AnemiaPhase 2NCT02260193
16-Week Repeat Oral Dose Study of AKB-6548 for Anemia in Participants With End Stage Renal Disease (ESRD) Requiring Chronic Hemodialysis
A Phase 2 study testing AKB-6548 in people with Anemia and End Stage Renal Disease, run by Akebia Therapeutics at 16 sites in United States.
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 end stage renal disease undergoing chronic hemodialysis. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Anemia, End Stage Renal Disease
- What is being tested?
- AKB-6548
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 16 sitesUnited States
- Study dates
- 10 Sep 2014to 22 Jul 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 to 79 years inclusive
- Chronic Kidney Disease (CKD) Stage 5 on chronic hemodialysis for at least 3 months
- Anemia secondary to CKD treated with erythropoiesis stimulating agent and intravenous iron
Who cannot join
- Body mass index >44.0 kilograms per meter squared (kg/m^2)
- Transfusion within 8 weeks prior to Screening
- Alanine transaminase or total bilirubin >1.25x ULN
- Uncontrolled hypertension
- Class III or IV congestive heart failure
- Myocardial infarction, acute coronary syndrome, stroke or transient ischemic attack within 6 months prior to Screening
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Study site
Arlington, Texas
Study site
Arvada, Colorado
Study site
Astoria, New York
Study site
Augusta, Georgia
Study site
El Granada, California
Study site
Grand Prairie, Texas
Study site
Greenville, Texas
Study site
Houston, Texas
Study site
Long Beach, California
Study site
Mechanicsville, Virginia
Study site
Naples, Florida
Study site
North Miami Beach, Florida
Study site
San Dimas, California
Study site
Santa Clarita, California
Study site
Westminster, Colorado
Study site
Whittier, California
About this study
Official title: Phase 2 Open-Label Study to Assess the Efficacy, Safety, and Tolerability of AKB-6548 in Subjects With Anemia Secondary to End Stage Renal Disease (ESRD), Undergoing Chronic Hemodialysis.
The purpose of this study is to evaluate the hemoglobin response (efficacy), safety, and tolerability of orally administered AKB-6548 in participants with end stage renal disease undergoing chronic hemodialysis.
- Conditions
- Anemia, End Stage Renal Disease
- Being tested
- AKB-6548
- Keywords
- anemia, end stage renal disease, chronic kidney disease, CKD, dialysis, chronic renal insufficiency, renal impairment, erythropoietin, kidney, oral anemia treatment, hemoglobin, hypoxia-inducible factor, HIF, hypoxia-inducible factor propyl-hydroxylase inhibitor, HIF-PHI, pharmacokinetics
- Medical subject headings
- Anemia, Kidney Failure, Chronic, Renal Insufficiency, Chronic, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AKB-6548Drug
Starting dose 1. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
AKB-6548Drug
Starting dose 2. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
AKB-6548Drug
Starting dose 3. Oral dose administered three times weekly for 16 weeks. Dose adjustment based on hemoglobin levels as defined in the protocol.
| Study group | Role | What they receive |
|---|---|---|
| AKB-6548, starting dose 1 | Experimental | Not described Receives: Drug: AKB-6548 |
| AKB-6548, starting dose 2 | Experimental | Not described Receives: Drug: AKB-6548 |
| AKB-6548, starting dose 3 | Experimental | Not described Receives: Drug: AKB-6548 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average
Change from pre-dose average was calculated by the mid-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits.
Measured: Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8
Change From Pre-dose Average in Hgb Level to The End-of-study Average
Change from pre-dose average was calculated by the end-of-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
Measured: Pre-dose, Week 15, and Week 16
Change From Mid-study Average in Hgb Level to The End-of-study Average
Change from mid-study average was calculated by the end-of-study average minus the mid-study average. The mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
Measured: Week 7, Week 8, Week 15, and Week 16
Secondary outcomes (20)
Change From Baseline in Hgb
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the three samples obtained prior to dosing.
Measured: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Hematocrit
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hematocrit was defined as the last observation before the first dose of study medication.
Measured: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Red Blood Cell (RBC) Count
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC Count was defined as the average of the three samples obtained prior to dosing.
Measured: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Absolute Reticulocyte Count
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline absolute reticulocyte count was defined as the last observation before the first dose of study medication.
Measured: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Percent Reticulocyte Count
Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline percent reticulocyte count was defined as the last observation before the first dose of study medication.
Measured: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Reticulocyte Hgb Content
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline reticulocyte Hgb content was defined as the average of the three samples obtained prior to dosing.
Measured: Baseline, Week 2, Week 4, Week 8, and Week 16
Change From Baseline in Ferritin
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the last observation before the first dose of study medication.
Measured: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Hepcidin
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline hepcidin was defined as the last observation before the first dose of study medication.
Measured: Baseline, Week 8, and Week 16
Change From Baseline in Total Iron-Binding Capacity (TIBC)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the last observation before the first dose of study medication.
Measured: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Transferrin Saturation (TSAT)
Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline TSAT was defined as the last observation before the first dose of study medication.
Measured: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Iron
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron was defined as the last observation before the first dose of study medication.
Measured: Baseline, Week 4, Week 8, Week 12, and Week 16
Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy
ESA rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.
Measured: Up to Week 16
Number of Participants Who Received Blood Transfusion Rescue Therapy
Blood transfusion rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.
