Iron Deficiency Anemia (IDA)
Conditions
Keywords
Iron infusion, Non-inferiority, Ferric bepectate, Ferric carboxymaltose, Ferinject, Injectafer
Brief summary
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.
Detailed description
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.
Interventions
DRUGFerric Bepectate IV Injection
Ferric Bepectate IV Injection 50 mg iron/mL
Ferric carboxymaltose (Ferinject®) 50 mg iron/mL in two doses 7-9 days apart
Ferric carboxymaltose (Injectafer®) 50 mg iron/mL in two doses 7-9 days apart
Sponsors
AFT Pharmaceuticals, Ltd.
HungaroTrial
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, active-controlled, open-label study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in hemoglobin comparing one dose Ferric bepectate and two dose Injectafer treatment | 6 weeks | The mean change in blood hemoglobin from baseline at week 6 showing non-inferiority between the treatment groups Ferric Bepectate IV Injection (single dose) and Injectafer |
| Change in hemoglobin comparing one dose Ferric bepectate and two dose Ferinject treatment | 6 weeks | The mean change in blood hemoglobin from baseline at week 6 showing non-inferiority between the treatment groups Ferric Bepectate IV Injection (single dose) and Ferinject |
| Incidence of treatment emergent adverse events | 2 hours post infusion start | Incidence of treatment emergent adverse events (TEAE) during the 2 hours following the start of infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood hemoglobin amount | 6 weeks | Mean blood hemoglobin at weeks 1, 2, 4 and 6 timepoints. Compared between all treatment groups. |
| Hemoglobin change from baseline | 6 weeks | Mean change in blood hemoglobin from baseline to weeks 1, 2, 4 and 6. |
| Serum iron change from baseline | 6 weeks | Mean change in serum iron from baseline at weeks 1, 2, 4 and 6 timepoints. Compared between all treatment groups. |
| Serum ferritin change from baseline | 6 weeks | Mean change in serum ferritin from baseline at weeks 1, 2, 4 and 6 timepoints. Compared between all treatment groups. |
| Serum transferrin change from baseline | 6 weeks | Mean change in serum transferrin from baseline at weeks 1, 2, 4 and 6 timepoints. Compared between all treatment groups. |
| Serum transferrin saturation change from baseline | 6 weeks | Mean change in serum transferrin saturation (TSAT) from baseline at weeks 1, 2, 4 and 6 timepoints. Compared between all treatment groups. |
| Response Rate | 6 weeks | Proportion of patients with normalization (defined in WHO classification) of hemoglobin at week 6 (Response Rate). |
| Time to normalization of hemoglobin | 6 weeks | Time to normalization normalization (defined in WHO classification) of hemoglobin at week 6 (Response Rate). |
| Change in Quality of Life | 6 weeks | Treatment effect on change in Quality of Life assessed with the 36-Item Short Form Survey (SF-36) questionnaire at week 6 where a score of 0%-100% is calculated. Items are scored so that a high score defines a more favorable health state. |
| Change in fatigue symptoms | 6 weeks | Change in fatigue symptoms from baseline at week 6 measured by the Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue). A final score of 0-52 is calculated, where a high score indicates better quality of life. |
| Incidence of hypophosphatemia | 6 weeks | Incidence of hypophosphatemia (serum phosphate \< 2 mg/dL) at any time during the follow-up period (baseline - week 6) |
| Volume-corrected urine iron amount | 2 hours | Pre- and post-difference of volume-corrected urine iron levels measured before and in the first urine after the end of i.v. administration, (volume corrected iron urine is defined as the ratio between urine iron and urine creatinine) |
| Adverse event severity | 2 hours following infusion start | Severity of treatment emergent adverse events (TEAEs) during the 2 hours following infusion start |
| Adverse event incidence and severity | 6 weeks | Incidence and severity of TEAEs during the entire study period (screening - V5) |
| Treatment related adverse event incidence and severity | 6 weeks | Incidence and severity of AEs classified as possibly, probably or definitely related to the study drug (Treatment related adverse events; TRAE) during the study period (screening - V5) |
| Incidence of injection/infusion site reactions and hypersensitivity reactions | 2 hours following infusion start | Incidence of injection/infusion site reactions and hypersensitivity reactions |
| Change in serum phosphate | 6 weeks | Mean change in serum phosphate from baseline to week 6 |
| Change in serum calcium | 6 weeks | Mean change in serum calcium from baseline to week 6 |
| ECG changes | 6 weeks | Electrocardiogram (ECG) changes from baseline at week 1, 2, 4 and 6. The ECG will specifically assess the following parameters: * Heart Rate * QT interval * ST depression * T wave inversion * Prescence of tachycardia * Left ventricular hypertrophy * Investigator interpretation (normal, abnormal NCS, abnormal CS) |
| ECG and Hemoglobin relationship | 6 weeks | Relation between electrocardiogram (ECG) investigator interpretation (normal, abnormal NCS, abnormal CS) and hemoglobin at baseline and End of Treatment |
Contacts
CONTACTPhillip Aitken, PhD
STUDY_DIRECTORIoana Stanescu, Phil.Lic., MSc.
AFT Pharmaceuticals
Outcome results
None listed