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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01906489
Recruitment Status : Completed
First Posted : July 24, 2013
Results First Posted : July 1, 2022
Last Update Posted : July 21, 2022
Sponsor:
Information provided by (Responsible Party):
Akebia Therapeutics

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.

Condition or disease Intervention/treatment Phase
Anemia Chronic Kidney Disease Drug: AKB-6548 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 210 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 23, 2013
Actual Primary Completion Date : September 3, 2014
Actual Study Completion Date : September 3, 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AKB-6548 Drug: AKB-6548
Oral dose administered once daily for 20 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.

Placebo Comparator: Placebo Drug: Placebo
Oral Placebo administered once daily for 20 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.




Primary Outcome Measures :
  1. Percentage of Participants Achieving a Successful Hemoglobin Response [ Time Frame: Weeks 19 and 20 ]
    Hemoglobin (Hgb) response was defined as participants with mean Hgb ≥11.0 grams per deciliter (g/dL) (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving Erythropoiesis-Stimulating Agents (ESA) or transfusion.


Secondary Outcome Measures :
  1. Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study [ Time Frame: Up to 20 Weeks ]
    Participants who have experienced an excursion in Hgb to ≥13.0 g/dL at any time during the study were considered as "failures". Data was presented for failures.

  2. Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value [ Time Frame: Weeks 19 and 20 ]
    Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing). Analysis of this secondary outcome measure is a reanalysis of the primary outcome measure whereby the response was determined solely by the Hgb value and receiving rescue therapy did not make the participant a failure.

  3. Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group [ Time Frame: Weeks 19 and 20 ]
    Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Treatment Naïve group, defined as participants who had never received treatment with an ESA and who had a screening Hgb level of ≤10.5 g/dL.

  4. Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group [ Time Frame: Weeks 19 and 20 ]
    Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Previously Treated group, defined as participants who had previously received ≥1 dose of an ESA, had been off of ESA therapy for ≥11 weeks at the time of screening, and had a screening Hgb level of ≤10.5 g/dL.

  5. Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group [ Time Frame: Weeks 19 and 20 ]
    Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Actively Treated group, defined as participants who had been actively treated with an ESA for a minimum of 4 months before screening, had received at least 2 doses within the last 4 months, had received their last dose within 6 weeks before screening, and had a screening Hgb level ≥9.5 g/dL and ≤12.0 g/dL.

  6. Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population [ Time Frame: Weeks 19 and 20 ]
    Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Analysis of this secondary outcome measure was performed in the mITT population.

  7. Change From Baseline in Hemoglobin [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 ]
    Blood samples were collected to assess Hgb. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hgb concentration increased.

  8. Absolute Values of Hemoglobin [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 ]
    Blood samples were collected at indicated time points for analysis of hemoglobin

  9. Change From Baseline in Hematocrit [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 ]
    Blood samples were collected to assess Hematocrit. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hematocrit concentration increased.

  10. Absolute Values of Hematocrit [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 ]
    Blood samples were collected at indicated time points for analysis of Hematocrit.

  11. Change From Baseline in Red Blood Cell Count [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 ]
    Blood samples were collected to assess red blood cell count. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated red blood cell count increased.

  12. Absolute Values of Red Blood Cell Count [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 ]
    Blood samples were collected at indicated time points for analysis of red blood cell count.

  13. Change From Baseline in Reticulocyte Count [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 ]
    Blood samples were collected to assess reticulocyte count. Baseline was defined as mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated reticulocyte count increased.

  14. Absolute Values of Reticulocyte Count [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 ]
    Blood samples were collected at indicated time points for analysis of reticulocyte count.

  15. Percentage of Participants Who Received ESA Rescue [ Time Frame: Up to 20 Weeks ]
    Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.

  16. Mean Number of ESA Rescue Doses Administered Per Participant [ Time Frame: Up to 20 Weeks ]
    Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.

  17. Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue [ Time Frame: Up to 20 Weeks ]
    Participants were administered packed red blood cell transfusion as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia

  18. Number of Packed Red Blood Cell Transfusion Administered Per Participant [ Time Frame: Up to 20 Weeks ]
    Participants were administered packed red blood cells as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.

  19. Time to First Transfusion or ESA Rescue Medication Intake [ Time Frame: Up to 20 Weeks ]
    Rescue therapy was defined as red blood cell transfusion or ESA administration in participants meeting Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.

  20. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: Up to 20 Weeks ]
    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.

  21. Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values [ Time Frame: Up to 20 Weeks ]
    Parameters assessed for laboratory values included hematology, serum chemistry, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant changes.

  22. Number of Participants With Clinically Significant Changes From Baseline in Vital Signs [ Time Frame: Up to 20 Weeks ]
    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.

  23. Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings [ Time Frame: Up to 20 Weeks ]
    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.

  24. Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings [ Time Frame: Up to 20 Weeks ]
    A Baseline physical examination was performed at screening. Otherwise, abbreviated physical examinations were conducted and were to include heart, lung, and abdomen. The investigator was responsible for reviewing laboratory results for clinically significant changes.


