Clinical trial NCT01906489: 20-Week Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia
Official title: Phase 2b Randomized, Double-Blind, Placebo-Controlled Study to Assess the Pharmacodynamic Response, Safety, and Tolerability to 20 Weeks of Oral Dosing of AKB-6548 in Participants With Anemia Secondary to Chronic Kidney Disease (CKD), GFR Categories G3a-G5 (Stages 3, 4, AND 5) (Pre-Dialysis)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Chronic Kidney Disease
Keywords: anemia
chronic kidney disease
CKD
chronic renal insufficiency
renal impairment
erythropoietin
kidney
oral anemia treatment
hemoglobin
hypoxia-inducible factor
HIF
hypoxia-inducible factor prolyl-hydroxylase inhibitor
HIF-PHI
efficacy
safety
pharmacokinetics
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2013-07-24
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 82
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 hemoglobin response (efficacy), safety, and tolerability of orally administered AKB-6548 in participants with Chronic Kidney Disease (pre-dialysis) with anemia with dosing for 20 weeks.


Eligibility criteria: Key Inclusion Criteria:

* 18 to 82 years of age, inclusive
* Chronic Kidney Disease with a GFR category of G3a-G5 and not yet on dialysis
* eGFR ≥ 10 and ≤ 65 mL/minute/1.73 m2
* Anemia secondary to CKD with an ESA status and a Screening HGB as per protocol
* Iron replete with ferritin and TSAT levels as defined per protocol

Key Exclusion Criteria:

* BMI \> 44.0 kg/m2
* Red blood cell transfusion within 11 weeks prior to the Screening visit
* Androgen therapy within the previous 21 days prior to the Screening visit
* Intravenous iron within the past 4 weeks prior to the Screening visit
* AST or ALT \>1.8x ULN, alkaline phosphatase \>2x ULN, or total bilirubin \>1.5x ULN
* Screening ECG with QTc \> 500 msec
* Uncontrolled hypertension
* Class III or IV congestive heart failure
* Myocardial infarction, acute coronary syndrome, or stroke within 6 months prior to the Screening visit

Primary outcomes:
measure: Percentage of Participants Achieving a Successful Hemoglobin Response
timeFrame: Weeks 19 and 20
Secondary outcomes:
measure: Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study
timeFrame: Up to 20 Weeks
measure: Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value
timeFrame: Weeks 19 and 20
measure: Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group
timeFrame: Weeks 19 and 20
measure: Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group
timeFrame: Weeks 19 and 20
measure: Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group
timeFrame: Weeks 19 and 20
measure: Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population
timeFrame: Weeks 19 and 20
measure: Change From Baseline in Hemoglobin
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
measure: Absolute Values of Hemoglobin
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
measure: Change From Baseline in Hematocrit
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
measure: Absolute Values of Hematocrit
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
measure: Change From Baseline in Red Blood Cell Count
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
measure: Absolute Values of Red Blood Cell Count
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
measure: Change From Baseline in Reticulocyte Count
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
measure: Absolute Values of Reticulocyte Count
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
measure: Percentage of Participants Who Received ESA Rescue
timeFrame: Up to 20 Weeks
measure: Mean Number of ESA Rescue Doses Administered Per Participant
timeFrame: Up to 20 Weeks
measure: Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue
timeFrame: Up to 20 Weeks
measure: Number of Packed Red Blood Cell Transfusion Administered Per Participant
timeFrame: Up to 20 Weeks
measure: Time to First Transfusion or ESA Rescue Medication Intake
timeFrame: Up to 20 Weeks
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Up to 20 Weeks
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
timeFrame: Up to 20 Weeks
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
timeFrame: Up to 20 Weeks
measure: Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings
timeFrame: Up to 20 Weeks
measure: Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings
timeFrame: Up to 20 Weeks
Other outcomes:
measure: Exploratory: Change From Baseline in Iron and Total Iron Binding Capacity (TIBC)
timeFrame: Baseline and up to Week 20
measure: Exploratory: Change From Baseline in Transferrin
timeFrame: Baseline and up to Week 20
measure: Exploratory: Change From Baseline in Transferrin Saturation
timeFrame: Baseline and up to Week 20
measure: Exploratory: Mean Weekly Dose of Intravenous Elemental Iron Administered
timeFrame: Baseline and up to Week 20
measure: Exploratory: Absolute Values of Iron and Total Iron Binding Capacity (TIBC)
timeFrame: Baseline and up to Week 20
measure: Exploratory: Absolute Values of Transferrin
timeFrame: Baseline and up to Week 20
measure: Exploratory: Absolute Values of Transferrin Saturation
timeFrame: Baseline and up to Week 20
measure: Exploratory: Absolute Values of Reticulocyte Hemoglobin Content
timeFrame: Baseline and up to Week 20
measure: Exploratory: Change From Baseline in Reticulocyte Hemoglobin Content
timeFrame: Baseline and up to Week 20
measure: Exploratory: Change From Baseline in Hemoglobin A1c
timeFrame: Baseline and up to Week 20
measure: Exploratory: Absolute Values of Hemoglobin A1c
timeFrame: Baseline and up to Week 20
measure: Exploratory: Absolute Values of Lipids
timeFrame: Baseline and up to Week 20
measure: Exploratory: Change From Baseline in Lipids
timeFrame: Baseline and up to Week 20
measure: Exploratory: Change From Baseline in Hepcidin
timeFrame: Baseline and up to Week 20
measure: Exploratory: Absolute Values of Hepcidin
timeFrame: Baseline and up to Week 20
measure: Exploratory: Change From Baseline in Vascular Endothelial Growth Factor (VEGF)
timeFrame: Baseline and up to Week 20
measure: Exploratory: Absolute Values of Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin
timeFrame: Baseline and up to Week 20
measure: Exploratory: Change From Baseline in Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin
timeFrame: Baseline and up to Week 20
measure: Exploratory: Neurocognitive Functioning as a Measure
timeFrame: Baseline and up to Week 20
measure: Exploratory: Patient-Reported Outcome Measures
timeFrame: Baseline and up to Week 20
measure: Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites
timeFrame: Baseline and up to Week 20
measure: Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites
timeFrame: Baseline
Locations:
city: Glendale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Azusa
country: United States
state: California
city: Chula Vista
country: United States
state: California
city: Downey
country: United States
state: California
city: El Centro
country: United States
state: California
city: La Mesa
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Riverside
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Arvada
country: United States
state: Colorado
city: Westminster
country: United States
state: Colorado
city: Lauderdale Lakes
country: United States
state: Florida
city: Port Charlotte
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Meridian
country: United States
state: Idaho
city: Evergreen Park
country: United States
state: Illinois
city: Lafayette
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Detroit
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Petoskey
country: United States
state: Michigan
city: Pontiac
country: United States
state: Michigan
city: Farmington
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Albuquerque
country: United States
state: New Mexico
city: Flushing
country: United States
state: New York
city: Mineola
country: United States
state: New York
city: New Rochelle
country: United States
state: New York
city: Rosedale
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Rocky Mount
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Columbia
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Edinburg
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Saint George
country: United States
state: Utah
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: Pergola PE, Spinowitz BS, Hartman CS, Maroni BJ, Haase VH. Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Kidney Int. 2016 Nov;90(5):1115-1122. doi: 10.1016/j.kint.2016.07.019. Epub 2016 Sep 17.