AZD2389 for Liver Disease

(CAMPOLINA Trial)

Recruiting at 3 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AstraZeneca

Disqualifiers: HIV, Severe allergy, Dermatological disorders, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine the safety and tolerability of AZD2389 in participants with hepatic impairment and participants with normal hepatic function.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

How does the drug AZD2389 differ from other treatments for liver disease?

The research does not provide specific information about AZD2389, so its unique aspects compared to other liver disease treatments are not clear from the available data. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with stable liver impairment or those who are healthy, weighing at least 50 kg with a BMI of 18.0-42.0 kg/m2. It's not for people with severe allergies, HIV, serious skin conditions, or kidney function below a certain level (eGFR <60 mL/min/1.73 m2).

Inclusion Criteria

My liver condition is stable.

Healthy: Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests.

I weigh at least 50 kg and my BMI is between 18.0 and 42.0.

Exclusion Criteria

History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity

Positive test for HIV at screening

History of severe dermatological disorders

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of AZD2389 and are monitored for pharmacokinetics, safety, and tolerability

48 hours

1 visit (in-patient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AZD2389 (Other)

Trial Overview The study tests AZD2389's effects on individuals with different levels of liver health to understand its safety and how the body processes it.

Participant Groups

Group I: Cohort 4 Experimental Treatment 1 Intervention

Participants with severe hepatic impairment (CP C classification)

Group II: Cohort 3 Experimental Treatment 1 Intervention

Participants with moderate hepatic impairment (CP B classification)

Group III: Cohort 2 Experimental Treatment 1 Intervention

Participants with mild hepatic impairment (CP A classification)

Group IV: Cohort 1 Experimental Treatment 1 Intervention

Participants with normal hepatic function (sex-, age-, and body mass index \[BMI\]-matched)

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

Findings from Research

Gene therapy using the AAV-hZFYVE19 vector significantly reduced liver injury markers and improved liver conditions in a mouse model of ZFYVE19 deficiency, particularly at a low dose of 1 × 10^11 vg/kg.

However, higher doses of the AAV-hZFYVE19 vector (5 × 10^12 vg/kg) led to a loss of therapeutic benefits and even worsened liver conditions, indicating that optimal levels of ZFYVE19 expression are crucial for safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of Portal-Tract Fibrosis in Zfyve19-/- Mouse Model with Adeno-Associated Virus Vector Delivering ZFYVE19. Zhang, Y., Tang, D., Wang, L., et al.[2023]

A case of severe liver disease due to Alpha-1 Antitrypsin (AAT) deficiency was confirmed through histological examination and immunostaining, highlighting the importance of accurate diagnosis in liver conditions.

Successful liver transplantation reversed the effects of the disease, demonstrating that transplantation can be an effective treatment for advanced liver disease associated with AAT deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

End-stage liver disease in a 31-year-old man. Sherman, KE., Goodman, ZD.[2004]

In a study of 23 adults with severe emphysema due to alpha1-antitrypsin deficiency (PiZZ phenotype), 87% were found to have chronic liver disease based on liver biopsy results, indicating a high prevalence of liver involvement in these patients.

Only 8.7% of the patients exhibited severe chronic liver disease, suggesting that while liver histology may show involvement, severe liver dysfunction is relatively rare among those evaluated for lung transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver Involvement in Patients With PiZZ-Emphysema, Candidates for Lung Transplantation. Morer, L., Choudat, L., Dauriat, G., et al.[2023]

In a study of 11 adults with severe alpha1-antitrypsin deficiency but no liver disease symptoms, liver function tests showed no signs of liver damage or abnormal protein synthesis, despite low alpha1-antitrypsin levels.

The hepatic endoplasmic reticulum, which is known to be affected in this condition, did not show impaired function as tested by the aminopyrine breath test, suggesting that liver function may remain intact in the absence of clinical liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver function in asymptomatic adult individuals with severe alpha1-antitrypsin deficiency (Pi Z). Larsson, C., Eriksson, S.[2019]

A patient with a rare genetic condition called homozygous ZZ alpha1-antitrypsin deficiency developed a mixed type of liver cancer (hepatocellular and cholangiolar carcinoma) despite having a noncirrhotic liver.

This case suggests a potential causal link between alpha1-antitrypsin deficiency and the increased risk of liver tumors, highlighting the need for further investigation into this relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha1-antitrypsin deficiency and hepatic carcinoma. Schleissner, LA., Cohen, AH.[2004]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prevention of Portal-Tract Fibrosis in Zfyve19-/- Mouse Model with Adeno-Associated Virus Vector Delivering ZFYVE19. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

End-stage liver disease in a 31-year-old man. [2004]

3. United States pubmed.ncbi.nlm.nih.gov

Liver Involvement in Patients With PiZZ-Emphysema, Candidates for Lung Transplantation. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Liver function in asymptomatic adult individuals with severe alpha1-antitrypsin deficiency (Pi Z). [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Alpha1-antitrypsin deficiency and hepatic carcinoma. [2004]