FGF23 Reduction : Efficacy of a New Phosphate Binder in CHronic Kidney Disease

NCT01220843 | Completed Phase 3 DMC

• 2 other identifiers: PI10-PR-CHOUKROUN-12010-020872-49
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 15

Brief Summary

The purpose of this study is to evaluate in Chronic Kidney Disease (CKD) patients not on dialysis and who have an Fibroblast growth factor 23 (FGF23) serum levels elevated, the effect of non calcic phosphate binder: sevelamer carbonate. This treatment could lead to a diminution of FGF23 serum levels due to the diminution of intestinal absorption of dietary phosphate. In addition, the investigators will describe the impact of the FGF23 level monitoring on the main phosphocalcium metabolism markers as phosphatemia, intact parathyroid hormone (iPTH), serum calcitriol and phosphaturia.

Conditions

Chronic Renal Failure

Keywords

chronic renal failure; FGF23; Sevelamer carbonate

Outcome Measures

Primary Outcomes (1)

• Measurement of the serum levels of C terminal segment of fibroblast growth factor 23 (FGF23) and evaluation of sevelamer carbonate effect on this levels in comparison with placebo

  Indeed the sevelamer carbonate could lead to a diminution of FGF23 serum levels due to the diminution of intestinal absorption of dietary phosphate.

  12 weeks after the beginning of treatment

Secondary Outcomes (8)

• Evaluation of sevelamer carbonate effect on the serum levels of iPTH

  12 weeks after the beginning of treatment

• Evaluation of sevelamer carbonate effect on the serum levels of calcitriol (1 25(OH)2D3)

  12 weeks after the beginning of treatment

• Evaluation of sevelamer carbonate effect on the serum levels of others mineral metabolism parameters (phosphore, calcium, intact FGF-23 , 25(OH)D3, bone specific alkaline phosphatases, osteocalcin, collagen crosslink, C reactive protein)

  12 weeks after the beginning of treatment

• Evaluation of sevelamer carbonate effect on the urinary levels of phosphate

  12 weeks after the beginning of treatment

• Evaluation of sevelamer carbonate effect on the urinary levels of calcium

  12 weeks after the beginning of treatment

Study Arms (2)

Placebo

PLACEBO COMPARATOR

DOuble blinded, same labels than the active drug same dosage (2 tablets 3 times per day) during the meal

Drug: Placebo

Sevelamer carbonate

EXPERIMENTAL

DOuble blinded, dosage 2 tablets 3 times per day corresponding to 4.8/d to taken during meals

Drug: Sevelamer carbonate

Interventions

Placebo DRUG

dosage : 2 tablets 3 times per day corresponding taken during meals during 12 weeks

Placebo

Sevelamer carbonate DRUG

dosage : 2 tablets 3 times per day corresponding taken during meals during 12 weeks ( each tablet :800mg sevelamer carbonate

Also known as: Renvela 800

Sevelamer carbonate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who gave their written consent
• Women or men over 18 years
• No concomitant treatment with phosphate binders
• CKD patients not on dialysis stage 3b or 4, as a GFR (glomerular filtration rate) between 15 and 45 ml/min/1.73m2, using simplified MDRD formula
• Able to comply with the study procedures during all the study period
• Willing to abstain from taking any following medication during all the study period :antiacid and phosphate binders with aluminium, magnesium, calcium or lanthanum;Treatment for hyperparathyroid : active vitamin D and calcimimetic ; native vitamin D
• Female subjects who are of childbearing potential must have a reliable contraceptive methods during all the study period (hormonal, barrier methods or intrauterine device)
• No Participation in any clinical trial using an investigational product or device during the 30 days preceding the first protocol visit
• Informed patient who agreed with the utilisation of his data for the study
• Able to read and understand french and study objectives
• Inscription to medical assurance

You may not qualify if:

• predisposition with or presence of intestinal or ileus obstruction or severe gastrointestinal motility disorder(like severe constipation)
• Antecedent of major gastrointestinal surgery
• Abusive consumption of alcohol and drug (exclude tabacco) according the investigator
• Arrythmia treated by antiarrythmic agent or epilepsia treated by anticonvulsant
• Antecedent of kidney transplantation
• Antecedent of parathyroidectomy
• Pregnancy or breastfeeding

