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

Phase 2

Completed

• Conditions: Chronic Kidney Disease; Anemia
• Interventions: Drug: AKB-6548; Drug: Placebo

• Registration Number: NCT01906489
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-07-20
• Study First Submitted QC: 2013-07-20
• Study Start: 2013-07-23
• Study First Posted: 2013-07-24
• Primary Completion: 2014-09-03
• Study Completion: 2014-09-03
• Disposition First Submitted: 2014-11-12
• Disposition First Submitted QC: 2014-11-12
• Disposition First Posted: 2014-11-24
• Results First Submitted: 2022-04-22
• Status Verified: 2022-06
• Results First Submitted QC: 2022-06-07
• Results First Posted: 2022-07-01
• Last Update Submitted: 2022-07-12
• Last Update Posted: 2022-07-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 210

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AKB-6548	AKB-6548	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving a Successful Hemoglobin Response	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

Name	Time	Method
Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value	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.
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group	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.
Absolute Values of Hemoglobin	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
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group	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.
Absolute Values of Hematocrit	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.
Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study	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.
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group	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.
Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population	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.
Time to First Transfusion or ESA Rescue Medication Intake	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.
Change From Baseline in Red Blood Cell Count	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.
Number of Packed Red Blood Cell Transfusion Administered Per Participant	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.
Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings	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.
Change From Baseline in Hematocrit	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.
Absolute Values of Red Blood Cell Count	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.
Absolute Values of Reticulocyte Count	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.
Percentage of Participants Who Received ESA Rescue	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.
Mean Number of ESA Rescue Doses Administered Per Participant	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)	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.
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values	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.
Change From Baseline in Hemoglobin	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.
Change From Baseline in Reticulocyte Count	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.
Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue	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
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	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.
Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings	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.