Phase 2 N=91 Randomized Quadruple-blind Treatment

42-Day Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia

Anemia · Kidney Disease

Bottom Line

View on ClinicalTrials.gov: NCT01381094 ↗

Enrolled (actual)

Serious AEs

8.8%

Results posted

Jul 2022

Primary outcome: Primary: Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) — 9.46; 9.93; 9.86; 9.67 Grams per deciliter (g/dL) — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: AKB-6548 (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Akebia Therapeutics
Primary completion: Feb 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)	9.46; 9.93; 9.86; 9.67; 9.83; 0.77	<0.0001 sig
SECONDARY Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	9.46; 9.93; 9.86; 9.67; 9.83; 0.06	=0.9355
SECONDARY Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	29.0; 29.6; 30.4; 29.6; 29.8; 0.5	=0.5219
SECONDARY Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	3.21; 3.38; 3.37; 3.25; 3.34; -0.01	=0.3943
SECONDARY Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	0.0766; 0.0569; 0.0811; 0.0674; 0.0700; 0.0022	=1.0000
SECONDARY Change From Baseline in Reticulocyte Hgb Content at Week 6	31.02; 31.44; 30.26; 31.54; 30.73; 0.37	=0.2065
SECONDARY Maximum Change From Baseline in Hgb	9.46; 9.93; 9.86; 9.67; 9.83; 1.04	<0.0001 sig
SECONDARY Maximum Change From Baseline in HCT	29.0; 29.6; 30.4; 29.6; 29.8; 2.94	=0.0002 sig
SECONDARY Maximum Change From Baseline in RBC Count	3.21; 3.38; 3.37; 3.25; 3.34; 0.31	<0.0001 sig
SECONDARY Maximum Change in Absolute Reticulocyte Count From Baseline	0.0766; 0.0569; 0.0811; 0.0674; 0.0700; 0.013	=0.0027 sig
SECONDARY Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period	3; 2; 2; 1; 2; 3	—
SECONDARY Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period	4; 3; 1; 1; 2; 4	—
SECONDARY Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period	4; 3; 2; 0; 1; 1	—
SECONDARY Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period	4; 3; 2; 3; 1; 2	—
SECONDARY Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period	1; 1; 4; 2; 3; 1	—
SECONDARY Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	66.0; 77.8; 76.1; 60.7; 67.6; -1.8	=0.6051
SECONDARY Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	153.4; 168.0; 173.1; 171.2; 175.5; 10.9	=0.0448 sig
SECONDARY Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	30.4; 32.4; 31.4; 26.5; 27.7; -1.5	=0.3953
SECONDARY Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	219.4; 245.8; 249.2; 231.8; 243.1; 9.2	=0.0294 sig
SECONDARY Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	349.5; 245.8; 332.3; 240.2; 200.8; -66.0	<0.0001 sig
SECONDARY Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8)	18.011; 4.339; 7.287; 8.826; 6.963; -3.538	—
SECONDARY Change From Baseline in Hepcidin at Week 6	326.35; 241.03; 242.51; 282.75; 258.29; -28.64	=0.5456
SECONDARY Mean Plasma Vadadustat Concentrations on Week 2 and Week 4	4358.28; 6640.04; 10791.79; 12443.17; 17036.82; 21371.63	—
SECONDARY Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4	1848.4; 2708.5; 5900.1; 6425.0; 1999.3; 2687.5	—
SECONDARY Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	9; 6; 8; 11; 11; 2	—
SECONDARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter	0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings	0; 0; 0; 0; 0	—
SECONDARY Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval	156.7; 174.6; 172.8; 187.8; 175.8; -0.8	—
SECONDARY Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values	0; 0; 0; 0; 0	—

Summary

The purpose of this study is to evaluate the dose response (efficacy), pharmacodynamic response, pharmacokinetics, safety, and tolerability of orally administered AKB-6548 in pre-dialysis participants with anemia with repeat dosing for 42 days.

Eligibility Criteria

Key Inclusion Criteria

18 to 79 years of age, inclusive
Chronic Kidney Disease (eGFR 42
Red blood cell transfusion within 12 weeks
Androgen therapy within the previous 21 days prior to study dosing
Therapy with any approved or experimental erythropoiesis stimulating agent (ESA) within the 11 weeks prior to the Screening visit
Participants meeting the criteria of ESA resistance within the previous 4 months
Individual doses of intravenous iron of greater than 250 mg within the past 21 days
Aspartate aminotransferase or alanine aminotransferase >1.8x upper limit of normal (ULN)
Alkaline phosphatase >2x ULN
Total bilirubin >1.5x ULN
Uncontrolled hypertension
New York Heart Association Class III or IV congestive heart failure
Myocardial infarction, acute coronary syndrome, or stroke within 6 months prior to dosing

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Data sourced from ClinicalTrials.gov (NCT01381094). 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.