Iron Deficiency Anemia, Chronic Kidney Disease
Conditions
Brief summary
The study is designed to determine the effects of an investigational drug Monofer in subjects with non-dialysis dependent chronic kidney disease (NDD-CKD) subjects and with iron deficiency anaemia (IDA).
Interventions
DRUGMonofer
Infusion or injections
DRUGIron Sulphate
Oral intake
Sponsors
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 and women, aged more than 18 years. 2. Subjects diagnosed with NDD-CKD with MDRD calculated eGFR between 15-59 mL/min. 3. Hb \< 11.0 g/dL (6.80 mmol/L) 4. Either or both of the following iron stores indicators below target {Serum ferritin \< 100 ug/l and Transferrin saturation (TfS)\<20%}. 5. Life expectancy beyond 12 months by Principal Investigator's judgement. 6. Willingness to participate after informed consent and any authorization as required by local law ( e.g. Protected Health Information \[PHI\] for North America).
Exclusion criteria
1. Anaemia predominantly caused by factors other than renal impairment or iron deficiency (according to Principal Investigator's judgment). 2. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemosiderosis). 3. Drug hypersensitivity (i.e. previous hypersensitivity to Iron Dextran or iron mono- or disaccharide complexes or to iron sulphate or any excipients of the study drug. 4. Subjects with history of multiple allergies. 5. Decompensated liver cirrhosis or active hepatitis (Alanine Aminotransferase (ALT) \> 3 times upper normal limit). 6. Active acute or chronic infections ((assessed by clinical judgment), supplied with White Blood Cells (WBC) and C-Reactive Protein (CRP)). 7. Rheumatoid arthritis with symptoms or signs of active joint inflammation. 8. Pregnancy and nursing (To avoid pregnancy, women have to be postmenopausal (at least 12 months must have elapsed since last menstruation), surgically sterile, or women of child bearing potential must use one of the following contraceptives 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 (5 days): Contraceptive pills, intrauterine devices (IUD), contraceptive depot injections (prolonged-release gestagen), subdermal implantation, vaginal ring, and transdermal patches). 9. Extensive active bleeding necessitating blood transfusion. 10. Planned elective surgery during the study. 11. Participation in any other clinical study within 3 months prior to screening. 12. Known intolerance to oral iron treatment. 13. Untreated B12 or folate deficiency. 14. I.V. or oral iron treatment or blood transfusion within 4 weeks prior to screening visit. 15. ESA treatment within 8 weeks prior to screening visit. 16. Serum ferritin \> 500 µg/L. 17. Any other medical condition that, in the opinion of Principal 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 or interfere with study drug evaluation. Example, Uncontrolled Hypertension, Unstable Ischemic Heart Disease or Uncontrolled Diabetes Mellitus. 18. Body weight \< 30 kilograms.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Hemoglobin (Hb) Concentration From Baseline to Week 4. | Baseline, 4 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in Hemoglobin Concentration From Baseline to Week 8 | Baseline to week 8 |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Monofer Injections or infusions
Monofer: Infusion or injections | 233 |
| Iron Sulphate Oral intake
Iron Sulphate: Oral intake | 118 |
| Total | 351 |
Baseline characteristics
| Characteristic | Monofer | Iron Sulphate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 69 Participants | 38 Participants | 107 Participants |
| Age, Categorical Between 18 and 65 years | 164 Participants | 80 Participants | 244 Participants |
| Region of Enrollment Austria | 16 participants | 5 participants | 21 participants |
| Region of Enrollment Denmark | 13 participants | 6 participants | 19 participants |
| Region of Enrollment Germany | 20 participants | 11 participants | 31 participants |
| Region of Enrollment India | 138 participants | 64 participants | 202 participants |
| Region of Enrollment Poland | 4 participants | 4 participants | 8 participants |
| Region of Enrollment Russian Federation | 9 participants | 8 participants | 17 participants |
| Region of Enrollment Sweden | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United Kingdom | 19 participants | 12 participants | 31 participants |
| Region of Enrollment United States | 13 participants | 8 participants | 21 participants |
| Sex: Female, Male Female | 141 Participants | 54 Participants | 195 Participants |
| Sex: Female, Male Male | 92 Participants | 64 Participants | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 48 / 228 | 22 / 117 |
| serious Total, serious adverse events | 12 / 228 | 10 / 117 |
Outcome results
Primary
Change in Hemoglobin (Hb) Concentration From Baseline to Week 4.
Time frame: Baseline, 4 weeks
Population: The FAS population included all the subjects who were randomised into the study, received at least one dose of the study drug, and had at least one post-baseline Hb assessment. The subjects were considered as randomised, regardless of which treatment they actually received.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Monofer | Change in Hemoglobin (Hb) Concentration From Baseline to Week 4. | 0.57 g/dL |
| Iron Sulphate | Change in Hemoglobin (Hb) Concentration From Baseline to Week 4. | 0.35 g/dL |
Secondary
Change in Hemoglobin Concentration From Baseline to Week 8
Time frame: Baseline to week 8
Population: The FAS population included all the subjects who were randomised into the study, received at least one dose of the study drug, and had at least one post-baseline Hb assessment. The subjects were considered as randomised, regardless of which treatment they actually received.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Monofer | Change in Hemoglobin Concentration From Baseline to Week 8 | 0.92 g/dL |
| Iron Sulphate | Change in Hemoglobin Concentration From Baseline to Week 8 | 0.45 g/dL |