To Assess the Impact of Ferric Carboxymaltose Compared With Iron Sucrose in Chinese Subjects on Correcting Iron Deficiency Anaemia

Study Overview
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Brief Summary
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The primary objective is to demonstrate the efficacy of ferric carboxymaltose (FCM) given in a simple dosing regimen in correcting iron deficiency anaemia (IDA), by demonstrating non-inferiority to treatment with the currently approved intravenous (IV) iron therapy of iron sucrose (IS, Venofer™) in the Chinese population. The secondary objectives are to assess the safety of FCM compared to IS in the Chinese population and to evaluate the effect of FCM compared to IS on relevant laboratory parameters (haematology, chemistry, iron parameters) in the Chinese population.

Detailed Description
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This is an open-label, randomised controlled study to assess the impact of FCM in correcting iron deficiency anaemia compared with Venofer™ (IS). All subjects, after providing written informed consent and meeting the eligibility assessments, will receive a first dose of IV iron as either FCM or IS. A total of approximately 368 subjects (184 per group) will be enrolled. All subjects will have iron deficiency anaemia as measured by haemoglobin (Hb), serum ferritin and transferrin saturation (TSAT) at screening. Ferric carboxymaltose will be administered as either a diluted infusion or undiluted injection (at Investigator discretion) and IS will be administered as a slow intravenous injection at a rate of 1 ml undiluted solution per minute (with each single injection of 200 mg iron) or by drip infusion. Note, for subjects randomised to receive IS dosing visits are required three times a week to achieve total iron repletion dosing as calculated using the Ganzoni formula. For subjects randomised to FCM, the total iron requirements will be calculated at screening based on the screening Hb and subject weight. Dosing will be at baseline and, if required, at day 8 and day 15. All subjects will attend study visits at screening, baseline and thereafter at Weeks 2, 4 and 6. All subjects will attend an end of study visit (at Week 8 - or earlier if discontinued prematurely).

Official Title
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An Open-label, Randomised Controlled Multi-centre Study to Assess the Impact of Ferric Carboxymaltose in Correcting Iron Deficiency Anaemia Compared With Venofer® (Iron Sucrose) in Chinese Subjects

Conditions
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Iron Deficiency Anemia

Intervention / Treatment
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* Drug: Ferric carboxymaltose
* Drug: Iron sucrose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age Hb <11 g/dL (females) or Hb <12 g/dL (males) at the screening visit Serum ferritin <100 ng/mL for subjects with underlying inflammatory disease (e.g., inflammatory bowel disease (IBD), chronic kidney disease (CKD) or chronic heart failure (CHF), as determined by high sensitive C-reactive protein [hsCRP] levels above the normal range) otherwise ≤14 ng/mL in subjects with no apparent underlying inflammatory disease (as determined by hsCRP levels within normal range) at the screening visit Transferrin Saturation (TSAT) <16% (any subject) at the screening visit Microcytic, hypochromic anaemia defined as: a) Mean corpuscular Hb concentration (MCHC) <32%; b) Mean corpuscular volume (MCV) < 80 fL; c)Mean corpuscular Hb (MCH) <27 pg Subjects with the ability to understand the requirements of the study and abide by the study restrictions, and who agree to return for the required assessments Before any study-specific procedure is conducted, the appropriate written informed consent must be obtained Exclusion Criteria: Subject has known hypersensitivity to any of the products to be administered during dosing Any history of iron storage diseases such as haemochromatosis Any history or clinical findings of iron utilisation disorders such as sideroachrestic anaemia Known haemoglobinopathy (e.g. thalassaemia) Any history or clinical findings of anaemia associated with: a) Haematuria b) Vitamin B12 or folic acid deficiency that requires treatment (subjects can be included after deficiency is corrected) Any allergic predispositions, i.e. any history of asthma or atopic allergy. This includes drug allergies. Planned surgery with anticipated blood loss (defined as Hb drop >2 g/dL) in the 3 months post randomisation Subject has known malignancy (with or without current treatment), except basal cell or squamous cell carcinoma of the skin or cervical intra-epithelial neoplasia Haemodialysis (current or planned within the next 3 months) History of IV iron therapy, erythropoiesis stimulating agent (ESA) therapy and/or blood transfusion in previous 4 weeks prior to screening, and oral iron or oral iron-containing products including Chinese herbal medicines (>75mg iron/day) in the 7 days prior to screening Body weight <35 kg Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST) above 3 times the upper limit of the normal range Known human immunodeficiency virus infection, acquired immunodeficiency syndrome, tuberculosis Known active hepatitis B or C or other active infection (acute or chronic) Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(ies), or subject is receiving other investigational agent(s) Subject is pregnant or is breast feeding Female subject of childbearing potential not using adequate contraceptive methods during the study and for up to 1 month after the last dose of the study medication. Adequate contraceptive methods are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomised partner. Non-childbearing potential includes being surgically sterilised at least 6 months prior to the study or post-menopausal, defined as amenorrhoea for at least 12 months Male subjects planning to father a child within 7 days from the last study drug administration. Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures and/or other reason(s) that render subject not appropriate for study participation in the opinion of the treating physician

