Ferric Carboxymaltose (FCM) Assessment in Subjects With Iron Deficiency Anaemia and Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)

Chronic Kidney Disease Clinical Trial

— FIND-CKD  

Official title:

An Open-label, Multicentre, Randomised, 3-arm Study to Investigate the Comparative Efficacy and Safety of Intravenous Ferric Carboxymaltose (Ferinject High and Low Dosage Regimens) Versus Oral Iron for the Treatment of Iron Deficiency Anaemia in Subjects With Non-dialysis-dependent Chronic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00994318
• Other study ID #: FER-CKD-01
• Status: Completed
• Phase: Phase 3
• First received: October 12, 2009
• Last updated: May 9, 2014
• Start date: December 2009
• Est. completion date: February 2014

Study information

• Verified date: May 2014
• Source: Vifor Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationAustria: Agency for Health and Food SafetyBelgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlDenmark: Danish Health and Medicines AuthorityFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreece: Ministry of Health and WelfareItaly: The Italian Medicines AgencyNetherlands: Medicines Evaluation Board (MEB)Norway: Norwegian Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPortugal: National Pharmacy and Medicines InstituteRomania: National Medicines AgencySpain: Ministry of Health and ConsumptionSweden: Medical Products AgencySwitzerland: SwissmedicTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Phase IIIb study to evaluate the long-term efficacy of ferric carboxymaltose (FCM) (using targeted ferritin levels to determine dosing) or oral iron in non-dialysis-dependent chronic kidney disease (NDD-CKD) subjects with iron deficiency anaemia (IDA).

Description:

After an initial screening period of up to 4 weeks, eligible subjects were randomised (1:1:2) to 1 of the following 3 treatment arms for a period of 52 weeks.

1. FCM regimen (maximum single intravenous doses of 1,000 mg of iron) targeting a ferritin level of 400-600 mcg/L.

2. FCM regimen (maximum single intravenous doses of 200 mg of iron) targeting a ferritin level of 100-200 mcg/L.

3. Daily oral iron with 200 mg iron/day (100 mg twice daily)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 626
• Est. completion date: February 2014
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. At least 18 years of age.

2. NDD-CKD subjects with an estimated glomerular filtration rate (eGFR) =60 mL/min/1.73 m2 using modification of diet in renal disease 4 (MDRD-4) calculation.

3. NDD-CKD subjects with an eGFR loss =12 mL/min/1.73 m2/year and a predicted eGFR of =15 mL/min/1.73 m2 in 12 months.

4. Any single Hb between 9 and 11 g/dL within 4 weeks of randomisation. A value taken as part of routine medical care was used.

5. Any single serum ferritin <100 mcg/L or <200 mcg/L with TSAT <20% within 4 weeks of randomisation. Measurements taken as part of routine medical care were used.

6. ESA naïve; no exposure to ESA in last 4 months prior to randomisation.

7. Females of childbearing potential must have had a negative pregnancy test, using any medically acceptable assessment, prior to randomisation.

8. Before any study specific procedure, the appropriate written informed consent must have been obtained.

Exclusion Criteria:

1. History of acquired iron overload.

2. Known hypersensitivity reaction to any component of ferrous sulphate or FCM. Subjects with hypersensitivity to other forms of iron were permitted to participate.

3. Documented history of discontinuing oral iron products due to significant gastrointestinal (GI) distress.

4. Screening TSAT >40%.

5. Known active infection, C-reactive protein >20 mg/L, clinically significant overt bleeding, active malignancy (i.e., clinical evidence of current malignancy or not in stable remission for at least 5 years since completion of last treatment with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia).

6. History of chronic alcohol abuse (alcohol consumption >40 g/day).

7. Chronic liver disease and/or screening alanine transaminase or aspartate transaminase above 3 times the upper limit of the normal range.

8. Active human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome or active hepatitis B or C virus infection.

9. Anaemia due to reasons other than iron deficiency (e.g., haemoglobinopathy). Subjects with treated Vitamin B12 or folic acid deficiency were permitted.

10. IV iron and/or blood transfusion in previous 30 days prior to screening (or during the screening period).

11. Oral iron therapy at doses >100 mg/day dosing must have been discontinued at least 1 week prior to randomisation. If subject had received this therapy for >3 months (at doses >100 mg/day) then subject was not eligible. Ongoing use of multivitamins containing iron was permitted.

