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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03409107

Registration number

NCT03409107

Ethics application status

Date submitted

8/01/2018

Date registered

24/01/2018

Titles & IDs

Public title

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)

Scientific title

A 28-week, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-center, Study in Recombinant Human Erythropoietin (rhEPO) naïve Non-dialysis Participants With Anemia Associated With Chronic Kidney Disease to Evaluate the Efficacy, Safety and Effects on Quality of Life of Daprodustat Compared to Placebo

Secondary ID [1]

2017-002270-39

Secondary ID [2]

205270

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Anaemia

Condition category

Condition code

Renal and Urogenital

Kidney disease

Renal and Urogenital

Other renal and urogenital disorders

Blood

Anaemia

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Daprodustat (GSK1278863)
Treatment: Drugs - Placebo
Treatment: Drugs - Iron therapy

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

Placebo comparator: Placebo receivers - Participants will receive oral placebo once daily

Treatment: Drugs: Daprodustat (GSK1278863)
Daprodustat will be available as 9 millimeter (mm) or 7 mm film-coated tablets. Daprodustat will be administered once daily via oral route and can be taken without regard to food.

Treatment: Drugs: Placebo
Daprodustat matching placebo will be available as 9 mm or 7 mm film coated tablets. Placebo will be administered once daily via oral route and can be taken without regard to food.

Treatment: Drugs: Iron therapy
Iron therapy will be administered if ferritin is \<50 Nano gram per milliliter and/or TSAT is \<15 percent.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28)

Assessment method [1]

Blood samples were collected at given time points from participants for hemoglobin measurements. Evaluation period hemoglobin value was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 24 to Week 28 inclusive). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of Covariance (ANCOVA) model with terms for treatment, Baseline hemoglobin, and region.

Timepoint [1]

Baseline (Day 1) and Week 24 to Week 28

Secondary outcome [1]

Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period

Assessment method [1]

Blood samples were collected at given time points for hemoglobin measurements. Evaluation period hemoglobin value was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 24 to Week 28 inclusive). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Percentage of participants with hemoglobin increase of \>=1.0 grams per deciliter from Baseline to evaluation period was analyzed using Cochran-Mantel-Haenszel (CMH) chi-squared test. The percentage values presented has been rounded off.

Timepoint [1]

Baseline (Day 1) and Week 24 to Week 28

Secondary outcome [2]

Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28

Assessment method [2]

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the 8 health domains: Physical Functioning, Role-Physical (role limitations caused by physical problems), Social Functioning, Bodily Pain, Mental Health, Role-Emotional (role limitations caused by emotional problems), Vitality, and General Perception of Health.Each domain is scored from 0 (poorer health) to 100 (better health). Vitality domain score ranges from 0-100; higher score indicates a better health state \& better functioning. Change from Baseline was calculated as Post-Dose Visit Value at Week 28 minus Baseline. For primary analysis, the missing on-treatment Week 28 SF-36 Vitality domain scores were imputed using pre-specified multiple imputations. Baseline value was latest non-missing pre-dose assessment on or before randomization date. Analysis was performed using ANCOVA model with terms for treatment, Baseline score, and region.

Timepoint [2]

Baseline (Day 1) and Week 28

Secondary outcome [3]

Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive)

Assessment method [3]

Mean hemoglobin during the evaluation period was defined as the mean of all evaluable hemoglobin values during the evaluation period (Week 24 to Week 28 inclusive) including any evaluable unscheduled hemoglobin values that were taken during this period. Percentage of participants with Hgb response was defined as participants with mean Hgb within range (11-12 grams per deciliter during the evaluation period (Week 24 to Week 28 inclusive) and it was analyzed using Cochran-Mantel-Haenszel (CMH) chi-squared test. The percentage values presented has been rounded off.

Timepoint [3]

Week 24 to Week 28

Secondary outcome [4]

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)

Assessment method [4]

Percentage of days for which participant's Hgb was within the target range of 11-12 grams per deciliter during the evaluation period (Week 24 to Week 28 inclusive), including any unscheduled evaluable Hgb values that were taken during this time period. Percentage of time for which Hgb was within the target range (11-12 grams per deciliter) for a participant was calculated by dividing 'the total number of days that Hgb was within range during Week 24 to 28' by 'the total number of days the participant remained on treatment during Week 24 to 28'.