Other Outcome Measures:
  1. Exploratory: Change From Baseline in Iron and Total Iron Binding Capacity (TIBC) [ Time Frame: Baseline and up to Week 20 ]
  2. Exploratory: Change From Baseline in Transferrin [ Time Frame: Baseline and up to Week 20 ]
  3. Exploratory: Change From Baseline in Transferrin Saturation [ Time Frame: Baseline and up to Week 20 ]
  4. Exploratory: Mean Weekly Dose of Intravenous Elemental Iron Administered [ Time Frame: Baseline and up to Week 20 ]
  5. Exploratory: Absolute Values of Iron and Total Iron Binding Capacity (TIBC) [ Time Frame: Baseline and up to Week 20 ]
  6. Exploratory: Absolute Values of Transferrin [ Time Frame: Baseline and up to Week 20 ]
  7. Exploratory: Absolute Values of Transferrin Saturation [ Time Frame: Baseline and up to Week 20 ]
  8. Exploratory: Absolute Values of Reticulocyte Hemoglobin Content [ Time Frame: Baseline and up to Week 20 ]
  9. Exploratory: Change From Baseline in Reticulocyte Hemoglobin Content [ Time Frame: Baseline and up to Week 20 ]
  10. Exploratory: Change From Baseline in Hemoglobin A1c [ Time Frame: Baseline and up to Week 20 ]
  11. Exploratory: Absolute Values of Hemoglobin A1c [ Time Frame: Baseline and up to Week 20 ]
  12. Exploratory: Absolute Values of Lipids [ Time Frame: Baseline and up to Week 20 ]
  13. Exploratory: Change From Baseline in Lipids [ Time Frame: Baseline and up to Week 20 ]
  14. Exploratory: Change From Baseline in Hepcidin [ Time Frame: Baseline and up to Week 20 ]
  15. Exploratory: Absolute Values of Hepcidin [ Time Frame: Baseline and up to Week 20 ]
  16. Exploratory: Change From Baseline in Vascular Endothelial Growth Factor (VEGF) [ Time Frame: Baseline and up to Week 20 ]
  17. Exploratory: Absolute Values of Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin [ Time Frame: Baseline and up to Week 20 ]
  18. Exploratory: Change From Baseline in Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin [ Time Frame: Baseline and up to Week 20 ]
  19. Exploratory: Neurocognitive Functioning as a Measure [ Time Frame: Baseline and up to Week 20 ]
  20. Exploratory: Patient-Reported Outcome Measures [ Time Frame: Baseline and up to Week 20 ]
  21. Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites [ Time Frame: Baseline and up to Week 20 ]
  22. Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites [ Time Frame: Baseline ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 82 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01906489


Locations
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United States, Arizona
Glendale, Arizona, United States
Tucson, Arizona, United States
United States, California
Azusa, California, United States
Chula Vista, California, United States
Downey, California, United States
El Centro, California, United States
La Mesa, California, United States
Long Beach, California, United States
Riverside, California, United States
Sacramento, California, United States
San Diego, California, United States
United States, Colorado
Arvada, Colorado, United States
Westminster, Colorado, United States
United States, Florida
Lauderdale Lakes, Florida, United States
Port Charlotte, Florida, United States
Tampa, Florida, United States
United States, Georgia
Augusta, Georgia, United States
Macon, Georgia, United States
United States, Idaho
Meridian, Idaho, United States
United States, Illinois
Evergreen Park, Illinois, United States
United States, Louisiana
Lafayette, Louisiana, United States
Shreveport, Louisiana, United States
United States, Michigan
Detroit, Michigan, United States
Lansing, Michigan, United States
Petoskey, Michigan, United States
Pontiac, Michigan, United States
United States, Missouri
Farmington, Missouri, United States
Kansas City, Missouri, United States
United States, Nevada
Las Vegas, Nevada, United States
United States, New Mexico
Albuquerque, New Mexico, United States
United States, New York
Flushing, New York, United States
Mineola, New York, United States
New Rochelle, New York, United States
Rosedale, New York, United States
United States, North Carolina
Asheville, North Carolina, United States
Charlotte, North Carolina, United States
Rocky Mount, North Carolina, United States
Wilmington, North Carolina, United States
United States, Ohio
Cincinnati, Ohio, United States
United States, South Carolina
Columbia, South Carolina, United States
United States, Tennessee
Knoxville, Tennessee, United States
United States, Texas
Arlington, Texas, United States
Austin, Texas, United States
Edinburg, Texas, United States
Houston, Texas, United States
San Antonio, Texas, United States
United States, Utah
Saint George, Utah, United States
Sponsors and Collaborators
Akebia Therapeutics
Investigators
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Study Director: Chief Medical Officer Akebia Therapeutics Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Akebia Therapeutics
ClinicalTrials.gov Identifier: NCT01906489    
Other Study ID Numbers: AKB-6548-CI-0007
First Posted: July 24, 2013    Key Record Dates
Results First Posted: July 1, 2022
Last Update Posted: July 21, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Akebia Therapeutics:
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
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Anemia
Hematologic Diseases
Urologic Diseases
Renal Insufficiency