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

NCT00994318 | Completed Phase 3 Results DMC

• 1 other identifier: FER-CKD-01
• Study Type: interventional
• Target: 626
• Locations: 18 countries
• Sites: 18

Brief 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).

Conditions

Iron Deficiency Anaemia; Chronic Kidney Disease

Keywords

Ferinject Iron Deficiency Anaemia Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• 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: 1. FCM (high ferritin target) compared with oral iron. 2. FCM (high ferritin target) compared with FCM (low ferritin target). 3. 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: 1. Without taking into account the Hb trigger. 2. Taking into account the Hb trigger based on local laboratory data, instead of central laboratory data. 3. 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

Study Arms (3)

FCM (high ferritin target)

EXPERIMENTAL

Ferric carboxymaltose (FCM) (Ferinject / Injectafer) targeting ferritin level of 400 - 600 mcg/L

Drug: FCM (Ferric carboxymaltose) high ferritin target

FCM (low ferritin target)

EXPERIMENTAL

Ferric carboxymaltose (FCM) (Ferinject / Injectafer) targeting ferritin level of 100 - 200 mcg/L

Drug: FCM (Ferric carboxymaltose) low ferritin target

Oral Iron

ACTIVE COMPARATOR

Ferrous sulphate 100 mg iron twice daily, continuous

Drug: Oral Iron (Ferrous sulphate)

Interventions

FCM (Ferric carboxymaltose) high ferritin target DRUG

Also known as: Ferinject, Injectafer

FCM (high ferritin target)

FCM (Ferric carboxymaltose) low ferritin target DRUG

Also known as: Ferinject, Injectafer

FCM (low ferritin target)

Oral Iron (Ferrous sulphate) DRUG

Also known as: Ferrous sulphate

Oral Iron

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age.
• 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.
• 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.
• 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.
• 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.
• ESA naïve; no exposure to ESA in last 4 months prior to randomisation.
• Females of childbearing potential must have had a negative pregnancy test, using any medically acceptable assessment, prior to randomisation.
• Before any study specific procedure, the appropriate written informed consent must have been obtained.

You may not qualify if:

• History of acquired iron overload.
• Known hypersensitivity reaction to any component of ferrous sulphate or FCM. Subjects with hypersensitivity to other forms of iron were permitted to participate.
• Documented history of discontinuing oral iron products due to significant gastrointestinal (GI) distress.
• Screening TSAT \>40%.
• 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).
• History of chronic alcohol abuse (alcohol consumption \>40 g/day).
• Chronic liver disease and/or screening alanine transaminase or aspartate transaminase above 3 times the upper limit of the normal range.
• Active human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome or active hepatitis B or C virus infection.
• Anaemia due to reasons other than iron deficiency (e.g., haemoglobinopathy). Subjects with treated Vitamin B12 or folic acid deficiency were permitted.
• IV iron and/or blood transfusion in previous 30 days prior to screening (or during the screening period).
• 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.
• Immunosuppressive therapy that may have led to anaemia (e.g., cyclophosphamide, azathioprine, or mycophenolate mofetil). Steroid therapy was permitted.
• Currently requiring renal dialysis.
• Anticipated dialysis or transplant during the study.
• Anticipated need for surgery that may have resulted in significant bleeding (\>100 mL).

Sponsors & Collaborators

• Vifor Pharma: lead
• American Regent, Inc.: collaborator
• ICON Clinical Research: collaborator

Study Sites (19)

Trial Management Associates

Wilmington, North Carolina, 28401, United States

Location

Gosford Hospital - Renal Research

Gosford, 2250, Australia

Location

Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin IV

Innsbruck, 6020, Austria

Location

RHMS Baudour - Department of Nephrology and Dialysis

Baudour, 7331, Belgium

Location

Nemocnice s poliklinikou v Novem Jicine, p.o. p.o. Interni oddeleni - nefrologie a dialyza

Nový Jičín, 74101, Czechia

Location

Lillebalt Frederica Sygehus Department of Nephrology

Frederica, 7000, Denmark

Location

CHU grenoble - Service de Nephrologie

Grenoble, 38043, France

Location

Praxis Dr. Kraatz

Demmin, 17109, Germany

Location

General Hospital of Arta - Nephrology Department

Arta, 47100, Greece

Location

Ospedali Riuniti Anzio-Nettuno ASL ROMA H U.O. Nefrologia e Dialisi

Anzio, 00042, Italy

Location

Meander Medisch Centrum - Locatie Amersfoort Lichtenberg

Amersfoort, 3816 CP, Netherlands

Location

St. Olav's Hospital

Trondheim, 7006, Norway

Location

Miedzyleski Szpital Spec. Oddzial I Wewnetrzny I Nefrologii

Warsaw, 04-749, Poland

Location

Hospital Santa Maria - Nefrologia

Lisbon, 1649-035, Portugal

Location

Spitalul Clinic de Nefrologie"Dr Carol Davila"

Bucharest, 010731, Romania

Location

Hospital Universitario Marqués de Valdecilla - Servicio de Nefrología

Santander, 39008, Spain

Location

Karolinska University Hospital

Stockholm, 141, Sweden

Location

Cukurova University Medical Faculty Balcali Hospital - Department of Nephrology

Adana, 01330, Turkey (Türkiye)

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (3)

• Roger SD, Gaillard CA, Bock AH, Carrera F, Eckardt KU, Van Wyck DB, Cronin M, Meier Y, Larroque S, Macdougall IC; FIND-CKD Study Investigators. Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial. Nephrol Dial Transplant. 2017 Sep 1;32(9):1530-1539. doi: 10.1093/ndt/gfw264.

  PMID: 28339831 DERIVED

• Macdougall IC, Bock AH, Carrera F, Eckardt KU, Gaillard C, Van Wyck D, Meier Y, Larroque S, Roger SD; FIND-CKD Study investigators. Renal function in patients with non-dialysis chronic kidney disease receiving intravenous ferric carboxymaltose: an analysis of the randomized FIND-CKD trial. BMC Nephrol. 2017 Jan 17;18(1):24. doi: 10.1186/s12882-017-0444-6.

  PMID: 28095881 DERIVED

• Macdougall IC, Bock AH, Carrera F, Eckardt KU, Gaillard C, Van Wyck D, Roubert B, Nolen JG, Roger SD; FIND-CKD Study Investigators. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant. 2014 Nov;29(11):2075-84. doi: 10.1093/ndt/gfu201. Epub 2014 Jun 2.

  PMID: 24891437 DERIVED

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Renal Insufficiency, Chronic

Interventions

Fosfomycin; ferric carboxymaltose; Iron; ferrous sulfate

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; 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)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Limitations and Caveats

Initially 1,016 subjects were planned, but due to slow enrollment only 626 were randomised which was sufficient to make the primary comparison between FCM targeting high ferritin level and oral iron.

Results Point of Contact

• Title: Medical Information
• Organization: Vifor Pharma

medinfo@viforpharma.com

41 58 851 8222

Study Officials

• Iain Macdougall

  King's College Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2009
• First Posted: October 14, 2009
• Study Start: December 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2014
• Last Updated: May 20, 2014
• Results First Posted: May 7, 2014

Record last verified: 2014-05

Locations

US (1); AU (1); ES (1); FR (1); PL (1); RO (1); GR (1); IT (1); BE (1); PT (1); TU (1); CZ (1); GB (1); DE (1); DK (1); NL (1); NO (1); SE (1)