Inaxaplin for Liver Disease

No longer recruiting at 3 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Smoking, Acute illness, 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 a new treatment called Inaxaplin (IXP) to evaluate its safety and how the body processes it. It includes individuals with mild or moderate liver problems and healthy participants matched to them. Those living with liver issues that affect daily life might be suitable for this study. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

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

Research has shown that Inaxaplin, also known as VX-147, has been tested for safety in conditions like kidney disease with high protein levels. In these studies, researchers monitored participants who took at least one dose of Inaxaplin to ensure safety. The results indicated that most participants tolerated Inaxaplin well, and no major safety issues emerged.

However, specific safety information for Inaxaplin in liver disease is not yet available. This trial is in the early stages and focuses on understanding how individuals with liver problems process the drug and whether it is safe for them. Early trials typically mark the first time a new treatment is tested in people, primarily assessing safety and how the body processes the treatment.

In summary, while Inaxaplin has generally been safe in other conditions, more information is needed to confirm its safety for liver disease. Researchers will closely monitor trial participants to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Inaxaplin is unique because it targets liver disease differently than standard treatments like antiviral medications or lifestyle changes, which primarily focus on managing symptoms or slowing disease progression. Unlike these options, Inaxaplin may act directly on liver cells to improve their function or repair damage, offering a more targeted approach. Researchers are excited about Inaxaplin because it could potentially provide faster and more effective relief for patients with varying levels of liver impairment, addressing the condition at a cellular level.

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

This trial investigates whether Inaxaplin can help treat liver disease. Participants will receive a single dose of Inaxaplin, also known as VX-147. Inaxaplin has previously shown promise in lowering high protein levels in urine for individuals with certain kidney problems by blocking a protein called APOL1, which is linked to kidney damage. This suggests potential benefits for liver issues, but more direct evidence is necessary. Early studies in other conditions offer some hope, but further research is needed to confirm its benefits for liver disease. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with mild or moderate liver disease, as well as healthy participants matched to those with liver impairment. Specific eligibility criteria are not provided.

Inclusion Criteria

I have mild liver problems (Child-Pugh score 5-6).

I am healthy and match a participant with liver issues in age, sex, and body weight.

My liver function is moderately impaired.

Exclusion Criteria

Cohorts 1 and 3: Participants with Hepatic Impairment who smoke

I am healthy but have a condition that might affect how drugs are absorbed in my body.

I have liver problems and haven't had a fever or acute illness shortly before starting the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Inaxaplin (IXP) on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inaxaplin

Trial Overview The study focuses on understanding how the body processes Inaxaplin (IXP) in people with different levels of liver health and assessing its safety and tolerability.

How Is the Trial Designed?

Group I: Cohort 4: Matched Healthy Participants Experimental Treatment 1 Intervention

Healthy participants matched to Cohort 3 will receive a single dose of IXP on Day 1.

Group II: Cohort 3: Moderate Hepatic Impairment Experimental Treatment 1 Intervention

Participants will receive a single dose of IXP on Day 1.

Group III: Cohort 2: Matched Healthy Participants Experimental Treatment 1 Intervention

Healthy participants matched to Cohort 1 will receive a single dose of IXP on Day 1.

Group IV: Cohort 1: Mild Hepatic Impairment Experimental Treatment 1 Intervention

Participants will receive a single dose of IXP on Day 1.

Who Is Running the Clinical Trial?

Vertex Pharmaceuticals Incorporated

Lead Sponsor

Trials

267

Recruited

36,100+

Dr. David Altshuler

Vertex Pharmaceuticals Incorporated

Chief Medical Officer since 2020

MD, PhD

Dr. Reshma Kewalramani

Vertex Pharmaceuticals Incorporated

Chief Executive Officer since 2020

MD, trained in internal medicine and nephrology

Published Research Related to This Trial

In a study of 41 cirrhotic patients treated with direct oral anticoagulants (DOACs) like apixaban and rivaroxaban, the overall rates of new venous thromboembolic events (VTE) and bleeding were relatively low at 7.3% and 4.8%, respectively, suggesting potential safety in this population.

Despite 29.3% of patients receiving DOACs outside FDA recommendations, the observed rates of complications were comparable to those seen in larger trials, indicating that DOACs may be a viable option for anticoagulation in patients with advanced cirrhosis, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Use Evaluation of Direct Oral Anticoagulants (DOACs) in Patients With Advanced Cirrhosis. Jarboe, L., Dadlani, A., Bandikatla, S., et al.[2022]

Up to 9% of adverse drug reactions can harm the liver, with acetaminophen being a major cause of severe liver failure, highlighting the need for careful medication management in patients with liver disease.

While many drugs are generally considered safe for patients with liver disease, some, like methotrexate and niacin, have documented risks of hepatotoxicity, and monitoring is essential due to the lack of comprehensive evidence for many other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rational use of potentially hepatotoxic medications in patients with underlying liver disease. Lewis, JH.[2019]

In a study using a rat model of liver fibrosis, Vitamin D3 (VD3) treatment significantly improved liver function by reducing harmful enzyme levels and liver damage markers after eight weeks of therapy.

VD3 demonstrated antifibrotic effects by decreasing fibrous tissue and specific gene expressions related to fibrosis, indicating its potential as a therapeutic agent for liver fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D Ameliorates the Hepatic Oxidative Damage and Fibrotic Effect Caused by Thioacetamide in Rats. Megahed, A., Gadalla, H., Abdelhamid, FM., et al.[2023]

In a study of 80 chronic hepatitis C patients treated with direct-acting antivirals, liver stiffness and inflammation significantly decreased after treatment, indicating improved liver health.

Despite the successful treatment, vitamin D levels did not improve, with over 80% of patients remaining vitamin D insufficient or deficient, suggesting that additional vitamin D supplementation may be necessary for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in hepatic fibrosis and vitamin D levels after viral hepatitis C eradication using direct-acting antiviral therapy. Sriphoosanaphan, S., Thanapirom, K., Suksawatamnuay, S., et al.[2022]

The study identified 25 cases of drug-induced liver injury (DILI) associated with Dictamni Cortex (BXP) Preparations, with 74 additional cases reported for adverse reactions, highlighting a significant concern for liver safety in patients using these herbal treatments.

Many DILI cases were linked to unreasonable medication practices, such as polypharmacy and overdosing, particularly in patients with immune diseases like psoriasis and vitiligo, suggesting a need for better risk management and understanding of individual susceptibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of epidemiological characteristics of drug induced liver injury associated with Baixianpi Preparations]. Ge, FL., Niu, M., Han, ZX., et al.[2019]

A novel approach combining pharmacoepidemiology and in silico modeling identified 18 drugs linked to immune-mediated drug-induced liver injury (IMDILI), with a high statistical significance (P < 0.00015).

The study developed a pharmacophore model with 75% sensitivity and 85% specificity to predict IMDILI, suggesting that interactions with the major histocompatibility complex and Toll-like receptors, particularly TLR-7, may play critical roles in the immune response leading to liver injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationships Between Pharmacovigilance, Molecular, Structural, and Pathway Data: Revealing Mechanisms for Immune-Mediated Drug-Induced Liver Injury. Ho, SS., McLachlan, AJ., Chen, TF., et al.[2018]

In a study of 38 elderly patients with drug-induced liver injury (DILI), approximately 32.3% of DILI-drug pairs were deemed 'avoidable' using the Liverpool adverse drug reactions avoidability tool (LAAT), indicating potential for prevention strategies.

The findings suggest that a significant portion of DILI cases in this population could be prevented, highlighting the importance of using tools like LAAT for improving patient safety and reducing healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score. Danjuma, MI., Almasri, H., Alshokri, S., et al.[2020]

Liver cirrhosis can lead to osteoporosis due to various factors, including changes in calcium and vitamin D levels, as well as nutritional issues.

Dual-energy X-ray absorptiometry (DXA) is the preferred method for measuring bone mineral density in these patients, and treatment options include calcium and vitamin D supplements, bisphosphonates, and hormonal replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osteoporosis in liver cirrhosis--overview. Cijevschi, C., Mihai, C., Drug, VL., et al.[2013]

In a study of 2,462 Korean patients, tacrolimus was associated with higher maximum levels of liver enzymes (ALT) and bilirubin compared to cyclosporine, indicating a potential risk for liver toxicity, especially in patients with preexisting liver conditions.

Patients with a history of liver disease experienced significantly greater liver damage from tacrolimus, suggesting that careful monitoring and possibly switching to cyclosporine could mitigate this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus therapy causes hepatotoxicity in patients with a history of liver disease. Ko, MS., Choi, YH., Jung, SH., et al.[2016]

Liver transplantation has shown a one-year patient survival rate of 74.7% in a study of 162 patients, indicating its effectiveness as a treatment for severe liver diseases.

