Back to resultsSafety and Efficacy Study for AKB-6548 in Participants With Chronic Kidney Disease and Anemia
Primary Purpose
Anemia, Kidney Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AKB-6548
Sponsored by
About this trial
This is an interventional treatment trial for Anemia focused on measuring anemia, chronic kidney disease, CKD, chronic renal insufficiency, renal impairment, erythropoietin, safety, efficacy, tolerability, pharmacokinetics
Eligibility Criteria
Key Inclusion Criteria:
- 18 to 79 years of age, inclusive
- Chronic Kidney Disease Stage 3 or Stage 4
- Hemoglobin (Hgb) < 10.5 g/dl
- TSAT > 20% and CBC indicating normocytic red blood cell morphology
Key Exclusion Criteria:
- BMI > 40
- 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 10 weeks prior to the Screening visit
- Participants meeting the criteria of ESA resistance within the previous 4 months
- Individual doses of intravenous iron of 250 mg or larger within the past 21 days
- AST or ALT >1.8x 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AKB-6548
Arm Description
Outcomes
Primary Outcome Measures
Mean Change From Baseline in Hemoglobin (Hgb) on Day 29
Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates that hemoglobin concentration increased.
Secondary Outcome Measures
Mean Change From Baseline in Hematocrit on Day 29
Blood samples were collected to assess hematocrit. A positive change from baseline indicates hematocrit concentration increased.
Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29
Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates RBC count increased.
Mean Change From Baseline in Absolute Reticulocyte Count on Day 29
Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline). A positive change from baseline indicates absolute reticulocyte count increased.
Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29
Blood samples were collected to assess reticulocyte Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates reticulocyte Hgb content increased.
Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29
Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).
Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29
Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).
Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29
Blood samples were collected to assess hematocrit.
Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29
Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).
Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29
Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline).
Change From Baseline in Ferritin on Day 29
Blood samples were collected to assess ferritin. A positive change from baseline indicates ferritin content increased.
Change From Baseline in Iron on Day 29
Blood samples were collected to assess iron. A positive change from baseline indicates iron content increased.
Change From Baseline in Total Iron Binding Capacity on Day 29
Blood samples were collected to assess total iron binding capacity. A positive change from baseline indicates total iron binding capacity increased.
Change From Baseline in Transferrin Saturation on Day 29
Blood samples were collected to assess transferrin saturation. The transferrin saturation is the ratio of the serum iron concentration and the total iron-binding capacity, expressed as a percentage. A positive change from baseline indicates transferrin saturation increased.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An Adverse Event (AE) was defined as any untoward medical occurrence, signs, symptoms, disease, or laboratory or physiological observations occurring in a participant administered with drug, regardless of a causal relationship with that treatment or usage. This also included all suspected adverse medication reactions, reactions from medication overdose, abuse, withdrawal, sensitivity, toxicity, unrelated illnesses, including worsening a pre-existing condition, injury, or accidents. Serious Adverse Events (SAEs) was defined as any life-threatening condition; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or death.
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Parameters assessed for laboratory values included hematology, chemistry, urinalysis, and coagulation. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values
Parameters assessed for vital signs included sitting (at rest for a minimum of 5 minutes) heart rate, respiratory rate, body temperature, and blood pressure. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The investigator was responsible for reviewing laboratory results for clinical significance.
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The parameters evaluated from the participant ECG trace included PR interval, QT interval, QRS interval, and QTc (corrected).
Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29
Serum samples were collected from the participants at the defined time points. Trough concentration was defined as the concentration of drug in the blood immediately before the next dose is administered. Trough concentration was calculated using the validated liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01235936
Brief Title
Safety and Efficacy Study for AKB-6548 in Participants With Chronic Kidney Disease and Anemia
Official Title
Phase 2a Open-Label Pilot Study to Assess the Pharmacodynamic Response, Pharmacokinetics, Safety, and Tolerability of 28-Day Repeat Oral Doses of AKB-6548 in Subjects With Anemia Secondary to Chronic Kidney Disease (CKD), Stages 3 and/or 4
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
October 21, 2010 (undefined)
Primary Completion Date
April 13, 2011 (Actual)
Study Completion Date
May 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akebia Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, pharmacodynamics and pharmacokinetics of repeat doses of orally administered AKB-6548 in pre-dialysis participants with anemia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Kidney Disease
Keywords
anemia, chronic kidney disease, CKD, chronic renal insufficiency, renal impairment, erythropoietin, safety, efficacy, tolerability, pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AKB-6548
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AKB-6548
Intervention Description
Different dose levels
Primary Outcome Measure Information:
Title
Mean Change From Baseline in Hemoglobin (Hgb) on Day 29
Description
Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates that hemoglobin concentration increased.
Time Frame
Baseline; Day 29
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Hematocrit on Day 29
Description
Blood samples were collected to assess hematocrit. A positive change from baseline indicates hematocrit concentration increased.
Time Frame
Baseline; Day 29
Title
Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29
Description
Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates RBC count increased.
Time Frame
Baseline; Day 29
Title
Mean Change From Baseline in Absolute Reticulocyte Count on Day 29
Description
Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline). A positive change from baseline indicates absolute reticulocyte count increased.
Time Frame
Baseline; Day 29
Title
Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29
Description
Blood samples were collected to assess reticulocyte Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates reticulocyte Hgb content increased.
Time Frame
Baseline; Day 29
Title
Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29
Description
Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).
Time Frame
Day 29
Title
Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29
Description
Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).
Time Frame
Day 29
Title
Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29
Description
Blood samples were collected to assess hematocrit.
Time Frame
Day 29
Title
Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29
Description
Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).
Time Frame
Day 29
Title
Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29
Description
Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline).
Time Frame
Day 29
Title
Change From Baseline in Ferritin on Day 29
Description
Blood samples were collected to assess ferritin. A positive change from baseline indicates ferritin content increased.
Time Frame
Baseline; Day 29
Title
Change From Baseline in Iron on Day 29
Description
Blood samples were collected to assess iron. A positive change from baseline indicates iron content increased.
Time Frame
Baseline; Day 29
Title
Change From Baseline in Total Iron Binding Capacity on Day 29
Description
Blood samples were collected to assess total iron binding capacity. A positive change from baseline indicates total iron binding capacity increased.
Time Frame
Baseline; Day 29
Title
Change From Baseline in Transferrin Saturation on Day 29
Description
Blood samples were collected to assess transferrin saturation. The transferrin saturation is the ratio of the serum iron concentration and the total iron-binding capacity, expressed as a percentage. A positive change from baseline indicates transferrin saturation increased.
Time Frame
Baseline; Day 29
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
An Adverse Event (AE) was defined as any untoward medical occurrence, signs, symptoms, disease, or laboratory or physiological observations occurring in a participant administered with drug, regardless of a causal relationship with that treatment or usage. This also included all suspected adverse medication reactions, reactions from medication overdose, abuse, withdrawal, sensitivity, toxicity, unrelated illnesses, including worsening a pre-existing condition, injury, or accidents. Serious Adverse Events (SAEs) was defined as any life-threatening condition; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or death.
Time Frame
Up to 2 weeks post 28 days of treatment
Title
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Description
Parameters assessed for laboratory values included hematology, chemistry, urinalysis, and coagulation. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time Frame
Up to 2 weeks post 28 days of treatment
Title
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values
Description
Parameters assessed for vital signs included sitting (at rest for a minimum of 5 minutes) heart rate, respiratory rate, body temperature, and blood pressure. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time Frame
Up to 2 weeks post 28 days of treatment
Title
Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings
Description
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The investigator was responsible for reviewing laboratory results for clinical significance.
Time Frame
Up to 2 weeks post 28 days of treatment
Title
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Description
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The parameters evaluated from the participant ECG trace included PR interval, QT interval, QRS interval, and QTc (corrected).
Time Frame
Up to 2 weeks post 28 days of treatment
Title
Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29
Description
Serum samples were collected from the participants at the defined time points. Trough concentration was defined as the concentration of drug in the blood immediately before the next dose is administered. Trough concentration was calculated using the validated liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
Time Frame
Pre-dose at Day 8, 15, 22 and 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
18 to 79 years of age, inclusive
Chronic Kidney Disease Stage 3 or Stage 4
Hemoglobin (Hgb) < 10.5 g/dl
TSAT > 20% and CBC indicating normocytic red blood cell morphology
Key Exclusion Criteria:
BMI > 40
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 10 weeks prior to the Screening visit
Participants meeting the criteria of ESA resistance within the previous 4 months
Individual doses of intravenous iron of 250 mg or larger within the past 21 days
AST or ALT >1.8x 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chief Medical Officer
Organizational Affiliation
Akebia Therapeutics Inc.
Official's Role
Study Director
Facility Information:
City
Augusta
State/Province
Georgia
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Efficacy Study for AKB-6548 in Participants With Chronic Kidney Disease and Anemia
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