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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03029208




Registration number
NCT03029208
Ethics application status
Date submitted
20/01/2017
Date registered
24/01/2017
Date last updated
8/07/2020

Titles & IDs
Public title
Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-in Incident Dialysis (ASCEND-ID)
Scientific title
A 52-week Open-label (Sponsor-blind), Randomized, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Efficacy and Safety of Daprodustat Compared to Recombinant Human Erythropoietin in Subjects With Anemia Associated With Chronic Kidney Disease Who Are Initiating Dialysis
Secondary ID [1] 0 0
2016-000507-86
Secondary ID [2] 0 0
201410
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaemia 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Blood 0 0 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Daprodustat
Treatment: Drugs - Darbepoetin alfa
Treatment: Drugs - Iron therapy

Experimental: Daprodustat treated anemic subjects - Subjects will receive oral daprodustat once daily.

Active Comparator: Darbepoetin alfa treated anemic subjects - Subjects will receive darbepoetin alfa subcutaneously or intravenously.


Treatment: Drugs: Daprodustat
Daprodustat will be supplied as film coated tablets for oral administration containing 1, 2, 4, 6, 8, or 10 mg of daprodustat. Doses of 12, 16, and 24 mg of daprodustat will be provided using multiples of these tablet strengths.

Treatment: Drugs: Darbepoetin alfa
Darbepoetin alfa will be supplied as prefilled syringes (PFS) for SC/IV injection available in strengths: 20, 30, 40, 60, 80, 100 and 150 mcg.

Treatment: Drugs: Iron therapy
Iron therapy will be administered if ferritin is <=100 ng/mL and/or TSAT is <=20%.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean change from Baseline in hemoglobin (Hgb) during evaluation period (EP) - The Baseline Hgb will be the value obtained on Day 1. The EP is defined as the period from the end of the stabilization period (Week 28) to Week 52.
Timepoint [1] 0 0
Randomization (Day 1) to Week 52
Secondary outcome [1] 0 0
Average monthly IV iron dose milligrams (mg) per subject from Baseline to Week 52 - IV iron use for all subjects will be recorded and the average monthly IV iron dose up to week 52 while on treatment will be calculated.
Timepoint [1] 0 0
Randomization (Day 1) to Week 52
Secondary outcome [2] 0 0
Change from Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52 - SBP and DBP will be measured at each study visit. Change from Baseline will be calculated as post dose value minus Baseline value.
Timepoint [2] 0 0
Randomization (Day 1) to Week 52
Secondary outcome [3] 0 0
Number of BP exacerbation events per 100 patient years - SBP and DBP will be measured at each study visit.
Timepoint [3] 0 0
Up to Week 58
Secondary outcome [4] 0 0
Number (%) of subjects with at least one BP exacerbation event during study - SBP and DBP will be measured at each study visit.
Timepoint [4] 0 0
Up to Week 58
Secondary outcome [5] 0 0
Change from Baseline in Hgb up to Week 52 - Change from Baseline will be calculated as post dose value minus Baseline value.
Timepoint [5] 0 0
Baseline and up to Week 52
Secondary outcome [6] 0 0
Number (%) of Hgb responders - Responders will be defined as subjects with mean Hgb within Hgb analysis range during the EP
Timepoint [6] 0 0
Week 28 to Week 52
Secondary outcome [7] 0 0
Percentage time for which Hgb is in analysis range during the EP - Analysis range is from 10-11.5 g/dL.
Timepoint [7] 0 0
Week 28 to Week 52
Secondary outcome [8] 0 0
Time to rescue - Rescue is defined as permanently stopping randomized treatment due to meeting rescue criteria.
Timepoint [8] 0 0
Up to Week 52
Secondary outcome [9] 0 0
Change in short form (SF)-36 health-related quality of life (HRQOL) scores - Mean change in SF-36 HRQOL score between Baseline and Weeks 8, 12, 28, 52 will be determined.
Timepoint [9] 0 0
Baseline and up to Week 52
Secondary outcome [10] 0 0
Change from Baseline in Health Utility EuroQol five dimensions five level (EQ-5D-5L) questionnaire score at Week 52 - Change from Baseline in EQ-5D-5L score at Week 52.
Timepoint [10] 0 0
Baseline and Week 52
Secondary outcome [11] 0 0
Change from Baseline in EQ visual analogue scale (VAS) at Week 52 - Change from Baseline in EQVAS at Week 52.
Timepoint [11] 0 0
Baseline and Week 52
Secondary outcome [12] 0 0
Change from Baseline in the CKD- Anemia Symptoms Questionnaire (AQ) - Change from Baseline to Week 52 by domain and overall symptom score.
Timepoint [12] 0 0
Baseline and Week 52
Secondary outcome [13] 0 0
Change from Baseline in patient global impression of severity (PGI-S) - Change from Baseline to Week 52 in symptom severity score.
Timepoint [13] 0 0
Baseline and up to Week 52
Secondary outcome [14] 0 0
Summary of pharmacokinetic parameters of plasma daprodustat and three major metabolites in dialysis subjects - Pharmacokinetic parameters that is, pre-dose trough (Ctau) and maximum observed concentration (Cmax) of daprodustat and three major metabolites (M2, M3 and M13).
Timepoint [14] 0 0
Predose, 0.5, 1, 2, and 3 hours post dose at Week 4, 8 or 12

Eligibility
Key inclusion criteria
- 18 to 99 years of age inclusive.

- Planning to start chronic dialysis within the next 6 weeks (from the date of the
screening visit) OR have started and received dialysis (as specified below) for
end-stage renal disease for a maximum of <=90 days immediately prior to randomization
and is not expected to stop dialysis during the duration of the trial: HD >=2 times
per week or PD >=4 times per week including incremental schedule; subjects on
continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis
(APD) are eligible.

- Hemoglobin concentration as measured by HemoCue (range inclusive): 8 to 10.5 g/dL
(5-6.5 millimoles per liter [mmol/L]) at screening and 8-11.0 g/dL (5 to 6.8 mmol/L)
at randomization.

- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the consent form and in this protocol.
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Planned living-related or living-unrelated kidney transplant during the study.

- Ferritin: <=100 nanograms per milliliter (ng/mL) (<=100 micrograms per liter [mcg/L])
at screening or after IV iron supplementation.

- Transferrin saturation (TSAT): <=20% at screening or after IV iron supplementation.

- Vitamin B12 (cobalamin): Below the lower limit of the reference range at screening or
after vitamin B12 supplementation.

- Folate: <2.0 ng/mL (<4.5 nanomoles per liter [nmol/L]) at screening.

- Aplasias: History of bone marrow aplasia or pure red cell aplasia (PRCA).

- Other causes of anemia: Untreated pernicious anemia, thalassemia major, sickle cell
disease, or myelodysplastic syndrome.

- Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or
esophageal ulcer disease or clinically significant GI bleeding <=10 weeks prior to
screening through to randomization (Day 1).

- Use of any Erythropoiesis-stimulating agent (ESA) treatment within 8 weeks prior to
screening except for limited use as part of dialysis initiation. Note : Limited use is
defined as no more than 6 weeks of short acting ESA (rhEPO or biosimilars; maximum of
20000 unit total) or long acting ESA (darbepoetin alfa [maximum of 100 mcg total] or
methoxy polyethylene glycol-epoetin beta [maximum of 125 mcg total]) received before
or after starting dialysis.

- Myocardial infarction or acute coronary syndrome: <=10 weeks prior to screening
through to randomization (Day 1).

- Stroke or transient ischemic attack: <=10 weeks prior to screening through to
randomization (Day 1).

- Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA)
functional classification system.

- Current uncontrolled hypertension as determined by the Investigator that would
contraindicate the use of rhEPO.

- QT correction using Bazett's (QTcB) (Day 1): QTcB >500 milliseconds (msec), or QTcB
>530 msec in subjects with bundle branch block. There is no QTc exclusion for subjects
with a predominantly ventricular paced rhythm.

- Liver disease (any one of the following): 1. Alanine transaminase (ALT) >2 times upper
limit of normal (ULN) (screening only). 2. Bilirubin >1.5 times ULN (screening only)
(NOTE: Isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated
and direct bilirubin <35%). 3. Current unstable liver or biliary disease per
investigator assessment, generally defined by the presence of ascites, encephalopathy,
coagulopathy, hypoalbuminemia, 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.

- 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 (i.e.
Bosniak Category II F, III or IV) >3 centimeter (cm). The only exception is localized
squamous cell or basal cell carcinoma of the skin that has been definitively treated
>=10 weeks prior to screening.

- History of severe allergic or anaphylactic reactions or hypersensitivity to excipients
in the investigational product or to darbepoetin alfa.

- Use of strong Cytochrome P4502C8 (CYP2C8) inhibitors (example gemfibrozil) or strong
CYP2C8 inducers (example rifampin/rifampicin).

- Use of other investigational agent or device prior to screening through to
randomization (Day 1). At screening, this exclusion applies to use of the
investigational agent within 30 days or within five half-lives (whichever is longer).

- Any prior treatment with daprodustat for treatment duration of >30 days.

- Females only: Subject is pregnant [as confirmed by a positive serum human chorionic
gonadotropin (hCG) test for females of reproductive potential (FRP) only], subject is
breastfeeding, or subject is of reproductive potential and does not agree to follow
one of the contraceptive options in the List of Highly Effective Methods for Avoiding
Pregnancy.

- Any other condition, clinical or laboratory abnormality, or examination finding that
the investigator considers would put the subject at unacceptable risk, which may
affect study compliance (example intolerance to rhEPO) or prevent understanding of the
aims or investigational procedures or possible consequences of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Liverpool
Recruitment hospital [2] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [3] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [4] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [5] 0 0
GSK Investigational Site - St Albans
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3021 - St Albans
Recruitment outside Australia
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United States of America
State/province [1] 0 0
California
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United States of America
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Connecticut
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Florida
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Georgia
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Illinois
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Indiana
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Iowa
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Kentucky
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Puglia
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Volzhskiy
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Cape Town
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Puerto Real
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Sevilla
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Birmingham
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Doncaster
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London
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Middlesbrough

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this multi-center study is to evaluate the efficacy and safety of daprodustat
in subjects with anemia associated with CKD.
Trial website
https://clinicaltrials.gov/show/NCT03029208
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications