Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat –Forearm Blood Flow (ASCEND-FBF)
- Conditions
- anemia associated with chronic kidney diseaseMedDRA version: 21.1Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Body processes [G] - Physiological processes [G07]
- Registration Number
- EUCTR2017-002268-42-GB
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 62
Age
1. Participant must be at least 18 years of age inclusive, at the time of signing the
informed consent.
Type of Participant and Disease Characteristics
2. Participants who are Stage 3, 4 or 5 CKD defined by eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula (Levey, 2009).
3. Hgb as measured by HemoCue at screening visit and Day 1 is = 11.0 g/dL (= 110 g/L).
4. Palpable brachial artery as assessed at screening.
5. Participants,if necessary, may be on stable maintenance oral iron supplementation supplementation(<50% change in overall dose and compliance of 80% of prescribed doses in the 4 weeks prior to and including the screening period). If participants have been on intravenous (IV) iron, then participants will not have received IV iron for 4 weeks prior to the Day 1 visit.
Sex
6. Male or female
a. Female participants:
A female participant is eligible to participate if she is not pregnant (see Appendix 5 of the study protocol), not breastfeeding, and at least one of the following conditions applies:
(i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 of the study protocol
OR
(ii) A WOCBP who has been on an approved form of contraceptive as defined in
Appendix 5 of the study protocol for the 4 weeks prior to Day 1 and agrees to follow the contraceptive guidance in Appendix 5 until the follow-up visit.
Informed Consent
7. Capable of giving signed informed consent as described in Appendix 3 of the study protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
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 62
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Medical Conditions
1. On dialysis or clinical evidence of impending need to initiate dialysis within 12
weeks of Day 1.
2. Planned kidney transplant within 12 weeks of Day 1.
3. Presence of an arteriovenous (AV) fistula.
Prior/Concomitant Therapy
4. rhEPO use within the 12 weeks prior to the screening visit and through Day 1.
5. History of severe allergic or anaphylactic reactions or hypersensitivity to the study treatment or challenge agents, or excipients in the study treatments or challenge agents (see daprodustat IB for list of excipients, and the Study Reference Manual (SRM) for product sheets for darbepoetin alfa and the challenge agents).
6. Planned use of any prescription or non-prescription drugs or dietary supplements that are prohibited from screening until all assessments on Day 42 have been successfully completed (see Section 7.7.2 of the study protocol).
Prior/Concurrent Clinical Study Experience
7. The participant has participated in a clinical trial and has received an experimental investigational product within the prior 30 days or within 5 half lives of the investigational product (whichever is longer) prior to screening and through Day 1.
Diagnostic assessments
8. At or below the lower limit of the reference range at screening for Vitamin B12 (may rescreen in a minimum of 8 weeks).
9. Ferritin = 50 ng/mL (= 50 µg/L) at screening.
10. Transferrin saturation (TSAT) = 15% (0.15) at screening.
11. Folate < 2.0 ng/mL (4.5 nmol/L; may rescreen in a minimum of 8 weeks) at
screening.
12. High sensitivity C-reactive protein (hs-CRP) = 50 µg/(= 50 mg/L) at screening.
Other Exclusions
13. Myocardial infarction or acute coronary syndrome = 12 weeks prior to screening and through Day 1.
14. Hospitalization for greater than 24 hours = 12 weeks prior to screening and through Day 1.
15. Stroke or transient ischemic attack = 12 weeks prior to screening and through Day 1.
16. Class IV heart failure, as defined by the New York Heart Association (NYHA)
functional classification system.
17. Resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 100 mmHg at screening visit or current uncontrolled hypertension as determined by the investigator.
18. QT interval corrected for heart rate using Bazett’s formula (QTcB): QTcB >500 msec, or QTcB >530 msec in participants with bundle branch block. There is
no QTc exclusion for participants with a predominantly ventricular paced rhythm.
19. Active chronic inflammatory disease that could impact erythropoiesis. A partial list can be found in the Study Reference Manual (SRM).
20. History of bone marrow aplasia or pure red cell aplasia.
21. Conditions, other than anemia of CKD, which can affect erythropoiesis. A partial list can be found in the SRM.
22. Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease OR
clinically significant GI bleeding from = 8 weeks prior to screening and through Day 1.
23. Liver disease (any of the following):
-Alanine transaminase (ALT) > 2x upper limit of normal (ULN; screening only)
-Bilirubin > 1.5x ULN (screening only)
NOTE: Isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated
and direct bilirubin < 35%
-Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic
gallstones).
24. Major surgery within the 12 weeks prior to screening and through Day 1, or planned during the study.
25. Anticipated or planned vascular access surge
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method