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: Open-label, parallel design, randomised controlled multi-centre trial in Chinese subjects
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferric carboxymaltose (FCM)<br>Subjects treated with FCM given by IV injection or drip infusion | Drug: Ferric carboxymaltose<br>* Dosage Form: Injection, Sterile FCM solution as a 5% w/v iron solution in water for injection Strength: 10 mL vials containing 500 mg iron per vial Dosage: 500mg/week or 1000mg/week (based on subject BW and Hb value at screening) Route of administration: IV injection (undiluted solution) or drip infusion (500 mg iron diluted in 100 mL 0.9% w/v physiological saline or 1,000 mg iron diluted in 250 mL 0.9% w/v physiological saline) Dosing schedules: baseline (Day 1) and, if required, at Day 8 and Day 15.<br>* Other names: FCM;|
| Active Comparator: Iron sucrose (IS)<br>Subjects treated with IS given by IV injection or drip infusion | Drug: Iron sucrose<br>* Dosage Form: Sterile solution for injection containing 2% w/v iron Strength: 5 mL ampoules containing 100 mg iron per ampoule Dosage: single doses of IS of 200mg iron based on the formula of Ganzoni: Cumulative iron deficit [mg] = BW [kg] x (target Hb- actual Hb) [g/dL] x 2.4 + 500 mg, up to 11 IS injections will be given Route of administration: IV injection or drip infusion Dosing schedules: three times a week, with an initial dose at baseline and will receive iron, as per approved label, until the subject has received the calculated iron dose.<br>* Other names: Venofer™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants Achieving an Increase in Hb of at Least 2 g/dL at Any Time up to Week 8 | Haemoglobin (Hb) | From baseline at any time up to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants Achieving an Increase in Hb of at Least 2 g/dL From Baseline to Weeks 2, 4, 6 and 8 | Haemoglobin (Hb) | From Baseline to weeks 2, 4, 6 and 8 | 
| Change in Hb From Baseline to Weeks 2, 4, 6, and 8 | Haemoglobin (Hb) | From Baseline to weeks 2, 4, 6 and 8 | 
| Participants With Iron Deficiency Correction Over Time by Treatment | Iron deficiency correction: TSAT >= 16% and serum ferritin >=100ng/mL (for subjects with underlying inflammatory disease) or >14ng/mL (for subjects with no apparent underlying inflammatory disease). | From Baseline to Weeks 2, 4, 6 and 8 | 
| Change in TSAT From Baseline to Weeks 2, 4, 6 and 8 | Transferrin saturation (TSAT) | From Baseline to weeks 2, 4, 6 and 8 | 
| Change in Serum Ferritin From Baseline to Weeks 2, 4, 6 and 8 |  | From Baseline to Weeks 2, 4, 6 and 8 | 
| Change in Serum Iron From Baseline to Weeks 2, 4, 6 and 8 |  | From Baseline to weeks 2, 4, 6 and 8 | 
| Participants With Any Treatment Emergent Adverse Event (TEAE) | Please note that in this section we are presenting just the overview of the adverse events experienced by the trial participant, in particular, the number of participants with at least one TEAE until end of the trial. Please refer to the detailed tables included on the Adverse Event Module for specifics | From Baseline to the End of the study (week 8) | 
| Blood Pressure at Baseline and Weeks 2, 4, 6 and 8 | Diastolic Blood pressure | Baseline and weeks 2, 4, 6 and 8 | 
| Body Weight at Baseline and Week 8 |  | Baseline and week 8 | 
| Heart Rate at Baseline and Weeks 2, 4, 6 and 8 |  | Baseline and weeks 2, 4, 6 and 8 | 
| Body Temperature at Baseline and Weeks 2, 4, 6 and 8 |  | Baseline and weeks 2, 4, 6 and 8 |