A Phase 2 Study to Evaluate the Safety and Efficacy of VS-505(AP301) to Treat Hyperphosphatemia in Hemodialysis Patients

Study Overview
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Brief Summary
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A multi-center, open-label, parallel-design, active-controlled phase 2 study to evaluate the tolerability, safety and efficacy of various dosages of VS-505 compared with Sevelamer Carbonate when given orally with meal for 6 weeks to treat hyperphosphatemia in chronic kidney disease subjects receiving maintenance hemodialysis.

Detailed Description
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The main body of this study has 5 intervention arms, 4 VS-505 treatment arms of various dosage plus 1 active control arm of Sevelamer Carbonate, each consists 25 subjects. Prior to this main part, a dose escalating cohort of 25 subjects is added to evaluate the tolerability of VS-505 in Chinese patient population.

Official Title
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A Phase 2 Study to Evaluate the Safety and Efficacy of Escalated and Fixed Doses of VS-505(AP301) in Comparison With Sevelamer Carbonate to Treat Hyperphosphatemia in Chronic Kidney Disease Patients Receiving Hemodialysis

Conditions
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Hyperphosphatemia

Intervention / Treatment
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* Drug: VS-505
* Drug: Sevelamer Carbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with end stage renal disease who are receiving a stable hemodialysis regimen (3 times per week) with sufficient dialysis adequacy; Serum phosphorus level range from >1.94 mmol/L (6.0 mg/dL) to ≤3.23 mmol/L (10.0 mg/dL) at the end of washout phase. Exclusion Criteria: Kidney transplant patient or scheduled kidney transplant, or change to peritoneal dialysis, home hemodialysis or plan to relocate to another dialysis center during the study period； Serum phosphorus level is <1.29 mmol/L（4.0 mg/dL) or >2.42 mmol/L（7.5 mg/dL) at screening, or documented to be >3.23 mmol/L（10 mg/dL) within the latest three month prior to screening (screening included); Serum calcium level is <8 mg/dL or >11 mg/dL at the screening; Serum immunoreactive parathyroid hormone (iPTH)>1000 pg/mL at the screening; History of hemochromatosis or serum ferritin value ≥1000 μg/L at screening； Current clinically significant gastrointestinal (GI) disorder, or history of intestine obstruction, gastrectomy or duodenectomy, or GI tract surgery within 12 weeks prior to screening; Poorly controlled hypertension, cardiovascular disorders, and history of cerebrovascular disease or cardiovascular disease event within 24 weeks (6 months) prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 4 different dosages of VS-505 in Comparison with Sevelamer Carbonate
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VS-505 500mg<br>VS-505 500mg (two 250 mg capsules) oral administration three times a day with meal, daily total dosage 1500mg. | Drug: VS-505<br>* 4 dosages of experimental drug<br>|
| Experimental: VS-505 750mg<br>VS-505 750mg (one 750 mg capsule) oral administration three times a day with meal, daily total dosage 2250mg. | Drug: VS-505<br>* 4 dosages of experimental drug<br>|
| Experimental: VS-505 1500mg<br>VS-505 1500mg (two 750 mg capsules) oral administration three times a day with meal, daily total dosage 4500mg. | Drug: VS-505<br>* 4 dosages of experimental drug<br>|
| Experimental: VS-505 2250mg<br>VS-505 2250mg (three 750 mg capsules) oral administration three times a day with meal, daily total dosage 6750mg. | Drug: VS-505<br>* 4 dosages of experimental drug<br>|
| Active Comparator: Sevelamer Carbonate 1600mg<br>Sevelamer Carbonate 1600mg (two 800mg pills) oral administration three times a day with meal, daily total dosage 4800mg. | Drug: Sevelamer Carbonate<br>* Active Comparator<br>* Other names: Renvela;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum phosphorus change from baseline to end of treatment |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to serum phosphorus response，defined as serum phosphorus level decrease by 0.32 mmol/L（1 mg/dL）and serum phosphorus level below 1.78 mmol/L（5.5 mg/dL） |  | 6 weeks | 
| The achievement rate of subjects with serum phosphorus in the target range 1.13-1.78 mmol/L（3.5-5.5 mg/dL）by the end of treatment |  | 6 weeks | 
| Serum calcium change from baseline to end of treatment |  | 6 weeks | 
| Serum Ca×P change from baseline to end of treatment |  | 6 weeks | 
| Serum iPTH change from baseline to end of treatment |  | 6 weeks |