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

Anemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01906489
• Other study ID #: AKB-6548-CI-0007
• Status: Completed
• Phase: Phase 2
• Start date: July 23, 2013
• Est. completion date: September 3, 2014

Study information

• Verified date: June 2022
• Source: Akebia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: September 3, 2014
• Est. primary completion date: September 3, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 82 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• AKB-6548
Oral dose administered once daily for 20 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
• Placebo
Oral Placebo administered once daily for 20 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Akebia Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory: Change From Baseline in Iron and Total Iron Binding Capacity (TIBC)		Baseline and up to Week 20
Other	Exploratory: Change From Baseline in Transferrin		Baseline and up to Week 20
Other	Exploratory: Change From Baseline in Transferrin Saturation		Baseline and up to Week 20
Other	Exploratory: Mean Weekly Dose of Intravenous Elemental Iron Administered		Baseline and up to Week 20
Other	Exploratory: Absolute Values of Iron and Total Iron Binding Capacity (TIBC)		Baseline and up to Week 20
Other	Exploratory: Absolute Values of Transferrin		Baseline and up to Week 20
Other	Exploratory: Absolute Values of Transferrin Saturation		Baseline and up to Week 20
Other	Exploratory: Absolute Values of Reticulocyte Hemoglobin Content		Baseline and up to Week 20
Other	Exploratory: Change From Baseline in Reticulocyte Hemoglobin Content		Baseline and up to Week 20
Other	Exploratory: Change From Baseline in Hemoglobin A1c		Baseline and up to Week 20
Other	Exploratory: Absolute Values of Hemoglobin A1c		Baseline and up to Week 20
Other	Exploratory: Absolute Values of Lipids		Baseline and up to Week 20
Other	Exploratory: Change From Baseline in Lipids		Baseline and up to Week 20
Other	Exploratory: Change From Baseline in Hepcidin		Baseline and up to Week 20
Other	Exploratory: Absolute Values of Hepcidin		Baseline and up to Week 20
Other	Exploratory: Change From Baseline in Vascular Endothelial Growth Factor (VEGF)		Baseline and up to Week 20
Other	Exploratory: Absolute Values of Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin		Baseline and up to Week 20
Other	Exploratory: Change From Baseline in Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin		Baseline and up to Week 20
Other	Exploratory: Neurocognitive Functioning as a Measure		Baseline and up to Week 20
Other	Exploratory: Patient-Reported Outcome Measures		Baseline and up to Week 20
Other	Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites		Baseline and up to Week 20
Other	Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites		Baseline
Primary	Percentage of Participants Achieving a Successful Hemoglobin Response	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.	Weeks 19 and 20
Secondary	Percentage of Participants With Hemoglobin Value =13.0 g/dL at Any Time During the Study	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.	Up to 20 Weeks
Secondary	Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value	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.	Weeks 19 and 20
Secondary	Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group	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.	Weeks 19 and 20
Secondary	Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group	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.	Weeks 19 and 20
Secondary	Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group	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.	Weeks 19 and 20
Secondary	Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population	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.	Weeks 19 and 20
Secondary	Change From Baseline in Hemoglobin	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.	Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Secondary	Absolute Values of Hemoglobin	Blood samples were collected at indicated time points for analysis of hemoglobin	Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Secondary	Change From Baseline in Hematocrit	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.	Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Secondary	Absolute Values of Hematocrit	Blood samples were collected at indicated time points for analysis of Hematocrit.	Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Secondary	Change From Baseline in Red Blood Cell Count	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.	Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Secondary	Absolute Values of Red Blood Cell Count	Blood samples were collected at indicated time points for analysis of red blood cell count.	Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Secondary	Change From Baseline in Reticulocyte Count	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.	Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Secondary	Absolute Values of Reticulocyte Count	Blood samples were collected at indicated time points for analysis of reticulocyte count.	Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Secondary	Percentage of Participants Who Received ESA Rescue	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.	Up to 20 Weeks
Secondary	Mean Number of ESA Rescue Doses Administered Per Participant	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.	Up to 20 Weeks
Secondary	Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue	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	Up to 20 Weeks
Secondary	Number of Packed Red Blood Cell Transfusion Administered Per Participant	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.	Up to 20 Weeks
Secondary	Time to First Transfusion or ESA Rescue Medication Intake	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.	Up to 20 Weeks
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)	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.	Up to 20 Weeks
Secondary	Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values	Parameters assessed for laboratory values included hematology, serum chemistry, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant changes.	Up to 20 Weeks
Secondary	Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	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.	Up to 20 Weeks
Secondary	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.	Up to 20 Weeks
Secondary	Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings	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.	Up to 20 Weeks