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

Trial Summary

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.

What data supports the effectiveness of the drug Vadadustat for treating anemia in patients with chronic kidney disease?

Research shows that Vadadustat can safely improve hemoglobin levels and promote better iron use in patients with chronic kidney disease and anemia, without increasing the risk of serious side effects. It has been compared to placebo and another treatment, darbepoetin alfa, and was found to be effective in increasing hemoglobin levels and reducing certain iron-related markers. ^{1 2 3 4 5}

Is Vadadustat safe for treating anemia in chronic kidney disease patients?

Vadadustat is generally considered safe for treating anemia in chronic kidney disease patients, as it does not significantly increase the risk of serious adverse events like heart problems or stroke. However, it may increase the risk of nausea and diarrhea. ^{1 2 3 6 7}

How is the drug Vadadustat different from other treatments for anemia in chronic kidney disease?

Vadadustat is unique because it is an oral medication that works by inhibiting hypoxia-inducible factor prolyl-hydroxylase, which helps increase hemoglobin levels and improve iron utilization in patients with chronic kidney disease-related anemia. Unlike traditional treatments, it does not significantly increase the risk of serious adverse events. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is an investigator-initiated, multi-center, randomized (1:1), open-label, active-controlled, pragmatic study of the safety of vadadustat administered three times per week for the treatment of anemia in in-center hemodialysis patients with End Stage Kidney Disease (ESKD). This study will obtain long-term safety data in a large sample of subjects receiving in-center hemodialysis to support adoption of three times per week vadadustat dosing.

Eligibility Criteria

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 on hemodialysis for kidney failure three times a week.

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

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

Exclusion Criteria

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

I am not taking any medication for anemia or gout.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Vadadustat for Anemia in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease. [2022]

3. Netherlands 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. [2023]

4. Australia 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents. [2023]

6. Australia pubmed.ncbi.nlm.nih.gov

Vadadustat for anemia in chronic kidney disease patients on peritoneal dialysis: A phase 3 open-label study in Japan. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Vadadustat: First Approval. [2021]