Hospital

🇨🇳

Jilin, Changchun, China

The Second Norman Bethune Hospital of Jilin University

🇨🇳

Jilin, Changchun, China

The First Affiliated Hospital of Xiamen University

🇨🇳

Xiamen, Fujian, China

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Beijing Anzhen Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
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