Timepoint [4]

Week 24 to Week 28

Secondary outcome [5]

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)

Assessment method [5]

Timepoint [5]

Week 24 to Week 28

Secondary outcome [6]

Change From Baseline in Post-randomization Hgb at Week 28

Assessment method [6]

Blood samples were collected at given time points for hemoglobin measurements. Change from Baseline in Hgb was analyzed using a mixed model repeated measures (MMRM) approach. Change from Baseline was calculated as Post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Timepoint [6]

Baseline (Day 1) and Week 28

Secondary outcome [7]

Rate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

Assessment method [7]

The incidence rate of participants permanently stopping randomized treatment due to meeting rescue criteria is presented.

Timepoint [7]

Up to Week 28

Secondary outcome [8]

Change From Baseline by Domain and Single Item Scores on the Chronic Kidney Disease -Anemia Questionnaire (CKD-AQ) Symptom Questionnaire

Assessment method [8]

CKD-AQ is 21-item patient reported outcomes measure assessing symptoms \& symptom impact in participants with anemia associated with CKD.CKD-AQ identified 3 domains:1.Tired/Low Energy/Weak scale consisting of ten items;2.Chest Pain/Shortness of Breath scale consisting of four items and 3.Cognitive scale consisting of three items;Single items included: 4.Difficulty Sleeping;5.Difficulty Standing for long periods of time;6.Severity-Shortness of breath while sitting/resting;7.Time with Shortness of breath while not doing activity.Single-item measures were recorded based on 0-100 scoring with 0 is worst possible \& 100 is best possible score.Total domain score is calculated as average of items in each domain \& ranged from 0-100 where 0 is worst possible and 100 is best possible score.Change from Baseline was calculated as post-dose visit value minus Baseline.Baseline was latest non-missing pre-dose assessment on or before randomization date. Adjusted mean \& standard error is presented.

Timepoint [8]

Baseline (Day 1) and Week 28

Secondary outcome [9]

Change From Baseline in Patient Global Impression of Severity (PGI-S)

Assessment method [9]

The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated worse outcome. Change from Baseline was calculated as Post-Dose visit value minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Adjusted mean and standard error is presented.

Timepoint [9]

Baseline (Day 1) and Week 28

Secondary outcome [10]

Change From Baseline in the SF-36 Physical Functioning Domain

Assessment method [10]

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following eight health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality, and general perception of health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning domain score ranges from 0-100; higher score indicates a better health state and better functioning. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Timepoint [10]

Baseline (Day 1) and Week 28

Secondary outcome [11]

Change From Baseline of the SF-36 Individual Items in the Vitality Domain

Assessment method [11]

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following eight health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality, and general perception of health. Individual vitality items include: 1. Did you feel full of life?, 2. Did you have a lot of energy?, 3. Did you feel worn out?, 4. Did you feel tired?. Score of each item in the vitality domain ranges from 0-100; higher score indicates better health state and better functioning. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Timepoint [11]

Baseline (Day 1) and Week 28

Secondary outcome [12]

Number of Participants Currently Employed as Per Work Productivity and Activity Impairment Questionnaire: Anemic Symptoms Clinical Practice Version (WPAI-ANS-CPV)

Assessment method [12]

WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism(time missed from work), presenteeism(impairment at work) and regular daily activity impairment. WPAI questions (Q) were:1) currently employed,2) work time missed due to problem, 3) impairment while working due to problem, 4) overall work impairment due to problem, 5) activity impairment due to problem. WPAI generates 4 domain scores:percent (%) of work time missed(absenteeism),% of impairment while working(presenteeism),% of overall work impairment(absenteeism and presenteeism combined),% of activity impairment. Number of participants currently employed as per WPAI-ANS-CPV is presented.

Timepoint [12]

Week 8, Week 12 and Week 28

Secondary outcome [13]

Change From Baseline in WPAI-ANS-CPV: Percent Time Missed From Work

Assessment method [13]

WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism (time missed from work), presenteeism (impairment at work) and regular daily activity impairment. WPAI questions (Q) were: 1) currently employed, 2) work time missed due to problem, 3) impairment while working due to problem, 4)overall work impairment due to problem, 5) activity impairment due to problem. Percent work time missed due to problem was a subscale and calculated as: Q2/(Q2+Q4) for those who were currently employed. Subscale score was expressed as an impairment percentage (range: 0-100%) where higher numbers indicate greater impairment and less productivity. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Timepoint [13]