Anemia Studies in CKD: Erythropoiesis via a Novel PHIDaprodustat- in Incident Dialysis

Phase 1

Active, not recruiting

• Conditions: Therapeutic area: Body processes [G] - Physiological processes [G07]; Anemia associated with chronic kidney disease; MedDRA version: 19.0Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disorders

• Registration Number: EUCTR2016-000507-86-ES
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01-03
• Study Completion: 2020-09-24
• Last Update Posted: 2022-04-19

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 312

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply at screening and randomization (Day 1) unless otherwise specified.
1. Age (confirm at screening): 18 to 99 years of age inclusive
2. Dialysis: Planning to start chronic dialysis within the next 4 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 = 2X/week, or
- Daily PD (Including continuous and automated PD)
3. Hemoglobin concentration as measured by HemoCue (range inclusive): 8-10.5 g/dL (5-6.5 mmol/L) at screening and 8-11.0 g/dL (5-6.8 mmol/L) at randomization
4. Informed consent: capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol
Note: The country-specific requirements for France ONLY for the informed consent process is provided in Appendix 11 (see Section 12.11.1, Item 3 for details)
5. Other study eligibility criteria considerations: The country-specific requirements for France ONLY for the eligibility for inclusion in this study is provided in Appendix 11 (see Section 12.11.1, Item 1 for details)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 210
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

A subject will not be eligible for participation in this study if any of the following criteria apply at screening or at randomization (Day 1), unless otherwise specified.
CKD-related criteria
1. Kidney transplant: Planned living-related donor kidney transplant during the study.
Anemia related criteria
2. Ferritin: =100 ng/mL (=100 µg/L) at screening or after IV iron supplementation.
3. TSAT: =20% at screening or after IV iron supplementation.
4. Vitamin B12: Below the lower limit of the reference range at screening or after vitamin B12 supplementation
5. Folate: <2.0 ng/mL (<4.5 nmol/ L) at screening
6. Aplasias: History of bone marrow aplasia or pure red cell aplasia (PRCA).
7. Other causes of anemia: Pernicious anemia, thalassemia major, sickle cell disease, or myelodysplastic syndrome.
8. 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).
Erythropoiesis treatment criteria
9. Use of any ESA treatment within 8 weeks prior to screening except for limited use as part of dialysis initiation. Limited use is defined as no more than 6 weeks of short acting ESA (rhEPO or biosimilars; maximum of 20000 U total) or long acting ESA (darbepoetin alfa [maximum of 100 µg total] or methoxy polyethylene glycol-epoetin beta [maximum of 125 µg total]) received before or after starting dialysis.
Cardiovascular disease-related criteria
10. Myocardial infarction or acute coronary syndrome: =10 weeks prior to screening through to randomization (Day 1).
11. Stroke or transient ischemic attack: =10 weeks prior to screening through to randomization (Day 1).
12. Heart failure: Chronic Class IV heart failure, as defined by the New York HeartAssociation (NYHA) functional classification system.
13. Current uncontrolled hypertension: Current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of rhEPO.
14. 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 paced rhythm
Other disease-related criteria
15. 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 subjectotherwise meets entry criteria.
16. 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 (i.e. Bosniak Category II F, III or IV) > 3cm. The only exception is localized squamous cell or basal cell carcinoma of the skin that has been definitively treated =10 weeks prior to screening. Concomitant medications and other study treatment-related criteria
17. Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product (refer to daprodustat IB) or to da

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare daprodustat to rhEPO for Hgb efficacy (non-inferiority);Secondary Objective: To compare daprodustat to rhEPO on the use of intravenous (IV) iron;Primary end point(s): Mean change in Hgb between baseline and evaluation period (EP, mean over Weeks 28-52);Timepoint(s) of evaluation of this end point: Between week 28 and week 52

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Average monthly IV iron dose (mg)/subject from baseline to Week 52;Timepoint(s) of evaluation of this end point: Between baseline and Week 52