Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301)
© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA..
BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD).
METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus.
RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation.
CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association - (2024) vom: 07. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhuang, Bing [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Clinical study |
|---|
| Anmerkungen: |
Date Revised 07.03.2024 published: Print-Electronic ClinicalTrials.gov: NCT04551300 Citation Status Publisher |
|---|
| doi: |
10.1093/ndt/gfae053 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369431782 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369431782 | ||
| 003 | DE-627 | ||
| 005 | 20240308233203.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240308s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/ndt/gfae053 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1320.xml |
| 035 | |a (DE-627)NLM369431782 | ||
| 035 | |a (NLM)38453435 | ||
| 035 | |a (PII)gfae053 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhuang, Bing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301) |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 07.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04551300 | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA. | ||
| 520 | |a BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD) | ||
| 520 | |a METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus | ||
| 520 | |a RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation | ||
| 520 | |a CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a VS-505 | |
| 650 | 4 | |a clinical study | |
| 650 | 4 | |a hemodialysis | |
| 650 | 4 | |a hyperphosphatemia | |
| 650 | 4 | |a phosphate binder | |
| 700 | 1 | |a Gan, Liangying |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Weijie |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Ai |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lihua |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaolan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Tongqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shiying |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Song |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Baoxing |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Huixiao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Changhua |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Hongli |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yiwen |e verfasserin |4 aut | |
| 700 | 1 | |a He, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Kanghui |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Junwei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yingxue Cathy |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhizheng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaolin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Weifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zuo, Li |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association |d 1990 |g (2024) vom: 07. März |w (DE-627)NLM012639206 |x 1460-2385 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:07 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/ndt/gfae053 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 07 |c 03 | ||