Phase 3
N=614
Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat in Non-Dialysis Subjects Evaluating Hemoglobin (Hgb) and Quality of Life (ASCEND-NHQ)
Anaemia
Bottom Line
View on ClinicalTrials.gov: NCT03409107 ↗Enrolled (actual)
614
Serious AEs
21.2%
Results posted
Nov 2021
Primary outcome: Primary: Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28) — 0.19; 1.58 Grams per deciliter — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Daprodustat (GSK1278863) (Drug); Placebo (Drug); Iron therapy (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Oct 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28) |
0.19; 1.58 | <0.0001 sig |
| SECONDARY Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period |
18; 77 | <0.0001 sig |
| SECONDARY Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28 |
1.93; 7.29 | 0.0005 sig |
| SECONDARY Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive) |
8; 52 | <0.0001 sig |
| SECONDARY Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Hodges-Lehmann Estimate) |
0.00; 53.59 | — |
| SECONDARY Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Mann-Whitney Estimate) |
0.00; 53.59 | <0.0001 sig |
| SECONDARY Change From Baseline in Post-randomization Hgb at Week 28 |
0.20; 1.56 | <0.0001 sig |
| SECONDARY Rate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria |
18.88; 1.33 | 0.0002 sig |
| SECONDARY Change From Baseline by Domain and Single Item Scores on the Chronic Kidney Disease -Anemia Questionnaire (CKD-AQ) Symptom Questionnaire |
2.81; 8.72; 0.62; 3.55; 0.48; 4.27 | <0.0001 sig |
| SECONDARY Change From Baseline in Patient Global Impression of Severity (PGI-S) |
-0.04; -0.18 | 0.0391 sig |
| SECONDARY Change From Baseline in the SF-36 Physical Functioning Domain |
1.23; 3.80 | 0.0858 |
| SECONDARY Change From Baseline of the SF-36 Individual Items in the Vitality Domain |
-0.02; 0.16; 0.09; 0.26; 0.16; 0.34 | 0.0357 sig |
| SECONDARY Number of Participants Currently Employed as Per Work Productivity and Activity Impairment Questionnaire: Anemic Symptoms Clinical Practice Version (WPAI-ANS-CPV) |
195; 204; 54; 46; 183; 212 | — |
| SECONDARY Change From Baseline in WPAI-ANS-CPV: Percent Time Missed From Work |
-2.4; -6.1; 0.9; 4.2; 0.0; 0.3 | — |
| SECONDARY Change From Baseline in WPAI-ANS-CPV: Mean Hours Missed From Work in the Past 7 Days |
0.1; -1.8; 1.4; 2.4; 0.3; 1.0 | — |
| SECONDARY Change From Baseline in WPAI: Percent Impairment at Work |
-5.1; -11.3; -4.6; -8.8; -9.6; -9.0 | — |
| SECONDARY Change From Baseline in WPAI: Percent Overall Work Impairment |
-4.3; -12.0; 0.5; -3.2; -9.3; -8.4 | — |
| SECONDARY Change From Baseline in WPAI: Percent Regular Daily Activity Impairment |
-4.6; -7.7; -5.2; -8.6; -6.7; -12.2 | — |
| SECONDARY Change From Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) Utility Score |
0.01; 0.03 | 0.1098 |
| SECONDARY Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score |
0.80; 5.30 | 0.0120 sig |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) at Week 28 |
-0.63; -0.23; -0.96; 0.84; -0.82; 0.49 | 0.6106 |
| SECONDARY Percentage of Participants With at Least One Blood Pressure (BP) Exacerbation Event |
26; 32 | 0.0680 |
Summary
The purpose of this multi-center study in non-dialysis participants with anemia associated with CKD is to evaluate safety, efficacy and quality of life of daprodustat compared to placebo.
Eligibility Criteria
Inclusion Criteria
- >=18 years of age at the time of signing the informed consent.
- Have CKD, confirmed at screening: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by Estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
- Participants with Stable HemoCue Hgb from 8.5 to 10.5 at screening visit (Week -4) and from 8.5 to 10.0 g/dL at randomization (Day 1).
- Participants may receive up to one intravenous (IV) iron dose within the 8 weeks prior to screening and NO IV iron use between screening visit and randomization (Day 1).
- If needed, participant may be on stable maintenance oral iron supplementation. There should be 30 days.
- MI or acute coronary syndrome within the 8 weeks prior to screening through to randomization. (Day 1).
- Stroke or transient ischemic attack within the 8 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.
- QT interval corrected by Bazett's formula (QTcB) >500 milliseconds (msec) or QTcB >530 msec in participants with bundle branch block. There is no corrected QT interval (QTc) exclusion for participants with a predominantly paced rhythm.
- Alanine transaminase (ALT) >2x upper limit of normal (ULN) at screening (Week -4).
- Bilirubin >1.5xULN at screening (Week -4).
- 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.
- 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 (for example, Bosniak Category II F, III or IV) > 3 centimeters (cm).
- Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
- Current uncontrolled hypertension as determined by the investigator.
Data sourced from ClinicalTrials.gov (NCT03409107). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.