Improvements in patient outcomes have been attributed to a conservative approach to immunosuppression, careful management of nutrition, and proactive treatment of complications, even as the program has accepted higher-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver transplantation at the University of Michigan. Turcotte, JG., Merion, RM., Burtch, GD., et al.[2021]

In a study of 80 patients with liver cirrhosis and chronic portal vein thrombosis, direct-acting oral anticoagulants (DOACs) showed a significant improvement in recanalization rates after 6 months of treatment, with a 28.2% rate compared to the control group.

DOACs were found to be safe, with no significant increase in bleeding risk compared to the control group, and they also improved liver function indicators like total bilirubin levels and Child-Pugh scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety study of direct-acting oral anticoagulants for the treatment of chronic portal vein thrombosis in patients with liver cirrhosis. Ai, MH., Dong, WG., Tan, XP., et al.[2021]

Clinicians managing medications for patients with liver disease should consider how liver function affects drug metabolism, including factors like first-pass metabolism, protein binding, and clearance.

The study introduces six key questions that can help healthcare providers make informed decisions about medication management in patients with liver disease, ensuring safer and more effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to manage medications in the setting of liver disease with the application of six questions. Nguyen, HM., Cutie, AJ., Pham, DQ.[2022]

In a study involving 64 liver transplant recipients, a clinical pharmacist identified 98 medication-related problems (MRPs) and proposed 113 interventions, highlighting the importance of medication management in this population.

After one year, 79% of patients with initial compliance issues improved, and 93% of patients resolved their drug indication problems, demonstrating the effectiveness of pharmacist-led interventions in enhancing medication adherence and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication-Related Problems in Liver Transplant Recipients in the Outpatient Setting: A Dutch Cohort Study. Mulder, MB., Borgsteede, SD., Darwish Murad, S., et al.[2021]

A literature review of studies from 1981 to 2017 indicates that the use of vitamin K to correct coagulopathy in patients with cirrhosis is not well supported by evidence.

The findings suggest that routine administration of vitamin K to improve prothrombin times in cirrhosis should be avoided until more definitive studies demonstrate its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine Use of Vitamin K in the Treatment of Cirrhosis-Related Coagulopathy: Is it A-O-K? Maybe Not, We Say. Aldrich, SM., Regal, RE.[2020]

Citations

1. withpower.com withpower.com/trial/phase-1-hepatic-impairment-7-2024-01003

Inaxaplin for Liver Disease · Info for Participants The available research does not provide specific data on the effectiveness of Inaxaplin for Liver Disease. Instead, it discusses the safe use of medications in ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2202396

Inaxaplin for Proteinuric Kidney Disease in Persons with ... Targeted inhibition of APOL1 channel function with inaxaplin reduced proteinuria in participants with two APOL1 variants and focal segmental glomerulosclerosis.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11696124/

Small molecule APOL1 inhibitors as a precision medicine ... They both prevent proteinuria in an acute mouse model of AMKD and resolve established proteinuria and glomerular histopathology in a chronic ...

4. investors.vrtx.com investors.vrtx.com/news-releases/news-release-details/vertex-advances-inaxaplin-vx-147-phase-3-portion-adaptive-phase

Vertex Advances Inaxaplin (VX-147) into Phase 3 Portion ... Previously reported Phase 2a proof-of-concept data demonstrated that inaxaplin led to a statistically significant and clinically meaningful mean ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/62/NCT04340362/Prot_000.pdf

Protocol VX19-147-101, Version 2.0 Page 2 of 62 Vertex ... These nonclinical data suggest that VX-147 has the potential to reduce proteinuria and reverse APOL1-induced podocyte lesions in patients with APOL1-mediated ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06529796

Evaluation of the Pharmacokinetics and Safety of Inaxaplin ... The purpose of this study is to evaluate the pharmacokinetics, safety and tolerability of Inaxaplin (IXP) in participants with mild or moderate hepatic ...

7. karger.com karger.com/gdz/article/4/1/64/896777/Safety-and-Tolerability-of-the-APOL1-Inhibitor

Safety and Tolerability of the APOL1 Inhibitor, Inaxaplin ... Based on the mechanism of disease, targeted inhibition of APOL1 should inhibit glomerular damage, reduce proteinuria, and ultimately slow the ...

8. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2021-004762-35/PT

Clinical Trials Register The European Union Clinical Trials Register allows you to search for protocol and results information on EU/EEA interventional clinical trials.