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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02876835




Registration number
NCT02876835
Ethics application status
Date submitted
19/08/2016
Date registered
24/08/2016

Titles & IDs
Public title
Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Non-Dialysis (ASCEND-ND)
Scientific title
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
Secondary ID [1] 0 0
2016-000542-65
Secondary ID [2] 0 0
200808
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 - Placebo
Treatment: Drugs - Iron Therapy

Experimental: Daprodustat - Participants will receive oral daprodustat once daily.

Active comparator: Darbepoetin alfa - Participants will be administered darbepoetin alfa subcutaneously (SC).


Treatment: Drugs: Daprodustat
The initial dose or oral daprodustat for ESA naïve subjects is based on Hgb and for ESA users is based on prior ESA dose. The dose is adjusted thereafter in order to achieve the target range.

Treatment: Drugs: Darbepoetin alfa
The initial dose of darbepoetin alfa to be administered for SC injection for ESA naïve subjects is based in Hgb and weight, and for ESA users is based on converting the prior ESA dose to the nearest available study darbepoetin alfa dose. The dose is adjusted thereafter in order to achieve the target range. IV darbepoetin alfa can be considered for participants transitioning to hemodialysis.

Treatment: Drugs: Placebo
Oral placebo tablets will be taken from Week -4 up to randomization (Day 1).

Treatment: Drugs: Iron Therapy
Participants will receive supplemental iron therapy if ferritin is \<=100 ng/mL or TSAT is \<=20%. The investigator will choose the route of administration and dose of iron.

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

Outcomes
Primary outcome [1] 0 0
Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period (Non-inferiority Analysis)
Timepoint [1] 0 0
Up to 4.3 person-years for CV follow-up time period
Primary outcome [2] 0 0
Mean Change From Baseline in Hgb Levels Over the Evaluation Period (Week 28 to Week 52)
Timepoint [2] 0 0
Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Secondary outcome [1] 0 0
Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period (Superiority Analysis)
Timepoint [1] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [2] 0 0
Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period
Timepoint [2] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [3] 0 0
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period
Timepoint [3] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [4] 0 0
Time to First Occurrence of Chronic Kidney Disease (CKD) Progression During CV Events Follow-up Time Period
Timepoint [4] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [5] 0 0
Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period
Timepoint [5] 0 0
Up to 4.3 person-years for vital status follow-up time period
Secondary outcome [6] 0 0
Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period
Timepoint [6] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [7] 0 0
Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Timepoint [7] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [8] 0 0
Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Timepoint [8] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [9] 0 0
Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis)
Timepoint [9] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [10] 0 0
Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period
Timepoint [10] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [11] 0 0
Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period
Timepoint [11] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [12] 0 0
Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period
Timepoint [12] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [13] 0 0
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period
Timepoint [13] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [14] 0 0
Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period
Timepoint [14] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [15] 0 0
Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period
Timepoint [15] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [16] 0 0
Time to First Occurrence of Confirmed 40% Decline in eGFR During CV Events Follow-up Time Period
Timepoint [16] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [17] 0 0
Time to First Occurrence of Chronic Dialysis During CV Events Follow-up Time Period
Timepoint [17] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [18] 0 0
Time to First Occurrence of Kidney Transplant During CV Events Follow-up Time Period
Timepoint [18] 0 0
Up to 4.3 person-years for CV follow-up time period
Secondary outcome [19] 0 0
Change From Baseline in Post-randomization Hgb Levels at Week 52
Timepoint [19] 0 0
Baseline (Pre-dose on Day 1) and Week 52
Secondary outcome [20] 0 0
Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)
Timepoint [20] 0 0
Week 28 to Week 52
Secondary outcome [21] 0 0
Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis
Timepoint [21] 0 0
Week 28 to Week 52
Secondary outcome [22] 0 0
Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis
Timepoint [22] 0 0
Week 28 to Week 52
Secondary outcome [23] 0 0
Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis
Timepoint [23] 0 0
Week 28 to end of study (4.3 person-years for follow-up time period)
Secondary outcome [24] 0 0
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis
Timepoint [24] 0 0
Week 28 to end of study (4.3 person-years for follow-up time period)
Secondary outcome [25] 0 0
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52
Timepoint [25] 0 0
Baseline (Week -4) and Week 52
Secondary outcome [26] 0 0
Change From Baseline in SBP, DBP, MAP at End of Treatment
Timepoint [26] 0 0
Baseline (Week -4) and 51.1 months
Secondary outcome [27] 0 0
Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years
Timepoint [27] 0 0
Day 1 to end of treatment (51.1 months)
Secondary outcome [28] 0 0
Number of Participants With at Least One BP Exacerbation Event During Study
Timepoint [28] 0 0
Day 1 to end of treatment (51.1 months)
Secondary outcome [29] 0 0
Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria
Timepoint [29] 0 0
Day 1 to 51.1 months
Secondary outcome [30] 0 0
Change From Baseline in On-treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52
Timepoint [30] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [31] 0 0
Change From Baseline in On-treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Timepoint [31] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [32] 0 0
Change From Baseline in On-treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52
Timepoint [32] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [33] 0 0
Change From Baseline in On-treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Timepoint [33] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [34] 0 0
Change From Baseline in On-treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Timepoint [34] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [35] 0 0
Change From Baseline in On-treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52
Timepoint [35] 0 0
Baseline (Pre-dose on Day 1) and Week 52
Secondary outcome [36] 0 0
Change From Baseline in On-treatment EQ Visual Analogue Scale (EQ-VAS) at Week 52
Timepoint [36] 0 0
Baseline (Pre-dose on Day 1) and Week 52
Secondary outcome [37] 0 0
Change From Baseline in On-treatment Chronic Kidney Disease- Anemia Symptoms Questionnaire (CKD-AQ) at Weeks 8, 12, 28, 52
Timepoint [37] 0 0
Baseline (Day 1) and Weeks 8, 12, 28, 52
Secondary outcome [38] 0 0
Change From Baseline in On-treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52
Timepoint [38] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [39] 0 0
Change From Baseline in Post-randomization Estimated Glomerular Filtration Rate (eGFR) at Week 52
Timepoint [39] 0 0
Baseline (Pre-dose on Day 1) and Week 52

