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AnemiaPhase 2NCT01381094

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

A Phase 2 study testing AKB-6548 in people with Anemia and Kidney Disease, run by Akebia Therapeutics at 28 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the dose response (efficacy), pharmacodynamic response, pharmacokinetics, safety, and tolerability of orally administered AKB-6548 in pre-dialysis participants with anemia with repeat dosing for 42 days. Read more about this study

Who is it for?
Ages 18 to 79 years
Conditions the study is for
Anemia, Kidney Disease
What is being tested?
AKB-6548
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
93 participants
Where
28 sitesUnited States
Study dates
15 Jun 2011to 16 Feb 2012
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 of age, inclusive
  • Chronic Kidney Disease (eGFR <60 mL/min), not yet on dialysis
  • Hemoglobin (Hgb) ≤ 10.5 g/dL
  • Transferring saturation ≥ 20%
  • Ferritin ≥ 50 ng/mL

Who cannot join

  • Body mass index >42
  • 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 11 weeks prior to the Screening visit
  • Participants meeting the criteria of ESA resistance within the previous 4 months
  • Individual doses of intravenous iron of greater than 250 mg within the past 21 days
Show all 12Show fewer
  • Aspartate aminotransferase or alanine aminotransferase >1.8x upper limit of normal (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

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

United States28 sites
  • Study site

    Augusta, Georgia

  • Study site

    Austin, Texas

  • Study site

    Bethpage, New York

  • Study site

    Coral Springs, Florida

  • Study site

    Covina, California

  • Study site

    Detroit, Michigan

  • Study site

    Fort Worth, Texas

  • Study site

    Houston, Texas

  • Study site

    Knoxville, Tennessee

  • Study site

    Lauderdale Lakes, Florida

  • Study site

    Los Angeles, California

  • Study site

    Lynwood, California

  • Study site

    Macon, Georgia

  • Study site

    Miami, Florida

  • Study site

    Mineola, New York

  • Study site

    Ocala, Florida

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Pine Bluff, Arkansas

  • Study site

    Pontiac, Michigan

  • Study site

    Riverside, California

  • Study site

    San Antonio, Texas

  • Study site

    San Dimas, California

  • Study site

    Shreveport, Louisiana

  • Study site

    Springfield, Massachusetts

  • Study site

    Warren, Michigan

  • Study site

    Whittier, California

  • Study site

    Wichita, Kansas

  • Study site

    Wilmington, North Carolina

Other trials in United States

About this study

Official title: Phase 2a Randomized, Double-Blind, Placebo-Controlled, Dose Range Study to Assess the Pharmacodynamic Response, Pharmacokinetics, Safety, and Tolerability of 42-Day Repeat Oral Doses of AKB-6548 in Subjects With Anemia Secondary to Chronic Kidney Disease (CKD), Stages 3 and 4

The purpose of this study is to evaluate the dose response (efficacy), pharmacodynamic response, pharmacokinetics, safety, and tolerability of orally administered AKB-6548 in pre-dialysis participants with anemia with repeat dosing for 42 days.

Being tested
AKB-6548, Placebo
Keywords
anemia, chronic kidney disease, CKD, chronic renal insufficiency, renal impairment, erythropoietin, safety, efficacy, tolerability, pharmacokinetics
Medical subject headings
Anemia, Kidney Diseases, 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

    oral dose administered once daily for 42 days

  • PlaceboDrug

    oral Placebo administered once daily for 42 days

Study groups in NCT01381094
Study groupRoleWhat they receive
AKB-6548 240 mgExperimentalNot described
Receives: Drug: AKB-6548
AKB-6548 370 mgExperimentalNot described
Receives: Drug: AKB-6548
AKB-6548 500 mgExperimentalNot described
Receives: Drug: AKB-6548
AKB-6548 630 mgExperimentalNot described
Receives: Drug: AKB-6548
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)

    Absolute change from Baseline was calculated as the Week 6 (end of treatment) value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing. If there was only one measurement prior to dosing, this measurement served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.

