Trial Outcomes & Findings for Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis Subjects (NCT NCT04707768)

Last Updated: 2025-01-15

Results Overview

The Baseline Hb was defined as the average of last 2 central laboratory Hb measurements of samples taken at or prior to the first dose. The average for the PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as PEP value minus the Baseline value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

456 participants

Primary outcome timeframe

Baseline; Weeks 20 to 26

Results posted on

2025-01-15

Participant Flow

This was a randomzied, open-label, active-controlled study of the efficacy and safety of conversion from long-acting Erythropoiesis-stimulating Agent (ESA) (Methoxy polyethylene glycol-epoetin beta \[Mircera®\]) to vadadustat Three Times Weekly (TIW) for the maintenance treatment of anemia in hemodialysis participants.

A total of 456 participants were enrolled in the study. Participants were randomized 1:1:1 to Vadadustat 600 milligrams (mg) TIW Vadadustat 900 mg TIW or to remain on Mircera® according to the dialysis center's protocol.

Participant milestones

Participant milestones
Measure	Vadadustat 600 mg TIW Participants were randomized to receive Vadadustat at an initial oral dose of 600 mg TIW. Up-and-down titration was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb level	Vadadustat 900 mg TIW Participants were randomized to receive Vadadustat at an initial oral dose of 900 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Mircera® Participants were randomized to Mircera® were already on Mircera®, the initial dosing regimen in the study was based on the prior dosing regimen
Overall Study STARTED	152	152	152
Overall Study COMPLETED	99	98	118
Overall Study NOT COMPLETED	53	54	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Vadadustat 600 mg TIW Participants were randomized to receive Vadadustat at an initial oral dose of 600 mg TIW. Up-and-down titration was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb level	Vadadustat 900 mg TIW Participants were randomized to receive Vadadustat at an initial oral dose of 900 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Mircera® Participants were randomized to Mircera® were already on Mircera®, the initial dosing regimen in the study was based on the prior dosing regimen
Overall Study Adverse Event	9	18	3
Overall Study Investigator's Discretion	8	4	3
Overall Study Withdrawal by Subject	6	8	2
Overall Study Lack of Efficacy	1	3	0
Overall Study Lost to Follow-up	0	0	3
Overall Study Death	13	11	13
Overall Study Protocol Violation	2	1	0
Overall Study Non Compliance with Study Drug	1	0	0
Overall Study Transplant	4	4	8
Overall Study Other	9	5	2

Baseline Characteristics

Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vadadustat 600 mg TIW n=152 Participants Participants were randomized to receive Vadadustat at an initial oral dose of 600 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Vadadustat 900 mg TIW n=152 Participants Participants were randomized to receive Vadadustat at an initial oral dose of 900 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Mircera® n=152 Participants Participants were randomized to Mircera® were already on Mircera®, the initial dosing regimen in the study was based on the prior dosing regimen	Total n=456 Participants Total of all reporting groups
Age, Continuous	59.4 Years STANDARD_DEVIATION 14.20 • n=5 Participants	61.9 Years STANDARD_DEVIATION 13.27 • n=7 Participants	61.6 Years STANDARD_DEVIATION 12.80 • n=5 Participants	61.0 Years STANDARD_DEVIATION 13.45 • n=4 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	60 Participants n=7 Participants	66 Participants n=5 Participants	194 Participants n=4 Participants
Sex: Female, Male Male	84 Participants n=5 Participants	92 Participants n=7 Participants	86 Participants n=5 Participants	262 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	42 Participants n=5 Participants	40 Participants n=7 Participants	56 Participants n=5 Participants	138 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	110 Participants n=5 Participants	109 Participants n=7 Participants	95 Participants n=5 Participants	314 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	56 Participants n=5 Participants	59 Participants n=7 Participants	53 Participants n=5 Participants	168 Participants n=4 Participants
Race (NIH/OMB) White	86 Participants n=5 Participants	87 Participants n=7 Participants	92 Participants n=5 Participants	265 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline; Weeks 20 to 26

Population: Randomized Population

Outcome measures

Outcome measures
Measure	Vadadustat 600 mg TIW n=152 Participants Participants were randomized to receive Vadadustat at an initial oral dose of 600 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Vadadustat 900 mg TIW n=152 Participants Participants were randomized to receive Vadadustat at an initial oral dose of 900 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Mircera® n=152 Participants Participants were randomized to Mircera® were already on Mircera®, the initial dosing regimen in the study was based on the prior dosing regimen
Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)	-0.07 Grams per deciliter (g/dL) Standard Error 0.095	0.14 Grams per deciliter (g/dL) Standard Error 0.095	0.36 Grams per deciliter (g/dL) Standard Error 0.092

SECONDARY outcome

Timeframe: Baseline; Weeks 46 to 52

Population: Randomized population.

The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the SEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 46 through 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as SEP value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Vadadustat 600 mg TIW n=152 Participants Participants were randomized to receive Vadadustat at an initial oral dose of 600 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Vadadustat 900 mg TIW n=152 Participants Participants were randomized to receive Vadadustat at an initial oral dose of 900 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Mircera® n=152 Participants Participants were randomized to Mircera® were already on Mircera®, the initial dosing regimen in the study was based on the prior dosing regimen
Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)	-0.11 Grams per deciliter Standard Error 0.110	-0.22 Grams per deciliter Standard Error 0.123	0.16 Grams per deciliter Standard Error 0.102

Adverse Events

Vadadustat 600 mg TIW

Serious events: 68 serious events

Other events: 61 other events

Deaths: 14 deaths

Vadadustat 900 mg TIW

Serious events: 66 serious events

Other events: 67 other events

Deaths: 12 deaths

Mircera®

Serious events: 67 serious events

Other events: 64 other events

Deaths: 17 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Vadadustat 600 mg TIW n=151 participants at risk Participants were randomized to receive Vadadustat at an initial oral dose of 600 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Vadadustat 900 mg TIW n=150 participants at risk Participants were randomized to receive Vadadustat at an initial oral dose of 900 mg TIW. Up-and-down titration was allowed during the study based on Hb level measurements to maintain target Hb level	Mircera® n=150 participants at risk Participants were randomized to Mircera® were already on Mircera®, the initial dosing regimen in the study was based on the prior dosing regimen
Infections and infestations COVID 19	12.6% 19/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	12.0% 18/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	12.7% 19/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Gastrointestinal disorders Diarrhoea	10.6% 16/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	14.0% 21/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	7.3% 11/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Gastrointestinal disorders Nausea	7.9% 12/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	8.7% 13/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	4.7% 7/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Metabolism and nutrition disorders Hyperkalaemia	4.0% 6/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	8.7% 13/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	8.0% 12/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Injury, poisoning and procedural complications Fall	7.3% 11/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	5.3% 8/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	7.3% 11/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Injury, poisoning and procedural complications Arteriovenous fistula site complication	4.6% 7/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	5.3% 8/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	4.7% 7/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.0% 9/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	5.3% 8/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	2.7% 4/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Vascular disorders Hypertension	3.3% 5/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	2.7% 4/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	7.3% 11/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Musculoskeletal and connective tissue disorders Back pain	5.3% 8/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	3.3% 5/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	3.3% 5/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Nervous system disorders Headache	2.0% 3/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	6.7% 10/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	3.3% 5/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication
Gastrointestinal disorders Vomiting	2.6% 4/151 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	3.3% 5/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication	5.3% 8/150 • Day 1 through Week 56 Safety Population included all participants who received at least 1 dose of study medication

Additional Information

Akebia Therapeutics, Inc.

Phone: 6178446128

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER