AnemiaPhase 2FO2RWARD-2NCT03799627

Study of Vadadustat in Hemodialysis Participants With Anemia Switching From Epoetin Alfa

A Phase 2 study testing Vadadustat, Epoetin Alfa and Vadadustat TIW in people with Anemia and Dialysis-dependent Chronic Kidney Disease, run by Akebia Therapeutics at 41 sites in United States.

Completed

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

Official record

Search all trials

Trial summary

This is a Phase 2 open-label efficacy, safety, and pharmacokinetic/pharmacodynamic (PK/PD) study to evaluate oral Vadadustat for the treatment of anemia in hemodialysis participants converting from Epoetin Alfa therapy. Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Anemia, Dialysis-dependent Chronic Kidney Disease
What is being tested?: Vadadustat, Epoetin Alfa and Vadadustat TIW
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 175 participants
Where: 41 sitesUnited States
Study dates: 31 Jan 2019to 15 Jul 2020
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 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

≥18 years of age, providing informed consent
Receiving chronic, outpatient in-center hemodialysis (TIW) for end-stage renal disease for at least 12 weeks prior to Screening
Maintained on intravenous Epoetin Alfa therapy for 8 weeks prior to and including Screening through Screening Visit 2 (SV2)
Eligibility in the Main study and erythropoiesis-stimulating agent (ESA) hyporesponder parallel study is based on the following mean weekly Epoetin Alfa doses:
Main study: Mean weekly Epoetin Alfa dose <300 Units per kilogram per week (U/kg/week) for 8 weeks prior to SV2;
ESA hyporesponder parallel study: Mean weekly Epoetin Alfa dose ≥300 U/kg/week for 8 weeks prior to SV2

Show all 13Show fewer

Two Hb values measured by the central laboratory at least 4 days apart between Screening Visit 1 (SV1) and SV2 as indicated:.
Main study: 2 Hb values between 8.5 and 11.0 g/dL, inclusive;
ESA hyporesponder parallel study: 2 Hb values between 8.0 and 10.0 grams per deciliter (g/dL), inclusive
Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening
Folate and vitamin B12 measurements ≥ lower limit of normal during Screening
Hemodialysis adequacy as indicated by single-pool Kt/Vurea ≥1.2 using the most recent historical measurement within 8 weeks prior to or during Screening
Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure

Who cannot join

Anemia due to a cause other than chronic kidney disease (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia)
Active bleeding or recent blood loss within 8 weeks prior to randomization
Red blood cell (RBC) transfusion within 8 weeks prior to randomization
Anticipated to discontinue hemodialysis during the study
Judged by the Investigator that the participant is likely to need rescue therapy (ESA administration or RBC transfusion) immediately after enrollment in the study
History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver)

Show all 33Show fewer

Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), or total bilirubin >1.5 x upper limit of normal (ULN) during Screening. Participants with a history of Gilbert's syndrome are not excluded.
Current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of Epoetin Alfa
Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening
History of new or recurrent malignancy within 2 years prior to and during Screening or currently receiving treatment or suppressive therapy for cancer. Participants with treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ are not excluded.
History of deep vein thrombosis or pulmonary embolism within 12 weeks prior to or during Screening
History of hemosiderosis or hemochromatosis
History of prior organ transplantation (participants with a history of failed kidney transplant or corneal transplants are not excluded)
Scheduled organ transplant from a living donor and participants on the kidney transplant wait-list who are expected to receive a transplant within 6 months
History of a prior hematopoietic stem cell or bone marrow transplant (stem cell therapy for knee arthritis is not excluded)
Known hypersensitivity to Vadadustat, Epoetin Alfa, or any of their excipients
Any prior use of a hypoxia-inducible factor prolyl-hydroxylase (HIF-PH) inhibitor or any use of an investigational medication within 30 days or 5 half-lives of the investigational medication (whichever is longer), prior to randomization
For female participants of non-childbearing potential:
inability to confirm surgical sterility (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy) at least 1 month prior to Screening;
not considered post-menopausal (no menses for >1 year with follicle stimulating hormone >40 U/Liter at Screening)
For female participants of childbearing potential:
lack of confirmation of the use of acceptable forms of contraception* for a minimum of one complete menstrual cycle prior to Screening;
positive serum pregnancy test at SV2;
unwilling to use two acceptable forms of contraception* (at least one of which must be a barrier method) starting Baseline/Day 1, throughout the Treatment Period and for 30 days after the final study drug administration
Breastfeeding during Screening or throughout the Treatment Period and for 30 days after the final study drug administration
Donation of ova starting at Screening, throughout the Treatment Period, and for 30 days after the final study drug administration
Male participants who have not had a vasectomy and do not agree to the following: use of an acceptable form of contraception* during the study and for 30 days after the last dose of the study drug; to not donate semen during the study and for at least 30 days after the last dose of Vadadustat
Participants with bilateral native nephrectomy
Any other reason, which in the opinion of the Investigator, would make the participant not suitable for participation in the study
Acceptable forms of contraception include:
Established use of oral, injected or implanted hormonal methods of contraception;
Placement of an intrauterine device or intrauterine system;
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

Trial locations and contacts

41 sites in 1 country.

City, postcode or hospital

41 sites in 1 country

United States41 sites

Research Site
Asheville, North Carolina, 28801
Research Site
Augusta, Georgia, 30909
Research Site
Bridgeport, Connecticut, 06606
Research Site
Canton, Ohio, 44718
Research Site
Chesapeake, Virginia, 23320
Research Site
Coral Gables, Florida, 33134
Research Site
Denver, Colorado, 80230
Research Site
El Paso, Texas, 79915
Research Site
Fresno, California, 93720
Research Site
Granada Hills, California, 91344
Research Site
Hartford, Connecticut, 06762
Research Site
Hollywood, Florida, 33024
Research Site
Houston, Texas, 77004
Research Site
Kansas City, Missouri, 64111
Research Site
Las Vegas, Nevada, 89107
Research Site
Los Angeles, California, 90022
Research Site
Miami, Florida, 33126
Research Site
Miami, Florida, 33134
Research Site
Miami, Florida, 33150
Research Site #1
Minneapolis, Minnesota, 55404
Research Site #2
Minneapolis, Minnesota, 55404
Research Site
Norfolk, Virginia, 23510
Research Site
Northridge, California, 91324
Research Site
Oklahoma City, Oklahoma, 73116
Research Site
Riverside, California, 92501
Research Site
Roseville, Michigan, 48066
Research Site
San Antonio, Texas, 78229
Research Site
San Antonio, Texas, 78258
Research Site #1
San Dimas, California, 91773
Research Site #2
San Dimas, California, 91773
Research Site
San Gabriel, California, 91776
Research Site
Statesboro, Georgia, 30458
Research Site
Tampa, Florida, 33607
Research Site
Tampa, Florida, 33614
Research Site
Tarzana, California, 91356
Research Site
The Bronx, New York, 10461
Research Site
Vacaville, California, 95688
Research Site
Victorville, California, 92394
Research Site
Wauwatosa, Wisconsin, 53226
Research Site
Wilmington, North Carolina, 28401
Research Site
Winter Park, Florida, 32789

Other trials in United States

About this study

Official title: Phase 2, Randomized, Open-Label, Active-Controlled, Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of Oral Vadadustat for the Treatment of Anemia in Hemodialysis Subjects Converting From Epoetin Alfa (FO2RWARD-2)

Read the detailed description

This is a Phase 2, randomized, open-label study to evaluate efficacy and safety of oral Vadadustat for the treatment of anemia in hemodialysis participants converting from Epoetin Alfa therapy. The study will be conducted in two parts running in parallel: Part 1, Main Study in a hemodialysis population on maintenance treatment with Epoetin Alfa; Part 2 is in a hemodialysis population that are erythropoiesis-stimulating agent (ESA) hyporesponders on maintenance treatment with Epoetin Alfa. For all participants (Main and ESA hyporesponder parallel study), the study will include a Screening Period, a Treatment Period, and a Safety Follow-Up Period. PK and PD sampling will be done throughout the study. The aim is to achieve and maintain hemoglobin (Hb) levels within the target range of 10.0 to 11.0 grams per deciliter (g/dL), inclusive, while targeting the middle of the range and minimizing excursions outside the target range.

Conditions: Anemia, Dialysis-dependent Chronic Kidney Disease
Being tested: Vadadustat, Epoetin Alfa, Vadadustat TIW
Keywords: Vadadustat, AKB-6548, Anemia, Chronic kidney disease (CKD), erythropoietin
Medical subject headings: Anemia, Renal Insufficiency, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VadadustatDrug
Also called AKB-6548
Vadadustat Tablets 150 mg
Epoetin AlfaDrug
Also called Procrit, Epogen
Epoetin Alfa
Vadadustat TIWDrug
Oral Vadadustat

Study groups in NCT03799627
Study group	Role	What they receive
Vadadustat	Experimental	The initial dose of Vadadustat (300, 450, or 600 milligrams [mg]) will be based upon the dose of Epoetin Alfa dose participants had received prior to Vadadustat treatment Receives: Drug: Vadadustat
Vadadustat TIW	Experimental	Participants randomized to Vadadustat (Main and erythropoiesis-stimulating agent [ESA] hyporesponder parallel studies) who complete a once-daily dosing regimen treatment period and meet eligibility criteria for transition to three times weekly (TIW) dosing will switch to TIW dosing Receives: Drug: Vadadustat TIW
Epoetin Alfa	Active comparator	Epoetin Alfa Receives: Drug: Epoetin Alfa

What is being measured

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

Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP)
Change from Baseline in Hb value was calculated as the PEP Hb value minus the Baseline Hb value. The PEP value was the average Hb value from Week 10 to Week 12. The Baseline Hb value was defined as the average of the final two Hb values prior to start of dosing on Day 1.
Measured: Baseline; Week 10 to Week 12
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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. An AE 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. TEAEs, defined as AEs that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, are reported.
Measured: Up to Week 24
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Parameters assessed for laboratory values included hematology (excluding the primary and secondary efficacy endpoint results related to Hb), clinical chemistry, lipid profiles, and glucose. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Measured: Up to Week 24
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values
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 vital sign values for clinically significant changes.
Measured: Up to Week 24
Number of Participants Classified as Hb Outliers
The target range for Hb was from 10.0 to 11.0 grams per deciliter (g/dL). Hb outliers included participants with a Hb increase of more than 12.0 g/dL or <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline, and a Hb increase to more than 1.0 g/dL within any 2-week interval during the Study Period.
Measured: Weeks 13 - 20

Secondary outcomes (23)

Number of Participants With Hb Values Within the Target Range at the PEP
The target range for Hb was from 10.0 to 11.0 g/dL, inclusive. The PEP was comprised of Week 10 to Week 12.
Measured: Week 10 to Week 12
Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12
Change from PEP was calculated as the SEP value minus the PEP value. The PEP value was the average Hb value from Week 10 to Week 12. The SEP value was the average Hb value from Week 18 to Week 20. For the Main Study, analysis is presented per dose level according to the starting dose in TIW regimen, as well as being presented as a combined arm for "Vadadustat Total (TIW dosing regimen)". For the ESA Hyporesponder Parallel Study, a starting dose classification for TIW dosing regimen was not applicable due to no participants switching from Vadadustat QD to TIW dosing.
Measured: Week 10 to Week 12; Week 18 to Week 20
Mean Change in Hb Between Baseline and the SEP
Change from Baseline was calculated as the SEP value minus the Baseline value. The Baseline Hb value was defined as the average of the final two Hb values prior to start of dosing on Day 1. The SEP value was the average Hb value from Week 18 to Week 20.
Measured: Baseline; Week 18 to Week 20
Number of Participants With Hb Values Within the Target Range at the SEP
The target range for Hb was from 10.0 to 11.0 g/dL. The SEP was comprised of Week 18 to Week 20.
Measured: Week 18 to Week 20
Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing
The target range for Hb was from 10.0 to 11.0 g/dL. The SEP was comprised of Week 18 to Week 20. For the Main Study, analysis is presented per dose level according to the starting dose in TIW regimen, as well as being presented as a combined arm for "Vadadustat Total (TIW dosing regimen)". For the ESA Hyporesponder Parallel Study, a starting dose classification for TIW dosing regimen was not applicable due to no participants switching from Vadadustat QD to TIW dosing.
Measured: Week 18 to Week 20
Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP
The target range for Hb was from 10.0 to 11.0 g/dL. The PEP was comprised of Week 10 to Week 12.
Measured: Week 10 to Week 12
Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP
The target range for Hb was from 10.0 to 11.0 grams per g/dL. The SEP was comprised of Week 18 to Week 20.
Measured: Week 18 to Week 20
Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation
Iron supplementation was performed to maintain ferritin ≥200 nanograms/milliliters (ng/mL) and transferrin saturation (TSAT) ≥20%.
Measured: Up to Week 20
Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue
ESA rescue therapy was administered in participants with Hb ≥8.5 g/dL, and was stopped when Hb reached ≥9.0 g/dL.
Measured: Up to Week 20
Number of Participants Requiring Red Blood Cell (RBC) Transfusion
RBC transfusion was administered as rescue therapy in the event of an acute or severe loss of blood.
Measured: Up to Week 20
Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group
Blood samples were collected from participants at defined time points for the assessment of EPO concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline; Week 1 (pre-dose), Week 1 +1 (Day 8; pre-dose), Week 11 (pre-dose), and Week 13 (pre-dose)
Mean Change From Baseline in Reticulocyte Count
Blood samples were collected from participants at defined time points for the assessment of reticulocyte count. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline; Week 1, Week 4, Week 8, Week 11, Week 12, Week 13, Week 16, and Week 20
Mean Change From Baseline in Iron Concentration
Blood samples were collected from participants at defined time points for the assessment of iron indices, including iron concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20
Mean Change From Baseline in Ferritin Concentration
Blood samples were collected from participants at defined time points for the assessment of iron indices, including ferritin concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20
Mean Change From Baseline in Total Iron Binding Capacity
Blood samples were collected from participants at defined time points for the assessment of iron indices, including Total Iron Binding Capacity. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20
Mean Change From Baseline in Hepcidin Concentration
Blood samples were collected from participants at defined time points for the assessment of hepcidin concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline; Week 12 and Week 20
Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of Cmax of Vadadustat following a single dose.
Measured: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of AUC and AUC0-24 of Vadadustat following a single dose.
Measured: Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of t1/2 of Vadadustat following a single dose.
Measured: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of Tmax of Vadadustat following a single dose.
Measured: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of λz of Vadadustat following a single dose.
Measured: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of CLss/F of Vadadustat following a single dose.
Measured: Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of Vz/F of Vadadustat following a single dose.
Measured: Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose

Timeline

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

31 Jan 201915 Jul 2020

First posted10 Jan 2019
Study start31 Jan 2019
Primary completion5 Jun 2020
Study completion15 Jul 2020

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.
Publications (1)Papers the sponsor has linked to this study.
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: Randomised
Intervention model: Parallel groups
Model description: Randomized, Open-Label, Active-Controlled
Masking: None (open label)
Enrolment: 175 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03799627
Sponsor's protocol ID: AKB-6548-CI-0025
Acronym: FO2RWARD-2
Status last verified: Sep 2022
First submitted: 3 Dec 2018
Last updated: 29 Sep 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: 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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
The Safety and Efficacy of Daratumumab in Patients With Refractory Aplastic Anemia
Aplastic Anemia, Refractory
Active, not recruitingPhase 1
A Study of YTS109 Cell Injection in Subjects With Relapsed/Refractory Autoimmune Hemolytic Anemia
Autoimmune Hemolytic Anemia, Anti-CD19 STAR T-cell Therapy
Not yet recruitingObservational study
Systematic Intraoperative Cell Salvage in On-Pump Cardiac Surgery Within a Mature Patient Blood Management Programme
Cardiac Surgical Procedures, Blood Transfusion
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
RecruitingObservational study
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
Fanconi Anemia, Inherited Bone Marrow Failure Syndrome

All Anemia trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 2, Randomized, Open-Label, Active-Controlled, Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of Oral Vadadustat for the Treatment of Anemia in Hemodialysis Subjects Converting From Epoetin Alfa (FO2RWARD-2)
ClinicalTrials.gov ID: NCT03799627
Acronym / sponsor ID: FO2RWARD-2 / AKB-6548-CI-0025
Conditions: Anemia, Dialysis-dependent Chronic Kidney Disease
Keywords: Vadadustat, AKB-6548, Anemia, Chronic kidney disease (CKD), erythropoietin
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 175 participants (actual)
Lead sponsor: Akebia TherapeuticsIndustry (pharma, biotech, devices)
Study start: 31 Jan 2019 (actual)
Primary completion: 5 Jun 2020 (actual)
Study completion: 15 Jul 2020 (actual)
First posted: 10 Jan 2019 (actual)
Results: Posted 29 Sep 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: Randomized, Open-Label, Active-Controlled

Arm	Type	Receives
Vadadustat	Experimental	Drug: VadadustatThe initial dose of Vadadustat (300, 450, or 600 milligrams [mg]) will be based upon the dose of Epoetin Alfa dose participants had received prior to Vadadustat treatment
Vadadustat TIW	Experimental	Drug: Vadadustat TIWParticipants randomized to Vadadustat (Main and erythropoiesis-stimulating agent [ESA] hyporesponder parallel studies) who complete a once-daily dosing regimen treatment period and meet eligibility criteria for transition to three times weekly (TIW) dosing will switch to TIW dosing
Epoetin Alfa	Active comparator	Drug: Epoetin AlfaEpoetin Alfa

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

≥18 years of age, providing informed consent
Receiving chronic, outpatient in-center hemodialysis (TIW) for end-stage renal disease for at least 12 weeks prior to Screening
Maintained on intravenous Epoetin Alfa therapy for 8 weeks prior to and including Screening through Screening Visit 2 (SV2)
Eligibility in the Main study and erythropoiesis-stimulating agent (ESA) hyporesponder parallel study is based on the following mean weekly Epoetin Alfa doses:
Two Hb values measured by the central laboratory at least 4 days apart between Screening Visit 1 (SV1) and SV2 as indicated:.

Key exclusion criteria (33 listed)

Anemia due to a cause other than chronic kidney disease (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia)
Active bleeding or recent blood loss within 8 weeks prior to randomization
Red blood cell (RBC) transfusion within 8 weeks prior to randomization
Anticipated to discontinue hemodialysis during the study
Judged by the Investigator that the participant is likely to need rescue therapy (ESA administration or RBC transfusion) immediately after enrollment in the study

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
VadadustatAlso: AKB-6548Vadadustat Tablets 150 mg	Drug	Vadadustat
Epoetin AlfaAlso: Procrit, EpogenEpoetin Alfa	Drug	Epoetin Alfa
Vadadustat TIWOral Vadadustat	Drug	Vadadustat TIW

Primary outcome

Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP)
Time frame: Baseline; Week 10 to Week 12
Change from Baseline in Hb value was calculated as the PEP Hb value minus the Baseline Hb value. The PEP value was the average Hb value from Week 10 to Week 12. The Baseline Hb value was defined as the average of the final two Hb values prior to start of dosing on Day 1.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to Week 24
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. An AE 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. TEAEs, defined as AEs that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, are reported.
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Time frame: Up to Week 24
Parameters assessed for laboratory values included hematology (excluding the primary and secondary efficacy endpoint results related to Hb), clinical chemistry, lipid profiles, and glucose. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values
Time frame: Up to Week 24
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 vital sign values for clinically significant changes.
Number of Participants Classified as Hb Outliers
Time frame: Weeks 13 - 20
The target range for Hb was from 10.0 to 11.0 grams per deciliter (g/dL). Hb outliers included participants with a Hb increase of more than 12.0 g/dL or <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline, and a Hb increase to more than 1.0 g/dL within any 2-week interval during the Study Period.

23 secondary outcomes

Number of Participants With Hb Values Within the Target Range at the PEP
Time frame: Week 10 to Week 12
Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12
Time frame: Week 10 to Week 12; Week 18 to Week 20
Mean Change in Hb Between Baseline and the SEP
Time frame: Baseline; Week 18 to Week 20
Number of Participants With Hb Values Within the Target Range at the SEP
Time frame: Week 18 to Week 20
Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing
Time frame: Week 18 to Week 20
Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP
Time frame: Week 10 to Week 12
Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP
Time frame: Week 18 to Week 20
Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation
Time frame: Up to Week 20
Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue
Time frame: Up to Week 20
Number of Participants Requiring Red Blood Cell (RBC) Transfusion
Time frame: Up to Week 20
Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group
Time frame: Baseline; Week 1 (pre-dose), Week 1 +1 (Day 8; pre-dose), Week 11 (pre-dose), and Week 13 (pre-dose)
Mean Change From Baseline in Reticulocyte Count
Time frame: Baseline; Week 1, Week 4, Week 8, Week 11, Week 12, Week 13, Week 16, and Week 20
Mean Change From Baseline in Iron Concentration
Time frame: Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20
Mean Change From Baseline in Ferritin Concentration
Time frame: Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20
Mean Change From Baseline in Total Iron Binding Capacity
Time frame: Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20
Mean Change From Baseline in Hepcidin Concentration
Time frame: Baseline; Week 12 and Week 20
Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose

Results and safety

Results posted to the registry on 29 Sep 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Low Dose of Epoetin Alfa: Vadadustat 300 mg	35	27
Low Dose of Epoetin Alfa: Vadadustat 450 mg	34	23
Low Dose of Epoetin Alfa: Epoetin Alfa	23	22
High Dose of Epoetin Alfa: Vadadustat 300 mg	18	8
High Dose of Epoetin Alfa: Vadadustat 450 mg	21	12
High Dose of Epoetin Alfa: Vadadustat 600 mg	21	8
High Dose of Epoetin Alfa: Epoetin Alfa	13	10
ESA Hyporesponder: Vadadustat 600 mg	5	3
ESA Hyporesponder: Epoetin Alfa	5	2

Primary outcome: Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP)

Time frame: Baseline; Week 10 to Week 12. Mean (Standard Deviation). Unit: grams per deciliter (g/dL)

Measure	Low Dose of Epoetin Alfa: Vadadustat 300 mg n = 35	Low Dose of Epoetin Alfa: Vadadustat 450 mg n = 34	Low Dose of Epoetin Alfa: Epoetin Alfa n = 23	High Dose of Epoetin Alfa: Vadadustat 300 mg n = 18	High Dose of Epoetin Alfa: Vadadustat 450 mg n = 21	High Dose of Epoetin Alfa: Vadadustat 600 mg n = 21	High Dose of Epoetin Alfa: Epoetin Alfa n = 13	ESA Hyporesponder: Vadadustat 600 mg n = 5	ESA Hyporesponder: Epoetin Alfa n = 5
Baseline	10.223 (0.5805)	10.059 (0.6769)	10.165 (0.6806)	9.778 (0.6832)	10.288 (0.5445)	10.095 (0.7150)	9.950 (0.7950)	9.530 (0.2864)	9.620 (0.6925)
Change from Baseline at PEP	-0.371 (0.8920)	0.072 (1.1353)	0.160 (0.7519)	-0.911 (1.3515)	-0.284 (1.0383)	-0.418 (1.2752)	0.268 (1.0087)	-0.671 (0.7643)	-0.290 (1.7730)

Population analysed: Randomized Population: All randomized participants. Analysis of this population was based on the randomized treatment.

Primary outcome: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Time frame: Up to Week 24. Count of participants. Unit: Participants

Measure	Low Dose of Epoetin Alfa: Vadadustat 300 mg n = 34	Low Dose of Epoetin Alfa: Vadadustat 450 mg n = 35	Low Dose of Epoetin Alfa: Epoetin Alfa n = 23	High Dose of Epoetin Alfa: Vadadustat 300 mg n = 18	High Dose of Epoetin Alfa: Vadadustat 450 mg n = 21	High Dose of Epoetin Alfa: Vadadustat 600 mg n = 21	High Dose of Epoetin Alfa: Epoetin Alfa n = 13	ESA Hyporesponder: Vadadustat 600 mg n = 5	ESA Hyporesponder: Epoetin Alfa n = 5
Value	18	27	13	12	14	13	9	5	3

Population analysed: Safety Population: all participants in the Randomized Population who received at least 1 dose of study drug. Analysis of this population was based on actual treatment received. Participants who received Vadadustat and Epoetin Alfa in error were classified by the more frequently received drug. One participant randomized to the Low Dose of Epoetin Alfa: Vadadustat 300 mg arm inadvertently received 450 mg of Vadadustat.

Primary outcome: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values

Time frame: Up to Week 24. Count of participants. Unit: Participants

Measure	Low Dose of Epoetin Alfa: Vadadustat 300 mg n = 34	Low Dose of Epoetin Alfa: Vadadustat 450 mg n = 35	Low Dose of Epoetin Alfa: Epoetin Alfa n = 23	High Dose of Epoetin Alfa: Vadadustat 300 mg n = 18	High Dose of Epoetin Alfa: Vadadustat 450 mg n = 21	High Dose of Epoetin Alfa: Vadadustat 600 mg n = 21	High Dose of Epoetin Alfa: Epoetin Alfa n = 13	ESA Hyporesponder: Vadadustat 600 mg n = 5	ESA Hyporesponder: Epoetin Alfa n = 5
Value	0	0	0	0	0	0	0	0	0

Population analysed: Safety Population. Analysis of this population was based on the actual treatment received. Participants who received Vadadustat and Epoetin Alfa in error were classified by the more frequently received drug. One participant randomized to the Low Dose of Epoetin Alfa: Vadadustat 300 mg arm inadvertently received 450 mg of Vadadustat.

Primary outcome: Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values

Time frame: Up to Week 24. Count of participants. Unit: Participants

Measure	Low Dose of Epoetin Alfa: Vadadustat 300 mg n = 34	Low Dose of Epoetin Alfa: Vadadustat 450 mg n = 35	Low Dose of Epoetin Alfa: Epoetin Alfa n = 23	High Dose of Epoetin Alfa: Vadadustat 300 mg n = 18	High Dose of Epoetin Alfa: Vadadustat 450 mg n = 21	High Dose of Epoetin Alfa: Vadadustat 600 mg n = 21	High Dose of Epoetin Alfa: Epoetin Alfa n = 13	ESA Hyporesponder: Vadadustat 600 mg n = 5	ESA Hyporesponder: Epoetin Alfa n = 5
Value	0	0	0	0	0	0	0	0	0

23 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Week 24 (from first dose of study drug to last dose + 4 weeks of follow-up). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Low Dose of Epoetin Alfa: Vadadustat 300 mg	9 of 34 (26.5%)	11 of 34 (32.4%)	0 of 34
Low Dose of Epoetin Alfa: Vadadustat 450 mg	7 of 35 (20%)	20 of 35 (57.1%)	0 of 35
Low Dose of Epoetin Alfa: Epoetin Alfa	5 of 23 (21.7%)	10 of 23 (43.5%)	0 of 23
High Dose of Epoetin Alfa: Vadadustat 300 mg	8 of 18 (44.4%)	9 of 18 (50%)	1 of 18
High Dose of Epoetin Alfa: Vadadustat 450 mg	6 of 21 (28.6%)	9 of 21 (42.9%)	1 of 21
High Dose of Epoetin Alfa: Vadadustat 600 mg	10 of 21 (47.6%)	10 of 21 (47.6%)	1 of 21
High Dose of Epoetin Alfa: Epoetin Alfa	5 of 13 (38.5%)	8 of 13 (61.5%)	1 of 13
ESA Hyporesponder: Vadadustat 600 mg	4 of 5 (80%)	4 of 5 (80%)	0 of 5
ESA Hyporesponder: Epoetin Alfa	3 of 5 (60%)	2 of 5 (40%)	0 of 5

Limitations and caveats (from the sponsor): Conclusions were drawn from results of the Main Study (n=165). As the sample size in the Erythropoiesis-stimulating Agent (ESA) Hyporesponder Parallel Study (n=10) was small in both the Vadadustat and Epoetin Alfa treatment groups, these results did not allow to meaningful interpretation of the data.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36005278Natale 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.
Individual participant dataSharing planned: No

Related trials for Anemia

RecruitingPhase 1/2
The Safety and Efficacy of Daratumumab in Patients With Refractory Aplastic Anemia
Aplastic Anemia, Refractory
Active, not recruitingPhase 1
A Study of YTS109 Cell Injection in Subjects With Relapsed/Refractory Autoimmune Hemolytic Anemia
Autoimmune Hemolytic Anemia, Anti-CD19 STAR T-cell Therapy
Not yet recruitingObservational study
Systematic Intraoperative Cell Salvage in On-Pump Cardiac Surgery Within a Mature Patient Blood Management Programme
Cardiac Surgical Procedures, Blood Transfusion
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
RecruitingObservational study
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
Fanconi Anemia, Inherited Bone Marrow Failure Syndrome

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

41 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 Vadadustat, Epoetin Alfa and Vadadustat TIW in people with Anemia and Dialysis-dependent Chronic Kidney Disease, run by Akebia Therapeutics at 41 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 13 inclusion and 33 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 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 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 29 Sep 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?

Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) (time frame: Baseline; Week 10 to Week 12). The study lists 5 primary outcomes in all. 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 NCT03799627, which also lists 1 linked publication.

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 29 Sep 2022.