Vadadustat for Anemia of Chronic Kidney Disease

(VOICE Trial)

Recruiting at 4 trial locations

Overseen By Stephanie Brillhart, MSCI

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: USRC Kidney Research

Must be taking: Erythropoiesis-stimulating agents

Must not be taking: Hypoxia-inducible factors, OAT1/OAT3 inhibitors

Disqualifiers: Cirrhosis, Acute liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Long-term

2200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of vadadustat, a new treatment for anemia in individuals with end-stage kidney disease undergoing hemodialysis. Anemia occurs when the body lacks enough red blood cells to carry oxygen, often causing extreme fatigue. The study compares vadadustat, taken three times a week, to standard treatments like EPOGEN or Aranesp. Ideal candidates for this trial are those on hemodialysis three times a week for end-stage kidney disease and who are already using or can use medications to boost red blood cells. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs like probenacid, rifampicin, gemfibrozil, or teriflunomide while participating.

Is there any evidence suggesting that vadadustat is likely to be safe for humans?

Research has shown that vadadustat can safely increase hemoglobin (Hb) levels and help the body use iron more effectively in patients with chronic kidney disease (CKD) who have anemia. Importantly, it achieves this without causing many serious side effects. In previous studies, participants did not experience many serious problems when taking vadadustat.

Vadadustat is being developed specifically to treat anemia in adults with CKD who are on dialysis. As it is in a later stage of clinical trials, it has already undergone earlier tests to ensure safety for humans. This typically means that any major safety issues have likely been identified and addressed. Always consult a healthcare provider to understand what this means for individual circumstances. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Vadadustat is unique because it offers a fresh approach to treating anemia in chronic kidney disease by targeting the body's oxygen-sensing pathway. Unlike standard treatments like Epoetin alfa or Darbepoetin alfa, which stimulate red blood cell production directly, Vadadustat works by stabilizing a protein that encourages the body to produce its own erythropoietin naturally. This mechanism could potentially lead to more stable hemoglobin levels with fewer side effects. Researchers are excited because this method might reduce the need for frequent injections, providing a more convenient oral option for patients.

What evidence suggests that vadadustat might be an effective treatment for anemia in patients with end stage kidney disease?

Research has shown that vadadustat, which participants in this trial may receive, can effectively raise hemoglobin levels in people with anemia caused by chronic kidney disease. Studies have found that vadadustat helps the body use iron better without causing more serious side effects than other treatments. This medication works by stabilizing a protein that aids in producing more red blood cells. Vadadustat has proven effective for patients both on dialysis and those who are not. Overall, patients using vadadustat have experienced improvements in managing anemia related to kidney disease. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with anemia due to chronic kidney disease who are undergoing in-center hemodialysis. Participants must be stable on their current erythropoiesis-stimulating agent treatment. Those with uncontrolled hypertension, recent blood clots, or known hypersensitivity to vadadustat cannot join.

Inclusion Criteria

I am eligible for or currently receiving treatment to help my body make more red blood cells.

I am on hemodialysis for kidney failure three times a week.

Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure.

Exclusion Criteria

I am not taking any medication for anemia or gout.

I cannot take vadadustat or its ingredients due to health reasons.

Pregnant at time of consent (per subject self-report)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vadadustat or standard of care treatment for anemia in in-center hemodialysis patients

Long-term

3 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vadadustat

Trial Overview The study compares the safety of a drug called vadadustat, given three times a week, against other drugs that stimulate red blood cell production. It's designed to see if vadadustat can be safely adopted for regular use in treating anemia in patients receiving hemodialysis.

How Is the Trial Designed?

Group I: Vadadustat Experimental Treatment 1 Intervention

Vadadustat, 300 mg tablets, administered orally three times per week

Group II: Erythropoiesis-stimulating agent (ESA) - Standard of Care (SOC) Active Control 1 Intervention

Epoetin alfa (EPOGEN), Methoxy polyethylene glycol-epoetin beta (Mircera), or Darbepoetin alfa (Aranesp) administered as per standard of care

Vadadustat is already approved in United States, Japan for the following indications:

Approved in United States as Vafseo for:

• Anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months

Approved in Japan as Vafseo for:

• Anemia due to chronic kidney disease (CKD)

Who Is Running the Clinical Trial?

USRC Kidney Research

Lead Sponsor

Trials

5

Recruited

3,000+

Akebia Therapeutics

Industry Sponsor

Trials

35

Recruited

12,400+

Published Research Related to This Trial

Vadadustat is comparable to darbepoetin alfa in raising hemoglobin levels in patients with nondialysis-dependent chronic kidney disease (NDD-CKD), showing no significant difference in efficacy over a treatment duration of 20-36 weeks.

