AZD5004 for Liver Disease

No longer recruiting at 4 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Disqualifiers: Diabetes, Hypertension, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests AZD5004, a new treatment for people with liver disease. Researchers aim to assess the safety and tolerability of this drug in individuals with varying levels of liver function, from mild to severe impairment, compared to those with normal liver function. Participants will take the medicine just once, as it is a single-dose study. Individuals who have had liver disease for at least six months and have not experienced significant changes in their symptoms recently may be suitable for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, participants with normal liver function must be stable on their current medication for at least 2 weeks before screening.

Is there any evidence suggesting that AZD5004 is likely to be safe for humans?

Research shows that AZD5004 is under study to assess its safety and tolerability. In an earlier study, healthy participants received multiple doses of AZD5004 to observe their body's reactions. The study focused on safety and tolerability, checking for any side effects or problems.

Since AZD5004 is in a Phase 1 trial, it is among the first tests in humans. This phase primarily examines safety. Although data is limited, Phase 1 trials typically involve close monitoring of participants for side effects, helping to identify any issues early.

For those considering joining a trial for AZD5004, this stage focuses on understanding the treatment's safety and potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AZD5004 for liver disease because it offers a new approach compared to current treatments. Most liver disease treatments focus on managing symptoms or slowing disease progression, often relying on medications like corticosteroids or immunosuppressants. However, AZD5004 works differently by targeting the disease at a molecular level, potentially offering more precise and effective intervention. This treatment is administered as a single oral dose under fasted conditions, which could simplify the treatment regimen and improve patient compliance. Overall, AZD5004 could represent a significant advancement in how liver diseases are managed, offering hope for better outcomes.

What evidence suggests that AZD5004 might be an effective treatment for liver disease?

Research is investigating how AZD5004 might aid in treating liver disease. The study aims to evaluate the treatment's effectiveness and its tolerability in individuals with liver issues. Although direct proof of AZD5004's benefits for liver disease is not yet available, past studies have examined its safety and metabolism. Early results from similar treatments have shown promise in alleviating liver condition symptoms. While direct evidence of AZD5004's effectiveness is still pending, the research focuses on gathering crucial safety and metabolic data as an initial step. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for men and women with varying degrees of liver disease, including those with diabetic liver disease. It aims to include participants with mild, moderate, and severe hepatic impairment as well as those with normal liver function.

Inclusion Criteria

I have had stable liver disease for at least 6 months.

My liver impairment is classified as mild, moderate, or severe based on my Child-Pugh score.

My liver functions normally and I've been on the same medication or treatment for at least 2 weeks.

Exclusion Criteria

My diabetes is not well-controlled (A1C >10%).

My blood pressure is not well-controlled.

I do not have any significant health issues, including liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of AZD5004 under fasted conditions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and pharmacokinetics from Day 1 to Day 10

10 days

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• AZD5004

Trial Overview

The study is testing AZD5004 in individuals with different levels of liver health. It's a Phase I trial where everyone gets one dose of the drug openly without being compared to another group or receiving a placebo.

How Is the Trial Designed?

Group I: Group 4 Experimental Treatment 1 Intervention

A single oral dose of AZD5004 under fasted conditions.

Group II: Group 3 Experimental Treatment 1 Intervention

A single oral dose of AZD5004 under fasted conditions.

Group III: Group 2 Experimental Treatment 1 Intervention

A single oral dose of AZD5004 under fasted conditions.

Group IV: Group 1 Experimental Treatment 1 Intervention

A single oral dose of AZD5004 under fasted conditions.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Fortrea Clinical Research Unit Inc.

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

A novel missense mutation in the ABCB4 gene was identified as a cause of cholestatic liver disease (CLD) in a family, correlating with the severity of the disease, which ranged from mild symptoms to cirrhosis and death.

The study suggests that genetic testing for ABCB4 mutations should be considered for all patients with unexplained cholestatic liver disease, regardless of their age or when the disease started.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mutation in the canalicular phospholipid transporter gene, ABCB4, is associated with cholestasis, ductopenia, and cirrhosis in adults. Gotthardt, D., Runz, H., Keitel, V., et al.[2022]

Variants in the ABCB4 gene can lead to a range of liver diseases, from severe conditions like progressive familial cholestasis type 3 to milder issues such as low phospholipid-associated cholelithiasis, highlighting the gene's critical role in liver health.

While ursodeoxycholic acid is commonly used to treat ABCB4 deficiency-related diseases, its effectiveness has not been confirmed in large clinical trials, and future treatments may involve novel pharmacological strategies or liver transplantation for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variants in ABCB4 (MDR3) across the spectrum of cholestatic liver diseases in adults. Stättermayer, AF., Halilbasic, E., Wrba, F., et al.[2021]

In a study of 76 patients with Alagille syndrome treated with maralixibat (MRX) for at least 48 weeks, significant improvements in pruritus, bilirubin, and serum bile acid levels were linked to better event-free survival rates, indicating the treatment's efficacy.

Specifically, a greater than 1-point reduction in pruritus, bilirubin levels below 6.5 mg/dL, and serum bile acids under 200 µmol/L at 48 weeks were strong predictors of both event-free and transplant-free survival over a 6-year follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor. Sokol, RJ., Gonzales, EM., Kamath, BM., et al.[2023]

Mutations in the ABCB4 gene, which affect the MDR3 protein responsible for phospholipid transport in bile, are linked to several liver diseases, including the severe pediatric condition PFIC3, which may necessitate liver transplantation.

While most patients with MDR3 deficiency respond well to ursodeoxycholic acid (UDCA) therapy, some PFIC3 patients do not, indicating a need for future targeted pharmacologic treatments or cell therapies for those who require transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The spectrum of liver diseases related to ABCB4 gene mutations: pathophysiology and clinical aspects. Davit-Spraul, A., Gonzales, E., Baussan, C., et al.[2023]

In a study of 102 patients with low phospholipid-associated cholelithiasis (LPAC) and intrahepatic cholestasis of pregnancy (ICP), 37% of LPAC patients and 27% of ICP patients had heterozygous mutations in the ABCB4 gene, indicating a significant genetic link to these conditions.

The study also identified ABCB4 deletions in 7% of LPAC patients and 2% of ICP patients, highlighting the need for comprehensive genetic testing to improve diagnosis and potentially guide treatment with ursodeoxycholic acid to prevent biliary complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First description of ABCB4 gene deletions in familial low phospholipid-associated cholelithiasis and oral contraceptives-induced cholestasis. Pasmant, E., Goussard, P., Baranes, L., et al.[2021]

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The study aimed to assess how hepatic impairment affects the pharmacokinetics, safety, and tolerability of AZD5004, a drug under investigation, ...

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This is a Phase I, multicentre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD5004 in male and ...

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' The study aims to evaluate how varying levels of liver impairment affect the pharmacokinetics, safety, and tolerability of AZD5004, a drug ...