Sponsors & Collaborators

• Centre Hospitalier Universitaire, Amiens: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (15)

CHU Amiens service de nephrologie

Amiens, 8000, France

Location

CHU de Bordeaux Service de néphrologie

Bordeaux, 33076, France

Location

CHU Caen service de néphrologie

Caen, 14033, France

Location

CHU Lyon service de néphrologie

Lyon, 69437, France

Location

CHU Marseille Service de néphrologie

Marseille, 13385, France

Location

CHU de Montpellier Hôpital Lapeyronie Service de Néphrologie

Montpellier, 34295, France

Location

CHU de Nice Service de néphrologie

Nice, 06002, France

Location

Hôpital Tenon Service de Nephrologie

Paris, 75020, France

Location

Hôpital Européen Georges Pompidou Service de Nephrologie

Paris, 75098, France

Location

CHU Reims service de néphrologie

Reims, 51092, France

Location

CHU St Etienne Hopital Nord Service de néphrologie

Saint-Etienne, 42055, France

Location

Clinique du Landy Centre de dialyse

Saint-Ouen, 93400, France

Location

Néphrologie - Dialyse Centre de Rein Artificiel

Tassin-la-Demi-Lune, 69160, France

Location

CH Valenciennes hémodialyse

Valenciennes, 59322, France

Location

CHU de Nancy service de néphrologie

Vandeuvre Les Nancy, 54511, France

Location

Related Publications (23)

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  PMID: 17517792 BACKGROUND

• Levin A, Djurdjev O, Beaulieu M, Er L. Variability and risk factors for kidney disease progression and death following attainment of stage 4 CKD in a referred cohort. Am J Kidney Dis. 2008 Oct;52(4):661-71. doi: 10.1053/j.ajkd.2008.06.023.

  PMID: 18805347 BACKGROUND

• Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2005 Feb;16(2):520-8. doi: 10.1681/ASN.2004070602. Epub 2004 Dec 22.

  PMID: 15615819 BACKGROUND

• Vassalotti JA, Uribarri J, Chen SC, Li S, Wang C, Collins AJ, Calvo MS, Whaley-Connell AT, McCullough PA, Norris KC; Kidney Early Evaluation Program Investigators. Trends in mineral metabolism: Kidney Early Evaluation Program (KEEP) and the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Am J Kidney Dis. 2008 Apr;51(4 Suppl 2):S56-68. doi: 10.1053/j.ajkd.2007.12.018.

  PMID: 18359409 BACKGROUND

• Danziger J. The bone-renal axis in early chronic kidney disease: an emerging paradigm. Nephrol Dial Transplant. 2008 Sep;23(9):2733-7. doi: 10.1093/ndt/gfn260. Epub 2008 May 9. No abstract available.

  PMID: 18469306 BACKGROUND

• Inaba M, Okuno S, Imanishi Y, Yamada S, Shioi A, Yamakawa T, Ishimura E, Nishizawa Y. Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients. Osteoporos Int. 2006 Oct;17(10):1506-13. doi: 10.1007/s00198-006-0154-6. Epub 2006 Aug 5.

  PMID: 16896512 BACKGROUND

• Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, Ritz E, Kronenberg F; MMKD Study Group; Kuen E, Konig P, Kraatz G, Mann JF, Muller GA, Kohler H, Riegler P. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol. 2007 Sep;18(9):2600-8. doi: 10.1681/ASN.2006080936. Epub 2007 Jul 26.

  PMID: 17656479 BACKGROUND

• Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008 Aug 7;359(6):584-92. doi: 10.1056/NEJMoa0706130.

  PMID: 18687639 BACKGROUND

• Jean G, Terrat JC, Vanel T, Hurot JM, Lorriaux C, Mayor B, Chazot C. High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant. 2009 Sep;24(9):2792-6. doi: 10.1093/ndt/gfp191. Epub 2009 Apr 25.

  PMID: 19395730 BACKGROUND

• Peiskerova M, Kalousova M, Kratochvilova M, Dusilova-Sulkova S, Uhrova J, Bandur S, Malbohan IM, Zima T, Tesar V. Fibroblast growth factor 23 and matrix-metalloproteinases in patients with chronic kidney disease: are they associated with cardiovascular disease? Kidney Blood Press Res. 2009;32(4):276-83. doi: 10.1159/000243050. Epub 2009 Oct 1.