In dialysis-dependent chronic kidney disease (DD-CKD) patients, vadadustat was less effective than darbepoetin alfa in achieving target hemoglobin levels, but both treatments had similar safety profiles regarding the need for red blood cell transfusions and serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vadadustat compared to darbepoetin alfa on anemia in patients with chronic kidney disease: a meta-analysis. Huang, Q., Liao, Z., Liu, X., et al.[2023]

Vadadustat effectively increased and maintained hemoglobin levels in Japanese patients with chronic kidney disease-associated anemia on hemodialysis, achieving an average hemoglobin of 10.75 g/dL over 24 weeks.

The treatment was generally well-tolerated, with the most common adverse event being shunt stenosis in 25% of patients, and only mild adverse drug reactions like diarrhea and vomiting occurring in 8.3% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3, open-label, single-arm study of vadadustat for anemia in chronic kidney disease for Japanese patients on hemodialysis not receiving erythropoiesis-stimulating agents. Nangaku, M., Kondo, K., Takabe, S., et al.[2022]

Vadadustat effectively maintained hemoglobin levels within the target range of 11.0-13.0 g/dL in 42 Japanese patients with chronic kidney disease undergoing peritoneal dialysis over a 24-week period.

The treatment was generally well tolerated, with the most common adverse event being catheter site infections, which were not related to vadadustat, highlighting its safety profile in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vadadustat for anemia in chronic kidney disease patients on peritoneal dialysis: A phase 3 open-label study in Japan. Nangaku, M., Kondo, K., Takabe, S., et al.[2022]

Vadadustat is a prolyl hydroxylase inhibitor developed for treating anemia in patients with chronic kidney disease (CKD) and has received approval in Japan for this indication.

The drug is being collaboratively developed for commercialization in multiple regions, including the USA and EU, with regulatory submissions planned, indicating its potential for broader availability and use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vadadustat: First Approval. Markham, A.[2021]

Vadadustat significantly increases hemoglobin levels and response rates in patients with anemia due to chronic kidney disease (CKD), based on a meta-analysis of 10 randomized controlled trials involving 8,438 participants.

While vadadustat improves hemoglobin and iron utilization, it is associated with a higher risk of mild side effects like nausea and diarrhea, but does not increase the risk of serious adverse events such as all-cause mortality or cardiac events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Vadadustat for Anemia in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Xiong, L., Zhang, H., Guo, Y., et al.[2022]

In a phase 2a trial involving 93 adults with anemia due to chronic kidney disease (CKD), vadadustat significantly increased hemoglobin levels in a dose-dependent manner compared to placebo after 6 weeks of treatment.

Vadadustat also improved iron mobilization by increasing total iron-binding capacity and decreasing ferritin and hepcidin levels, with a safety profile similar to that of the placebo group, indicating it may be a promising treatment option for anemia in CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease. Martin, ER., Smith, MT., Maroni, BJ., et al.[2022]

In a Phase 2 trial involving 94 hemodialysis patients, vadadustat maintained stable hemoglobin levels without significant changes from pre-baseline averages, suggesting it may be a viable alternative to epoetin alfa for managing anemia.

The study reported a high incidence of adverse events (83%), primarily mild symptoms like nausea and diarrhea, but no serious adverse events or deaths were linked to vadadustat, indicating a favorable safety profile for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents. Haase, VH., Chertow, GM., Block, GA., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5452283/

Clinical Trial of Vadadustat in Patients with Anemia Secondary ... Vadadustat increased Hb levels and improved biomarkers of iron mobilization and utilization in patients with anemia secondary to stage 3 or 4 CKD.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02892149

NCT02892149 | Efficacy and Safety Study to Evaluate ... Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Dialysis-dependent Chronic Kidney Disease (DD-CKD).

3. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.795214/full

Efficacy and Safety of Vadadustat for Anemia in Patients ... Vadadustat may safely improve Hb levels and promote iron utilization in CKD patients with anemia without increasing the incidence of serious adverse events.

4. sciencedirect.com sciencedirect.com/science/article/pii/S002235652400332X

Preclinical Characterization of Vadadustat (AKB-6548), an ... Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Kidney Int, 90 (2016), pp. 1115 ...

5. kidney-international.org kidney-international.org/article/S0085-2538(16)30357-X/fulltext

Vadadustat, a novel oral HIF stabilizer, provides effective ... Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Pablo E. Pergola. Pablo E.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/215192Orig1s000OtherR.pdf

215192Orig1s000 OTHER REVIEW(S) - accessdata.fda.gov The proposed indication for vadadustat is “for the treatment of anemia associated with chronic kidney disease (CKD) in adults on dialysis.” The ...