Measured: Up to Week 16
Mean Plasma Concentrations of Vadadustat
Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.
Measured: Pre-dialysis and post-dialysis on Week 2 and Week 16
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite
Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.
Measured: Pre-dialysis and post-dialysis on Week 2 and Week 16
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite
Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.
Measured: Pre-dialysis and post-dialysis on Week 2 and Week 16
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. A TEAE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. A SAE included AEs that met one or more of the following criteria/outcomes: death, lifethreatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect.
Measured: Up to Week 20
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Parameters assessed for vital signs included sitting blood pressure, pulse, respiratory rate, and body temperature. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Measured: Up to Week 20
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Parameters assessed for laboratory values included hematology, serum chemistry, urinalysis, iron indices, C-reactive protein, lipid profile, biomarkers, and pregnancy tests. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Measured: Up to Week 20
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings
A standard 12-lead ECG was performed following dosing in a supine position for approximately 5 minutes. ECGs were taken prior to vital sign assessments, circulatory access cannulation, and blood draws when possible. Clinical significance was determined by the investigator.
Measured: Up to Week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2014 (estimated)
- Study start10 Sep 2014
- Primary completion22 Jul 2015
- Study completion22 Jul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akebia Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, Akebia Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02260193
- Sponsor's protocol ID
- AKB-6548-CI-0011
- Status last verified
- Jun 2022
- First submitted
- 25 Sep 2014
- Last updated
- 1 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Open-Label Study to Assess the Efficacy, Safety, and Tolerability of AKB-6548 in Subjects With Anemia Secondary to End Stage Renal Disease (ESRD), Undergoing Chronic Hemodialysis.
- ClinicalTrials.gov ID
- NCT02260193
- Acronym / sponsor ID
- AKB-6548-CI-0011
- Conditions
- Anemia, End Stage Renal Disease
- Keywords
- anemia, end stage renal disease, chronic kidney disease, CKD, dialysis, chronic renal insufficiency, renal impairment, erythropoietin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Akebia TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 10 Sep 2014 (actual)
- Primary completion
- 22 Jul 2015 (actual)
- Study completion
- 22 Jul 2015 (actual)
- First posted
- 9 Oct 2014 (estimated)
- Results
- Posted 1 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the hemoglobin response (efficacy), safety, and tolerability of orally administered AKB-6548 in participants with end stage renal disease undergoing chronic hemodialysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AKB-6548, starting dose 1 | Experimental | Drug: AKB-6548 |
| AKB-6548, starting dose 2 | Experimental | Drug: AKB-6548 |
| AKB-6548, starting dose 3 | Experimental | Drug: AKB-6548 |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 18 to 79 years inclusive
- Chronic Kidney Disease (CKD) Stage 5 on chronic hemodialysis for at least 3 months
- Anemia secondary to CKD treated with erythropoiesis stimulating agent and intravenous iron
Key exclusion criteria (6 listed)
- Body mass index >44.0 kilograms per meter squared (kg/m^2)
- Transfusion within 8 weeks prior to Screening
- Alanine transaminase or total bilirubin >1.25x ULN
- Uncontrolled hypertension
- Class III or IV congestive heart failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AKB-6548Starting dose 1. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol. | Drug | AKB-6548, starting dose 1 |
| AKB-6548Starting dose 2. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol. | Drug | AKB-6548, starting dose 2 |
| AKB-6548Starting dose 3. Oral dose administered three times weekly for 16 weeks. Dose adjustment based on hemoglobin levels as defined in the protocol. | Drug | AKB-6548, starting dose 3 |
Primary outcome
Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average
Time frame: Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8
Change from pre-dose average was calculated by the mid-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits.
Change From Pre-dose Average in Hgb Level to The End-of-study Average
Time frame: Pre-dose, Week 15, and Week 16
Change from pre-dose average was calculated by the end-of-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
Change From Mid-study Average in Hgb Level to The End-of-study Average
Time frame: Week 7, Week 8, Week 15, and Week 16
Change from mid-study average was calculated by the end-of-study average minus the mid-study average. The mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
20 secondary outcomes
Change From Baseline in Hgb
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Hematocrit
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Red Blood Cell (RBC) Count
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Absolute Reticulocyte Count
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Percent Reticulocyte Count
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Reticulocyte Hgb Content
Time frame: Baseline, Week 2, Week 4, Week 8, and Week 16
Change From Baseline in Ferritin
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Hepcidin
Time frame: Baseline, Week 8, and Week 16
Change From Baseline in Total Iron-Binding Capacity (TIBC)
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Transferrin Saturation (TSAT)
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Iron
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy
Time frame: Up to Week 16
Number of Participants Who Received Blood Transfusion Rescue Therapy
Time frame: Up to Week 16
Mean Plasma Concentrations of Vadadustat
Time frame: Pre-dialysis and post-dialysis on Week 2 and Week 16
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite
Time frame: Pre-dialysis and post-dialysis on Week 2 and Week 16
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite
Time frame: Pre-dialysis and post-dialysis on Week 2 and Week 16
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to Week 20
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Time frame: Up to Week 20
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Time frame: Up to Week 20
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings
Time frame: Up to Week 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chief Medical Officer study director
Akebia Therapeutics
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AKB-6548 in people with Anemia and End Stage Renal Disease, run by Akebia Therapeutics at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average (time frame: Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2022.