Phase 2
N=15
Anemia Studies in CKD: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat- Iron (ASCEND: Fe)
Anaemia
Bottom Line
View on ClinicalTrials.gov: NCT03457701 ↗Enrolled (actual)
15
Serious AEs
7.1%
Results posted
Jul 2023
Primary outcome: Primary: Percentage of Fractional Oral Iron Absorption Following Treatment With Daprodustat and rhEPO — 20.64; 20.62 Percentage (%) of iron absorbed — p=0.9971
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Daprodustat (Drug); rhEPO (Drug); Ferrous sulfate containing the stable iron isotope (57Fe) (Drug); Ferrous sulfate containing the stable iron isotope (58Fe) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jul 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Fractional Oral Iron Absorption Following Treatment With Daprodustat and rhEPO |
20.64; 20.62 | 0.9971 |
| SECONDARY Periods 1 and 2: Change From Baseline in Serum Iron Following Treatment With Daprodustat and rhEPO |
-1.5; 1.7; 2.5; 3.3; -1.3; -3.5 | — |
| SECONDARY Period 1 and 2: Change From Baseline in Transferrin Following Treatment With Daprodustat or rhEPO |
0.182; 0.145; 0.283; -0.040; -0.177; -0.163 | — |
| SECONDARY Periods 1 and 2: Change From Baseline in Transferrin Saturation Following Treatment With Daprodustat or rhEPO |
-5.2; 3.5; 3.0; 8.2; -5.5; -4.8 | — |
| SECONDARY Periods 1 and 2: Change From Baseline in Soluble Transferrin Receptor Following Treatment of Daprodustat and rhEPO |
-0.218; 0.063; -0.340; -0.015; -0.338; 0.227 | — |
| SECONDARY Periods 1 and 2: Ratio to Baseline in Ferritin Following Treatment With Daprodustat and rhEPO |
1.126; 0.937; 1.109; 1.004; 1.067; 0.957 | — |
| SECONDARY Periods 1 and 2: Ratio to Baseline (Day 1) in Hepcidin Following Treatment With Daprodustat and rhEPO |
0.860; 0.904; 0.916; 1.052; 0.703; 1.201 | — |
| SECONDARY Periods 1 and 2: Change From Baseline in Erythroferrone Following Treatment With Daprodustat and rhEPO |
0.135; -0.062; 0.075; -0.090; 0.063; -0.068 | — |
| SECONDARY Periods 1 and 2: Change From Baseline in Hemoglobin Following Treatment With Daprodustat and rhEPO |
0.7; 2.8; -5.0; 3.5; -5.3; 3.7 | — |
| SECONDARY Periods 1 and 2: Change From Baseline in Hematocrit Following Treatment With Daprodustat and rhEPO |
0.002; 0.011; -0.017; 0.009; -0.006; 0.009 | — |
| SECONDARY Periods 1 and 2: Change From Baseline in Erythrocytes Following Treatment With Daprodustat and rhEPO |
0.05; 0.13; -0.13; 0.13; -0.17; 0.13 | — |
| SECONDARY Periods 1 and 2: Change From Baseline in Erythrocyte Mean Corpuscular Volume Following Treatment With Daprodustat and rhEPO |
-0.8; -0.5; -1.5; -0.8; 2.8; -0.3 | — |
| SECONDARY Periods 1 and 2: Change From Baseline in Reticulocyte Hemoglobin Following Treatment of Daprodustat and rhEPO |
0.333; -0.033; 0.250; 0.717; 0.817; -0.350 | — |
| SECONDARY Periods 1 and 2: Change From Baseline in Reticulocytes Following Treatment With Daprodustat and rhEPO |
0.001; 0.002; 0.004; -0.004; 0.004; -0.005 | — |
Summary
Daprodustat administration has the potential, by virtue of increasing hypoxia-inducible factor (HIF) levels, to increase oral iron absorption and incorporation into hemoglobin (Hgb). Therefore, the purpose of this study is to compare the effect of daprodustat to rhEPO (i.e., epoetin alfa or darbepoetin alfa) on non-heme oral iron absorption using stable isotopic iron (57Fe and 58Fe) by measuring incorporation of iron in erythrocytes. This study will be a randomized, repeat dose, open label, two period cross-over study in adult, male and female participants with anemia associated with chronic kidney disease who are not on dialysis currently treated with stable doses less than or equal to (<=) 50 percent (%) change in 4-weekly dose) for at least 8 weeks prior to and including the screening period, of rhEPO (i.e., epoetin alfa or darbepoetin alfa). Sufficient participants will be enrolled such that at least 12 participants comprise the Evaluable Population. The study will compare the fractional iron absorption between treatment arms (daprodustat and rhEPO [i.e., epoetin alfa or darbepoetin alfa]) and will evaluate the difference is equal/not equal to zero.
Eligibility Criteria
Inclusion Criteria
- Participants must be at least 18 years of age inclusive, at the time of signing the informed consent.
- Participants who are Stage 3, 4 or 5 Chronic kidney disease (CKD) (confirmed at Week-4 only) defined by estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
- Participants who are currently treated with stable doses ( =20 microgram per milliliter (μg/mL) at screening.
- Myocardial infarction or acute coronary syndrome: 500 milliseconds (msec), or QTcB > 530 msec in participants with Bundle Branch Block. There is no corrected QT interval (QTc) exclusion for participants with a predominantly paced rhythm.
- Active chronic inflammatory disease that could impact erythropoiesis.
- History of bone marrow aplasia or pure red cell aplasia.
- Conditions, other than anemia associated with chronic kidney disease, which can affect erythropoiesis.
- Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease OR clinically significant gastrointestinal (GI) bleeding from 2 times upper limit of normal (ULN; screening only); Bilirubin >1.5 times ULN (screening only). Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Major surgery (excluding vascular access surgery) within the 8 weeks prior to screening through Day 1, or planned during the study.
- Blood transfusion within 8 weeks prior to screening through Day 1, or an anticipated need for blood transfusion during the study.
- Clinical evidence of an acute infection, or history of infection requiring IV antibiotic therapy from 4 weeks prior to screening through Day 1.
- History of malignancy within the two years prior to screening through Day 1 or currently receiving treatment for cancer, with the exception of localized squamous cell or basal cell carcinoma of the skin definitively treated 12 weeks prior to Day 1.
- Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
Data sourced from ClinicalTrials.gov (NCT03457701). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.