Iron Deficiency Anaemia
Conditions
Keywords
IDA, Iron deficiency, iron deficiency anaemia and who are intolerant or unresponsive to oral iron therapy
Brief summary
The purpose of the trial is to evaluate and compare the effect of iron isomaltoside 1000 to iron sucrose in its ability to increase haemoglobin (Hb) in subjects with IDA when oral iron preparations are ineffective or cannot be used or where there is a clinical need to deliver iron rapidly.
Detailed description
IDA is highly prevalent in subjects with gastrointestinal diseases and cancer, menstruating or pregnant women, and subjects who have undergone bariatric procedure. IDA can have a substantial medical and quality of life (QoL) burden on the subjects and the treatment of these subjects includes controlling the bleeding and replenishing lost iron. Oral iron administration is often used in the clinical practice at many clinics; however, oral iron may not be tolerated by all subjects. Hence, there is a need for an alternative iron treatment in subjects, who do not tolerate oral iron. This study is planned to compare the efficacy and safety of iron isomaltoside 1000 with another parenteral iron preparation (iron sucrose) in subjects with IDA and who are intolerant or unresponsive to oral iron therapy or who need iron rapidly.
Interventions
DRUGiron sucrose (Venofer®)
Sponsors
BioStata
ClinStar, LLC
Laboratory Corporation of America
Pharmacosmos A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men or women \> 18 years having IDA caused by different aetiologies such as abnormal uterine bleeding, gastrointestinal diseases, cancer, bariatric procedures (gastric bypass operations), and other conditions leading to significant blood loss and with a documented history of intolerance or unresponsiveness to oral iron therapy for at least one month prior to study enrollment or where there at investigators judgment is a clinical need to deliver iron rapidly 2. Hb \< 11 g/dL 3. TSAT \< 20 % 4. S-ferritin \< 100 ng/mL 5. Willingness to participate and signing the informed consent form
Exclusion criteria
1. Anaemia predominantly caused by factors other than IDA (e.g. anaemia with untreated vitamin B12 or folate deficiency, haemolytic anaemia) 2. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemosiderosis) 3. Decompensated liver cirrhosis or active hepatitis (ALAT \> 3 times upper limit of normal) 4. Active acute or chronic infections (assessed by clinical judgement supplied with white blood cells (WBC) and C-reactive protein (CRP)) 5. Body weight \< 50 kg 6. Rheumatoid arthritis with symptoms or signs of active inflammation 7. Pregnant or nursing women. In order to avoid pregnancy, women have to be surgically sterile or use adequate contraception (e.g. intrauterine devices, hormonal contraceptives, or double barrier method) during the whole study period and after the study has ended for at least 5 times plasma biological half-life of the investigational medicinal product 8. History of multiple allergies 9. Known hypersensitivity to parenteral iron or any excipients in the investigational drug products 10. Erythropoietin treatment within 8 weeks prior to the screening visit 11. Other iron treatment or blood transfusion within 4 weeks prior to the screening visit 12. Planned elective surgery during the study 13. Participation in any other clinical study within 3 months prior to the screening 14. Any other medical condition that, in the opinion of Investigator, may cause the subject to be unsuitable for the completion of the study or place the subject at potential risk from being in the study, e.g. uncontrolled hypertension, unstable ischaemic heart disease, or uncontrolled diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With an Haemoglobin (Hb) Increase of ≥ 2 g/dL From Baseline at Any Time From Week 1 to Week 5 | From baseline to week 5 | The primary efficacy endpoint of the trial was the count of subjects with an Hb increase of ≥ 2 g/dL from baseline at any time from week 1 to week 5. 'Any time' implied that if the endpoint was met at a time-point prior to or at week 5, the effect (increase of ≥ 2 g/dL) did not have to be maintained throughout the trial in order for a subject to be a responder. Number of responders (i.e. a subject with increase in Hb ≥ 2 g/dL from baseline at any time from week 1 to week 5) and percentages according to number of subjects in the analysis set were summarised. |
Secondary
| Measure | Time frame |
|---|---|
| Change in Hb Concentration | From baseline to week 2, 4 and 5 |
| Change in Serum (s)-Ferritin Concentration | From baseline to week 1, 2, 4, and 5 |
| Change in Transferrin Saturation (TSAT) | From baseline to week 1, 2, 4, and 5 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Iron Isomaltoside 1000 (Monofer®) iron isomaltoside 1000 (Monofer®)
iron isomaltoside 1000 (Monofer®) | 342 |
| Iron Sucrose (Venofer®) iron sucrose (Venofer®)
iron sucrose (Venofer®) | 169 |
| Total | 511 |
Baseline characteristics
| Characteristic | Iron Isomaltoside 1000 (Monofer®) | Iron Sucrose (Venofer®) | Total |
|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 15.8 | 46.8 years STANDARD_DEVIATION 14.9 | 48.4 years STANDARD_DEVIATION 15.6 |
| Region of Enrollment United States | 342 participants | 169 participants | 511 participants |
| Sex: Female, Male Female | 309 Participants | 154 Participants | 463 Participants |
| Sex: Female, Male Male | 33 Participants | 15 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 333 | 0 / 168 |
| other Total, other adverse events | 100 / 333 | 54 / 168 |
| serious Total, serious adverse events | 11 / 333 | 6 / 168 |
Outcome results
Primary
Number of Subjects With an Haemoglobin (Hb) Increase of ≥ 2 g/dL From Baseline at Any Time From Week 1 to Week 5
The primary efficacy endpoint of the trial was the count of subjects with an Hb increase of ≥ 2 g/dL from baseline at any time from week 1 to week 5. 'Any time' implied that if the endpoint was met at a time-point prior to or at week 5, the effect (increase of ≥ 2 g/dL) did not have to be maintained throughout the trial in order for a subject to be a responder. Number of responders (i.e. a subject with increase in Hb ≥ 2 g/dL from baseline at any time from week 1 to week 5) and percentages according to number of subjects in the analysis set were summarised.
