A Study to Test the Non-Inferiority of Ferric Bepectate IV Against Ferric Carboxymaltose in Patients With Iron Deficiency Anemia

A Multicentre, Prospective, Randomized, Active-Controlled, Open-Label, Phase III Study to Test the Non-Inferiority of Intravenous Injection of Ferric Bepectate IV Injection Compared to Ferric Carboxymaltose for Treatment of Patients With Iron Deficiency Anaemia (IDA)

The goal of this clinical trial is to see if a new intravenous iron formulation (Ferric Bepectate IV Injection) can treat adult patients with iron deficiency anemia (IDA) by increasing blood hemoglobin (Hb) as an established formulation (Ferric carboxymaltose). It will also learn about the safety of Ferric Bepectate IV Injection. The main questions it aims to answer are:

• Does hemoglobin increase by the same amount 6 weeks after each treatment?
• What medical problems do participants have when being treated with the drug? Researchers will compare single dose treatment plans of Ferric Bepectate to double dose treatment plans of both Ferric Bepectate and Ferric carboxymaltose.

Participants and researchers will know which drug they are being provided (open-label). Participants will visit the clinic 5 times over 6 weeks for checkups, blood tests and questionaries. The first two visits will be seven days apart and include the two doses of iron treatment.

Iron is essential for the normal functioning of a human body. Iron deficiency anemia (IDA) occurs when blood lacks adequate healthy red blood cells, preventing adequate distribution of oxygen throughout the tissue of the body.

IDA, if left uncorrected, may result in complications such as extreme fatigue, weakness, chest pain, shortness of breath, irregular heartbeats or even heart failure in some cases, in addition to reducing the overall quality of life of a patient. Iron supplementation can effectively treat IDA. An iron-rich diet is known to enhance iron levels, however supplementation is limited by the bio-availability of iron compounds. Oral iron treatment is the most common form of therapy for iron supplementation. However, oral iron supplementation is not ideal for all patients, as adverse events are common, and some patients also fail to respond. Common adverse events (AEs) include significant gastrointestinal discomfort, metallic taste and staining of teeth, resulting in patience discontinuing the treatment. Intravenous (i.v) iron therapy is regarded as a safe method to correct anemia resulting from several conditions that avoids many of the gastrointestinal AEs common with oral iron supplementation.

Ferric carboxymaltose is an established i.v iron formulation approved to treat IDA in Europe and USA. In patients with high iron need, ferric carboxymaltose requires at least two injections, at least 7 days apart. A new i.v. iron formulation has been developed, Ferric Bepectate IV Injection. Ferric Bepectate IV Injection has the potential to be dosed at higher volumes compared to other i.v. iron formulations, allowing for patients with high iron needs to only undergo a single infusion, reducing the medical burden on both the patient and the medical system, and providing a rapid improvement to IDA and associated symptoms.

The current phase 3 study aims to compare Ferric Bepectate IV Injection with two Ferric carboxymaltose formulations (comparators: Ferinject® and Injectafer®) to determine non-inferiority between the Ferric Bepectate IV Injection single dose administration and the current approved dosing for the comparators. A comparison between treatments of the change of hemoglobin (Hb) from baseline after 6 weeks will be the primary outcome. Safety of each treatment will also be assessed to determine superiority, by examining the number of adverse events in the 2 hour period following the beginning of infusion. Key secondary safety endpoints will assess the difference in volume-corrected urine iron after i.v administration, and incidence of hypophosphatemia during the 6 week follow-up period.

A two-dose administration of Ferric Bepectate IV Injection will also be assessed to compare efficacy, tolerance, and safety with the single-dose administration and the comparators.

Inclusion Criteria:

1. Male or female patient at least 18 years old at the time of screening
2. Patients with general iron deficiency anaemia IDA
3. Patients with serum ferritin levels ≤40 ng/mL inclusive
4. Patients with haemoglobin (Hb) levels <10 g/dL
5. Patients ≥ 35 kg body weight
6. The patient has adequate hepatic and renal function defined as a serum aspartate aminotransferase or alanine aminotransferase level that are no more than 3 times the upper limit of the normal range, a serum bilirubin level that is no more than 2 times the upper limit of the normal range and a serum creatinine level of less than 2 mg/dL.
7. The patient is able to understand the protocol and provides informed consent to participate in the study

Exclusion Criteria:

1. Pregnant or breastfeeding patients

2. Female patients not willing to use a safe method of contraception (PEARL index <1) for the full study (screening - V5).

3. Severe physical inability, e.g., ASA physical status IV or V.

4. Non-iron deficiency anaemia, e.g., known Vitamin B12 or folate deficiency, hemoglobinopathy, or unexplained anaemia.

5. Patients with life-threatening anaemia, defined as Hb < 6.5 g/dL.

6. Patient is expected to require a blood transfusion within the study period or has had a blood transfusion within the 30 days prior screening.

7. Anticipated medical need for erythropoiesis-stimulating agents during the study period (screening - V5).

8. Patients with hemodynamic instability due to any ongoing bleeding. Absence of ongoing bleeding will be confirmed either by decision of two independent physicians or by removal of drainage whichever occurs earlier in routine care.

9. Patient has undergone a surgical procedure during the 30 days prior to screening, and/or is expected to undergo a surgical procedure during the study period (screening - V5).

10. Patients with any contraindication to the investigational products, e.g.,

    1. known sensitivity to iron or an ingredient of the investigational products,
    2. significant history of systemic allergic reactions,
    3. hemochromatosis, thalassemia or TSAT >50% as indicator of iron overload,
    4. acute or chronic intoxication,
    5. infection (patient on non-prophylactic antibiotics),
    6. chronic liver disease and/or screening ALT or AST above three times the upper limit of the normal range.
    7. chronic kidney disease, defined as GFR <30 mL/min.

11. Primary hematologic disease.

12. Drug or alcohol abuse according to WHO definition.

13. Potentially unreliable patients, and those judged by the investigator to be unsuitable for the study.

14. Current or previous participation in another clinical trial during the last 90 days before screening.

15. Exclusion criteria according to SmPC of Ferric Carboxymaltose.

16. The following concomitant treatments prescribed by a physician for non-iron deficiency anaemia (e.g., known vitamin B12 or folate deficiency), hemoglobinopathy, or unexplained anaemia are not allowed during the study and 24 weeks before screening: Erythropoiesis-stimulating agents, vitamin B12, Folic acid or other I.V. or oral iron products.

17. Estimated life expectancy of <6 months or, for cancer patients, an Eastern Cooperative Oncology Group performance status >1