Eligibility
Key inclusion criteria
* Age: 18 to 99 years of age (inclusive)
* CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by electronic eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula.
* Erythropoietin-stimulating agents (ESAs)/Hgb: 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 for the 6 weeks prior to screening and continuing between screening and randomization.
* For Group 1 (not using ESAs), Hgb concentration at Week -8 and Week 1 should be 8 to 10 gram per deciliter (g/dL). For Group 2 (ESA users), Hgb concentration at Week -8 should be 8 to 12 g/dL and at Week 1 should be 8 to 11 g/dL.
* >=80% and <=120% compliance with placebo during run-in period.
* Informed consent (screening only): capable of giving signed informed consent which includes compliance with the requirements and restrictions.
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 90 days after study start (Day 1).
* Kidney transplant: Planned living-related or living-unrelated kidney transplant within 52 weeks after study start (Day 1).
* Ferritin: <=100 nanograms (ng)/milliliter (mL) (<=100 micrograms/liter [L]) at screening.
* Transferrin saturation (TSAT) (screening only): <=20%.
* Aplasias: History of bone marrow aplasia or pure red cell aplasia.
* 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 <=4 weeks prior to screening through to randomization (Day 1).
* MI or acute coronary syndrome: <=4 weeks prior to screening through to randomization (Day 1).
* Stroke or transient ischemic attack: <=4 weeks prior to screening through to randomization (Day 1).
* Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart Association (NYHA) functional classification system.
* Current uncontrolled hypertension: Current uncontrolled hypertension as determined by the investigator.
* Bazett's corrected QT interval (QTcB) (Day 1): QTcB >500 millisecond (msec), or QTcB >530 msec in subjects with bundle branch block. There is no Q-T Interval Corrected for Heart Rate (QTc) exclusion for subjects with a predominantly ventricular paced rhythm.
* Alanine transaminase (ALT): >2x upper limit of normal (ULN) at screening.
* Bilirubin: >1.5xULN at screening.
* 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.
* 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 (example [e.g.] Bosniak Category II F, III or IV) > 3 centimeter (cm); with the exception of localized squamous cell or basal cell carcinoma of the skin that has been definitively treated >=4 weeks prior to screening.
* Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product, or darbepoetin alfa.
* Drugs and supplements: Use of strong inhibitors of Cytochrome P4502C8 (CYP2C8) (e.g., gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin).
* Other study participation: 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).
* Prior treatment with daprodustat: Any prior treatment with daprodustat for treatment duration of >30 days.
* Females only: Subject is pregnant [as confirmed by a positive urine human chorionic gonadotrophin (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.
* Other Conditions: 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 (e.g., intolerance to darbepoetin alfa) 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
Completed
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)
ACT,NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Garran
Recruitment hospital [2] 0 0
GSK Investigational Site - Concord
Recruitment hospital [3] 0 0
GSK Investigational Site - Gosford
Recruitment hospital [4] 0 0
GSK Investigational Site - Kingswood
Recruitment hospital [5] 0 0
GSK Investigational Site - Kogarah
Recruitment hospital [6] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [7] 0 0
GSK Investigational Site - St Leonards
Recruitment hospital [8] 0 0
GSK Investigational Site - Wollongong
Recruitment hospital [9] 0 0
GSK Investigational Site - Nambour
Recruitment hospital [10] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [11] 0 0
GSK Investigational Site - Reservoir
Recruitment hospital [12] 0 0
GSK Investigational Site - St Albans
Recruitment hospital [13] 0 0
GSK Investigational Site - Nedlands
Recruitment hospital [14] 0 0
GSK Investigational Site - Liverpool
Recruitment postcode(s) [1] 0 0
2606 - Garran
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2250 - Gosford
Recruitment postcode(s) [4] 0 0
2747 - Kingswood
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
2031 - Randwick
Recruitment postcode(s) [7] 0 0
2065 - St Leonards
Recruitment postcode(s) [8] 0 0
2500 - Wollongong
Recruitment postcode(s) [9] 0 0
4560 - Nambour
Recruitment postcode(s) [10] 0 0
3004 - Melbourne
Recruitment postcode(s) [11] 0 0
3073 - Reservoir
Recruitment postcode(s) [12] 0 0
3021 - St Albans
Recruitment postcode(s) [13] 0 0
6009 - Nedlands
Recruitment postcode(s) [14] 0 0
2107 - Liverpool
Recruitment outside Australia
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Beroun
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State/province [95] 0 0
Aalborg
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Germany
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Germany
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Germany
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India
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Poland
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Lodz
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Poland
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Szczecin
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Poland
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Portugal
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Portugal
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Portugal
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Ho Chi Minh

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Available to whom?
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.gsk.com/en-gb/innovation/trials/data-transparency


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.