12. Immunosuppressive therapy that may have led to anaemia (e.g., cyclophosphamide, azathioprine, or mycophenolate mofetil). Steroid therapy was permitted.

13. Currently requiring renal dialysis.

14. Anticipated dialysis or transplant during the study.

15. Anticipated need for surgery that may have resulted in significant bleeding (>100 mL).

16. Currently suffering from chronic heart failure New York Heart Association Class IV.

17. Poorly controlled hypertension (>160 mmHg systolic pressure or >100 mmHg diastolic pressure).

18. Acute coronary syndrome or stroke within the 3 months prior to screening.

19. Currently suffering from concomitant, severe psychiatric disorders or other conditions which, in the opinion of the Investigator, would have made participation unacceptable.

20. Subject was not using adequate contraceptive precautions.

21. Subject of childbearing potential was evidently pregnant (e.g., positive human chorionic gonadotropin test) or was breast feeding.

22. Body weight <35 kg.

23. Subject currently was enrolled in or had not yet completed at least 30 days since ending other investigational device or drug studies, or subject was receiving other investigational agent(s).

24. Subject would not be available for follow-up assessment.

25. Subject had any kind of disorder that compromised the ability of the subject to give written informed consent and/or to comply with study procedures.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Chronic Kidney Disease
• Deficiency Diseases
• Iron Deficiency Anaemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• FCM (Ferric carboxymaltose) high ferritin target

• FCM (Ferric carboxymaltose) low ferritin target

• Oral Iron (Ferrous sulphate)

Locations

Country	Name	City	State
Australia	Gosford Hospital - Renal Research	Gosford
Austria	Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin IV	Innsbruck
Belgium	RHMS Baudour - Department of Nephrology and Dialysis	Baudour
Czech Republic	Nemocnice s poliklinikou v Novem Jicine, p.o. p.o. Interni oddeleni - nefrologie a dialyza	Novy Jicin
Denmark	Lillebalt Frederica Sygehus Department of Nephrology	Frederica
France	CHU grenoble - Service de Nephrologie	Grenoble Cedex
Germany	Praxis Dr. Kraatz	Demmin
Greece	General Hospital of Arta - Nephrology Department	Arta
Italy	Ospedali Riuniti Anzio-Nettuno ASL ROMA H U.O. Nefrologia e Dialisi	Anzio
Netherlands	Meander Medisch Centrum - Locatie Amersfoort Lichtenberg	Amersfoort
Norway	St. Olav's Hospital	Trondheim
Poland	Miedzyleski Szpital Spec. Oddzial I Wewnetrzny I Nefrologii	Warszawa
Portugal	Hospital Santa Maria - Nefrologia	Lisboa
Romania	Spitalul Clinic de Nefrologie"Dr Carol Davila"	Bucuresti
Spain	Hospital Universitario Marqués de Valdecilla - Servicio de Nefrología	Santander
Sweden	Karolinska University Hospital	Stockholm
Turkey	Cukurova University Medical Faculty Balcali Hospital - Department of Nephrology	Adana
United Kingdom	King's College Hospital	London
United States	Trial Management Associates	Wilmington	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Vifor Inc.	ICON Clinical Research, Luitpold Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Czech Republic,  Denmark,  France,  Germany,  Greece,  Italy,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kaplan-Meier Survival Analysis for Time to Other Anemia Therapy or Hb Trigger	Endpoint reported number of participants with/without events and was reached: First time of initiation of additional or alternative anaemia management,; First time the subject reached the Hb trigger.; 3 primary comparisons using a hierarchical step-down procedure on the log-rank test to preserve an alpha level of 0.05, performed in the following order: FCM (high ferritin target) compared with oral iron.; FCM (high ferritin target) compared with FCM (low ferritin target).; FCM (low ferritin target) compared with oral iron.; Sensitivity analyses of the primary endpoint were performed using the following alternative definitions of time to initiation of additional or alternative anaemia management: Without taking into account the Hb trigger.; Taking into account the Hb trigger based on local laboratory data, instead of central laboratory data.; Taking into account the Hb trigger based on subjects with a complete set of Hb values from the central laboratory.	Up to 1 year after baseline	No