A phase 3 randomized, open-label (sponsor-blind), active-controlled, parallel-group, multi-center, event driven study in non-dialysis subjects with anemia associated with chronic kidney disease to evaluate the safety and efficacy of daprodustat compared to darbepoetin alfa;Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Non-Dialysis (ASCEND-ND)
- Conditions
- Anemiachronic kidney disease10038430
- Registration Number
- NL-OMON50351
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
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.CKD stage (confirm at screening only): Kidney
Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by
eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula [Levey, 2009].,
3.ESAs: , *Group 1 (not using ESAs): No ESA use within the 6 weeks prior to
screening and no ESA use between screening and randomization (Day 1)., *Group 2
(ESA users): Use of any approved ESA (see footnote in protocol) for the 6 weeks
prior to screening and continuing between screening and randomization.,
4.HemoCue Hgb (range is specified in protocol): Hgb defined by ESA use,
5.Compliance with placebo [randomization (Day 1) only]: *80% and *120%
compliance with placebo during run-in period (NOTE: for ESA users, this is in
addition to ESA treatment)., 6.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.
A subject will not be eligible for inclusion in this study if any of the
following criteria apply at screening (Week -8) and randomization (Day 1),
unless otherwise specified. , CKD related criteria, 1.Dialysis: On dialysis
or clinical evidence of impending need to initiate dialysis within 90 days
after study start (Day 1)., 2.Kidney transplant: Planned living-related or
living-unrelated kidney transplant within 52 weeks after study start (Day 1).,
Anemia-related criteria, 3.Ferritin (screening only): *100 ng/mL (*100 ug/L).,
4.Transferrin saturation (TSAT) (screening only): *20%. If the laboratory
report indicates TSAT is 18-20%, then up to two retests can be obtained using a
new blood sample. These retests may occur during screening and run-in up to two
weeks prior to anticipated randomization (Day 1); the final retest value must
be >20% to confirm eligibility., 5.Aplasias: History of bone marrow aplasia or
pure red cell aplasia., 6.Other causes of anemia: Untreated pernicious anemia,
thalassemia major, sickle cell disease or myelodysplastic syndrome.,
7.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, 8.MI or acute coronary syndrome: *4 weeks prior to screening through
to randomization (Day 1)., 9.Stroke or transient ischemic attack: *4 weeks
prior to screening through to randomization (Day 1)., 10.Heart failure (HF):
Chronic Class IV HF, as defined by the New York Heart Association (NYHA)
functional classification system., 11.Current uncontrolled hypertension:
Current uncontrolled hypertension as determined by the investigator., 12.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, 13.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 defined 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.,
14.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,
15.Severe allergic reactions: History of severe allergic or anaphylactic
reactions or hypersensitivity to excipients in the investigational product
(refer to daprodustat IB) or darbepoetin alfa (refer to product label
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><br /><br>Time to progression of CKD<br /><br><br /><br>Veiligheid:<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 randomized treatment<br /><br>-Absolute values and changes from baseline</p><br>