Clinical trial NCT01381094: 42-Day Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia
Official title: Phase 2a Randomized, Double-Blind, Placebo-Controlled, Dose Range Study to Assess the Pharmacodynamic Response, Pharmacokinetics, Safety, and Tolerability of 42-Day Repeat Oral Doses of AKB-6548 in Subjects With Anemia Secondary to Chronic Kidney Disease (CKD), Stages 3 and 4
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Kidney Disease
Keywords: anemia
chronic kidney disease
CKD
chronic renal insufficiency
renal impairment
erythropoietin
safety
efficacy
tolerability
pharmacokinetics
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 \<60 mL/min), not yet on dialysis
* Hemoglobin (Hgb) ≤ 10.5 g/dL
* Transferring saturation ≥ 20%
* Ferritin ≥ 50 ng/mL

Key Exclusion Criteria:

* Body mass index \>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

Primary outcomes:
measure: Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)
timeFrame: Baseline, Week 6
Secondary outcomes:
measure: Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
timeFrame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
measure: Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
timeFrame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
measure: 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)
timeFrame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
measure: Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
timeFrame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
measure: Change From Baseline in Reticulocyte Hgb Content at Week 6
timeFrame: Baseline, Week 6
measure: Maximum Change From Baseline in Hgb
timeFrame: Baseline; up to Week 8
measure: Maximum Change From Baseline in HCT
timeFrame: Baseline; up to Week 8
measure: Maximum Change From Baseline in RBC Count
timeFrame: Baseline; up to Week 8
measure: Maximum Change in Absolute Reticulocyte Count From Baseline
timeFrame: Baseline; up to Week 8
measure: 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
timeFrame: Up to Week 6 (End of the Dosing Period)
measure: Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period
timeFrame: Up to Week 6 (End of The Dosing Period)
measure: Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period
timeFrame: Up to Week 6 (End of The Dosing Period)
measure: Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period
timeFrame: Up to Week 6 (End of The Dosing Period)
measure: Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period
timeFrame: Up to Week 6 (End of The Dosing Period)
measure: Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
timeFrame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
measure: Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
timeFrame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
measure: Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
timeFrame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
measure: Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
timeFrame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
measure: Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
timeFrame: Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8)
measure: Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8)
timeFrame: Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8)
measure: Change From Baseline in Hepcidin at Week 6
timeFrame: Baseline, Week 6
measure: Mean Plasma Vadadustat Concentrations on Week 2 and Week 4
timeFrame: Week 2: Pre-dose and post-dose; Week 4: Pre-dose
measure: Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4
timeFrame: Week 2: Pre-dose; Week 4: Pre-dose
measure: Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter
timeFrame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
measure: Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings
timeFrame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
measure: Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
timeFrame: Baseline, Week 6
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
timeFrame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
Other outcomes:
Locations:
city: Pine Bluff
country: United States
state: Arkansas
city: Covina
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Lynwood
country: United States
state: California
city: Riverside
country: United States
state: California
city: San Dimas
country: United States
state: California
city: Whittier
country: United States
state: California
city: Coral Springs
country: United States
state: Florida
city: Lauderdale Lakes
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Wichita
country: United States
state: Kansas
city: Shreveport
country: United States
state: Louisiana
city: Springfield
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Pontiac
country: United States
state: Michigan
city: Warren
country: United States
state: Michigan
city: Bethpage
country: United States
state: New York
city: Mineola
country: United States
state: New York
city: Wilmington
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Knoxville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Akebia Therapeutics Inc.
name: Chief Medical Officer
role: STUDY_DIRECTOR
References:
citation: Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
citation: Martin ER, Smith MT, Maroni BJ, Zuraw QC, deGoma EM. Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease. Am J Nephrol. 2017;45(5):380-388. doi: 10.1159/000464476. Epub 2017 Mar 25.