Intervention: Fosfomycin
Trial phase: Phase 3
ATC code: J01XX01 | S02AA17
SMILES: C[C@@H]1O[C@@H]1P(=O)(O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 187
Group description: Participants treated with FCM given by IV injection or drip infusion

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.
Eligibility criteria:
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