A phase 3 randomized, open-label (sponsor-blind), active-controlled, parallel-group, multi-center, event driven study in dialysis subjects with anemia associated with chronic kidney disease to evaluate the safety and efficacy of daprodustat compared to recombinant human erythropoietin, following a switch from erythropoietin-stimulating agents.;Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Dialysis (ASCEND-D)<br>

Phase 3

Completed

• Conditions: Anemia; chronic kidney disease; 10038430

• Registration Number: NL-OMON50208
• Lead Sponsor: GlaxoSmithKline

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 16

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the
following criteria apply at screening (Week -8) and randomization (Day 1)
unless otherwise specified.
1. Age (confirm at screening only): 18 to 99 years of age (inclusive).
2. ESAs: Use of any approved ESA for at least the 6 weeks prior to screening
and between screening and randomization.
3. Hgb concentration measured by HemoCue (range is specified in protocol)
4. Dialysis: On dialysis > 90 days prior to screening and continuing on the
same mode of dialysis from screening (Week -8) through to randomization (Day 1).
5. Frequency of Dialysis:
* - HD: *2 times/week
* - PD: * 5 times/week
* - Home HD: (*2times/week)
6. Compliance with placebo [randomization (Day 1) only]: *80% and * 120%
compliance with placebo during run-in period (NOTE: this is in addition to ESA
treatment).
7. Informed consent (screening only): capable of giving signed informed consent
which includes compliance with the requirements and restrictions listed in the
consent form and in this protocol.

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the
following criteria apply at screening (Week -8) or randomization (Day 1),
unless otherwise specified.
CKD related criteria
1. Kidney transplant: Planned living-related or living-unrelated kidney
transplant within 52 weeks after study start (Day 1).
Anemia related criteria
2. Ferritin (screening only): *100 ng/mL (*100 ug/L).
3. Transferrin saturation (TSAT) (screening only): *20%. If TSAT is 18-20%,
then a retest using a new blood sample can be obtained within 7 days of the
final laboratory report; the final retest value must be >20% to confirm
eligibility.
4. Aplasias: History of bone marrow aplasia of pure red cell aplasia.
5. Other causes of anemia: Untreated pernicious anemia, thalassemia major,
sickle cell disease or myelodysplastic syndrome.
6. Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric,
duodenal, or esophageal ulcer disease OR clinically significant GI bleeding *4
weeks prior to screening through to randomization (Day 1).
CV disease-related criteria
7. MI or acute coronary syndrome: *4 weeks prior to screening through to
randomization (Day 1).
8. Stroke or transient ischemic attack: *4 weeks prior to screening through to
randomization (Day 1).
9. Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart
Association (NYHA) functional classification system.
10. Current uncontrolled hypertension: Current uncontrolled hypertension as
determined by the investigator that would contraindicate the use of rhEPO.
11. QTcB (Day 1): QTcB >500 msec, or QTcB >530 msec in subjects with bundle
branch block. There is no QTc exclusion for subjects with a predominantly
ventricular paced rhythm.
Other disease-related criteria
12. Liver disease: (any one of the following):
- Alanine transaminase (ALT) >2x upper limit of normal (ULN) (screening only)
- Bilirubin >1.5xULN (screening only)
NOTE: Isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated
and direct bilirubin <35%.
- Current unstable liver or biliary disease per investigator assessment,
generally by the presence of ascites,
encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices,
persistent jaundice, or cirrhosis.
NOTE: Stable chronic liver disease (including asymptomatic gallstones, chronic
hepatitis B or C, or Gilbert's syndrome) are acceptable if subject otherwise
meets entry criteria.
13. Malignancy: History of malignancy within the 2 years prior to screening
through to randomization (Day 1) or currently receiving treatment for cancer,
or complex kidney cyst (e.g. Bosniak Category II F, III or IV) > 3cm. Note: The
only exception is localized squamous cell or basal cell carcinoma of the skin
that has been definitively treated 4 weeks prior to screening.
Concomitant medication and other randomized treatment-related criteria 14.
Severe allergic reactions: History of severe allergic or anaphylactic reactions
or hypersensitivity to excipients in the investigational product
(refer to daprodustat IB), or epoetin alfa or darbepoetin alfa (refer to
product labeling).
15. Drugs and supplements Use of strong inhibitors of CYP2C8 (e.g.,
gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin).
16. Other study participation: Use of other investi

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Time to first occurrence of adjudicated major adverse cardiovascular event<br /><br>(MACE) [composite of all-cause mortality, non-fatal myocardial infarction (MI)<br /><br>and non-fatal stroke]<br /><br>- Mean change in Hgb between baseline and evaluation period (EP, mean over<br /><br>Weeks 28 to 52)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Time to first occurrence of adjudicated<br /><br>-MACE<br /><br>-MACE or a thromboembolic event (vascular access thrombosis, deep vein<br /><br>thrombosis or pulmonary embolism)<br /><br>-MACE or a hospitalization for heart failure (HF)<br /><br>Average monthly IV iron dose (mg)/subject to Week 52<br /><br><br /><br>Safety:<br /><br>-Incidence and severity of AEs and serious adverse events (SAEs) including AEs<br /><br>of special interest<br /><br>-Reasons for discontinuation of study treatment<br /><br>-Absolute values and changes from baseline in laboratory parameters, BP and<br /><br>heart rate (HR)</p><br>