    Measured: Baseline, Week 6

Secondary outcomes (28)
  1. Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.

    Measured: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

  2. Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated HCT concentration increased.

    Measured: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

  3. Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated RBC count increased.

    Measured: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

  4. Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte count increased.

    Measured: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

  5. Change From Baseline in Reticulocyte Hgb Content at Week 6

    Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte Hgb content increased.

    Measured: Baseline, Week 6

  6. Maximum Change From Baseline in Hgb

    Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.

    Measured: Baseline; up to Week 8

  7. Maximum Change From Baseline in HCT

    Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that HCT concentration increased.

    Measured: Baseline; up to Week 8

  8. Maximum Change From Baseline in RBC Count

    Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline RBC Count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that RBC count increased.

    Measured: Baseline; up to Week 8

  9. Maximum Change in Absolute Reticulocyte Count From Baseline

    Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline absolute reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that reticulocyte count increased.

    Measured: Baseline; up to Week 8

  10. Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period

    Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Up to Week 6 (End of the Dosing Period)

  11. Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period

    Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Up to Week 6 (End of The Dosing Period)

  12. Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period

    Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Up to Week 6 (End of The Dosing Period)

  13. Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period

    Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline RBC Count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Up to Week 6 (End of The Dosing Period)

  14. Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period

    Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline reticulocytes count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Up to Week 6 (End of The Dosing Period)

  15. Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline total iron was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

  16. Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Unsaturated Iron Binding Capacity was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

  17. Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron saturation was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

  18. Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

  19. Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8)

  20. Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8)

    Change from Baseline was calculated as the visit value minus the Baseline value. Baseline erythropoietin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8)

  21. Change From Baseline in Hepcidin at Week 6

    Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline hepcidin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.

    Measured: Baseline, Week 6

  22. Mean Plasma Vadadustat Concentrations on Week 2 and Week 4

    Plasma samples were collected for the analysis.

    Measured: Week 2: Pre-dose and post-dose; Week 4: Pre-dose

  23. Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4

    Plasma samples were collected for the analysis.

    Measured: Week 2: Pre-dose; Week 4: Pre-dose

  24. 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, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect.

    Measured: Up to Week 8 (Follow-up Visit 2 weeks after last dose)

  25. Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter

    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 8 (Follow-up Visit 2 weeks after last dose)

  26. Number of Participants With Clinically Significant Abnormal 12-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. Clinical significance is determined by the investigator. The investigator was responsible for reviewing laboratory results for clinical significance.

    Measured: Up to Week 8 (Follow-up Visit 2 weeks after last dose)

  27. 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).

    Measured: Baseline, Week 6

  28. Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values

    Parameters assessed for laboratory values included hematology, serum chemistry, C-reactive protein, DHEA-S, VEGF, and cystatin C. The investigator was responsible for reviewing laboratory results for clinically significant changes.

    Measured: Up to Week 8 (Follow-up Visit 2 weeks after last dose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2011 (estimated)
  2. Study start15 Jun 2011
  3. Primary completion16 Feb 2012
  4. Study completion16 Feb 2012

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01381094
Sponsor's protocol ID
AKB-6548-CI-0005
Status last verified
Jun 2022
First submitted
23 Jun 2011
Last updated
1 Jul 2022
Data monitoring committee
No
Individual data sharing
No

Publications

  • Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

    PubMed 36005278
  • Martin ER, Smith MT, Maroni BJ, Zuraw QC, deGoma EM. Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease. Am J Nephrol. 2017;45(5):380-388. doi: 10.1159/000464476. Epub 2017 Mar 25.

    PubMed 28343225

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AKB-6548 in people with Anemia and Kidney Disease, run by Akebia Therapeutics at 28 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 5 inclusion and 12 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 28 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. Some participants in this study may receive a placebo. 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?

Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) (time frame: Baseline, Week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01381094, which also lists 2 linked publications.

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.

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