Time frame: From baseline to week 5
Population: Full analysis set (FAS) (N = 491): The FAS consisted of all subjects who were randomised, received at least one dose of the trial drug, and had at least one post-baseline Hb assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iron Isomaltoside 1000 (Monofer®) | Number of Subjects With an Haemoglobin (Hb) Increase of ≥ 2 g/dL From Baseline at Any Time From Week 1 to Week 5 | 226 participants |
| Iron Sucrose (Venofer®) | Number of Subjects With an Haemoglobin (Hb) Increase of ≥ 2 g/dL From Baseline at Any Time From Week 1 to Week 5 | 83 participants |
Secondary
Change in Hb Concentration
Time frame: From baseline to week 2, 4 and 5
Population: FAS (N = 491): The FAS consisted of all subjects who were randomised, received at least one dose of the trial drug, and had at least one post-baseline Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside 1000 (Monofer®) | Change in Hb Concentration | Week 2 | 1.56 g/dL | Standard Deviation 1.03 |
| Iron Isomaltoside 1000 (Monofer®) | Change in Hb Concentration | Week 4 | 2.35 g/dL | Standard Deviation 1.32 |
| Iron Isomaltoside 1000 (Monofer®) | Change in Hb Concentration | Week 5 | 2.52 g/dL | Standard Deviation 1.41 |
| Iron Sucrose (Venofer®) | Change in Hb Concentration | Week 2 | 0.87 g/dL | Standard Deviation 0.9 |
| Iron Sucrose (Venofer®) | Change in Hb Concentration | Week 4 | 1.74 g/dL | Standard Deviation 1.17 |
| Iron Sucrose (Venofer®) | Change in Hb Concentration | Week 5 | 2.05 g/dL | Standard Deviation 1.27 |
Secondary
Change in Serum (s)-Ferritin Concentration
Time frame: From baseline to week 1, 2, 4, and 5
Population: FAS (N = 491): The FAS consisted of all subjects who were randomised, received at least one dose of the trial drug, and had at least one post-baseline Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside 1000 (Monofer®) | Change in Serum (s)-Ferritin Concentration | Week 1 | 431.2 ng/mL | Standard Deviation 221.4 |
| Iron Isomaltoside 1000 (Monofer®) | Change in Serum (s)-Ferritin Concentration | Week 2 | 516.6 ng/mL | Standard Deviation 268.1 |
| Iron Isomaltoside 1000 (Monofer®) | Change in Serum (s)-Ferritin Concentration | Week 4 | 285.3 ng/mL | Standard Deviation 205.2 |
| Iron Isomaltoside 1000 (Monofer®) | Change in Serum (s)-Ferritin Concentration | Week 5 | 241.2 ng/mL | Standard Deviation 209.3 |
| Iron Sucrose (Venofer®) | Change in Serum (s)-Ferritin Concentration | Week 5 | 185.7 ng/mL | Standard Deviation 166.8 |
| Iron Sucrose (Venofer®) | Change in Serum (s)-Ferritin Concentration | Week 1 | 86.9 ng/mL | Standard Deviation 84.8 |
| Iron Sucrose (Venofer®) | Change in Serum (s)-Ferritin Concentration | Week 4 | 195.0 ng/mL | Standard Deviation 126.2 |
| Iron Sucrose (Venofer®) | Change in Serum (s)-Ferritin Concentration | Week 2 | 126.2 ng/mL | Standard Deviation 87.2 |
Secondary
Change in Transferrin Saturation (TSAT)
Time frame: From baseline to week 1, 2, 4, and 5
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iron Isomaltoside 1000 (Monofer®) | Change in Transferrin Saturation (TSAT) | Week 1 | 15.7 percent | Standard Deviation 9.6 |
| Iron Isomaltoside 1000 (Monofer®) | Change in Transferrin Saturation (TSAT) | Week 4 | 16.3 percent | Standard Deviation 9 |
| Iron Isomaltoside 1000 (Monofer®) | Change in Transferrin Saturation (TSAT) | Week 2 | 17.9 percent | Standard Deviation 9.8 |
| Iron Isomaltoside 1000 (Monofer®) | Change in Transferrin Saturation (TSAT) | Week 5 | 15.6 percent | Standard Deviation 8.6 |
| Iron Sucrose (Venofer®) | Change in Transferrin Saturation (TSAT) | Week 5 | 11.8 percent | Standard Deviation 9.5 |
| Iron Sucrose (Venofer®) | Change in Transferrin Saturation (TSAT) | Week 1 | 3.3 percent | Standard Deviation 8.1 |
| Iron Sucrose (Venofer®) | Change in Transferrin Saturation (TSAT) | Week 2 | 5.7 percent | Standard Deviation 6.8 |
| Iron Sucrose (Venofer®) | Change in Transferrin Saturation (TSAT) | Week 4 | 11.5 percent | Standard Deviation 9.5 |