  PMID: 19797911 BACKGROUND

• JP Cristol, AS Bargnoux, AM Dupuy, M Morena, A Avignon and B Canaud. Biological markers of vascular calcifications in uremia. Médecine Nucléaire 2009; 33, 53-61.

  BACKGROUND

• Stubbs JR, Quarles LD. Fibroblast growth factor 23: uremic toxin or innocent bystander in chronic kidney disease? Nephrol News Issues. 2009 May;23(6):33-4, 36-7.

  PMID: 19534362 BACKGROUND

• Westerberg PA, Linde T, Wikstrom B, Ljunggren O, Stridsberg M, Larsson TE. Regulation of fibroblast growth factor-23 in chronic kidney disease. Nephrol Dial Transplant. 2007 Nov;22(11):3202-7. doi: 10.1093/ndt/gfm347. Epub 2007 Jun 13.

  PMID: 17567652 BACKGROUND

• Shigematsu T, Kazama JJ, Yamashita T, Fukumoto S, Hosoya T, Gejyo F, Fukagawa M. Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis. 2004 Aug;44(2):250-6. doi: 10.1053/j.ajkd.2004.04.029.

  PMID: 15264182 BACKGROUND

• Tanaka H, Hamano T, Fujii N, Tomida K, Matsui I, Mikami S, Nagasawa Y, Ito T, Moriyama T, Horio M, Imai E, Isaka Y, Rakugi H. The impact of diabetes mellitus on vitamin D metabolism in predialysis patients. Bone. 2009 Nov;45(5):949-55. doi: 10.1016/j.bone.2009.07.016. Epub 2009 Jul 23.

  PMID: 19631779 BACKGROUND

• Urena Torres P, Friedlander G, de Vernejoul MC, Silve C, Prie D. Bone mass does not correlate with the serum fibroblast growth factor 23 in hemodialysis patients. Kidney Int. 2008 Jan;73(1):102-7. doi: 10.1038/sj.ki.5002622. Epub 2007 Oct 17.

  PMID: 17943081 BACKGROUND

• Nagano N, Miyata S, Abe M, Kobayashi N, Wakita S, Yamashita T, Wada M. Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats. Kidney Int. 2006 Feb;69(3):531-7. doi: 10.1038/sj.ki.5000020.

  PMID: 16395276 BACKGROUND

• Oliveira RB, Cancela AL, Graciolli FG, Dos Reis LM, Draibe SA, Cuppari L, Carvalho AB, Jorgetti V, Canziani ME, Moyses RM. Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol. 2010 Feb;5(2):286-91. doi: 10.2215/CJN.05420709. Epub 2009 Nov 12.

  PMID: 19965540 BACKGROUND

• Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009 Aug;(113):S1-130. doi: 10.1038/ki.2009.188.

  PMID: 19644521 BACKGROUND

• National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266. No abstract available.

  PMID: 11904577 BACKGROUND

• Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F; Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006 Aug 15;145(4):247-54. doi: 10.7326/0003-4819-145-4-200608150-00004.

  PMID: 16908915 BACKGROUND

• Liabeuf S, Ryckelynck JP, El Esper N, Urena P, Combe C, Dussol B, Fouque D, Vanhille P, Frimat L, Thervet E, Mentaverri R, Prie D, Choukroun G; FRENCH Study collaborators. Randomized Clinical Trial of Sevelamer Carbonate on Serum Klotho and Fibroblast Growth Factor 23 in CKD. Clin J Am Soc Nephrol. 2017 Dec 7;12(12):1930-1940. doi: 10.2215/CJN.03030317. Epub 2017 Oct 26.

  PMID: 29074818 RESULT

• Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.

  PMID: 40576086 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Sevelamer

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; 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

Intervention Hierarchy (Ancestors)

Polyamines; Amines; Organic Chemicals

Study Officials

• Gabriel Choukroun, Ph D, M D

  Centre Hospitalier Universitaire, Amiens

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2010
• First Posted: October 14, 2010
• Study Start: October 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: September 19, 2025

Record last verified: 2025-09

Locations

FR (15)