Mirdametinib for Liver Disease

Recruiting at 1 trial location

Overseen By SpringWorks Clinical

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: SpringWorks Therapeutics, Inc.

Must not be taking: P-glycoprotein inhibitors

Disqualifiers: HIV, Cancer, GI surgery, others

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

Compensation: Varies

Number of Visits: 34

Duration: 8 days

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how the body processes and reacts to a new drug called Mirdametinib, particularly in individuals with moderate or severe liver problems. Researchers seek to understand how the drug is absorbed, broken down, and eliminated by the body, as well as to identify any side effects it may cause. The study includes participants with liver issues and healthy volunteers to compare differences in drug processing. Ideal candidates for this trial are those with long-term, stable liver conditions or healthy individuals without liver disease who are willing to refrain from alcohol during the study. As a Phase 1 trial, this research focuses on understanding how Mirdametinib works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that your current medications be stable for at least 28 days before starting the study treatment. However, if your medications are fluctuating, you might still be eligible on a case-by-case basis with approval from the Sponsor.

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

Research shows that mirdametinib has been tested in people with mild liver problems, and it did not significantly affect how the body processes the drug. However, its effects on individuals with moderate or severe liver issues remain unknown.

Previous studies have identified some side effects of mirdametinib, including liver damage, speech difficulties, and movement problems like tremors or symptoms similar to Parkinson's disease. Prospective participants should consider these potential reactions when deciding to join a study involving this drug.

As this trial is in an early stage, the main goal is to assess how well people tolerate the drug and identify any side effects. Consequently, limited safety information is available, particularly for those with more serious liver conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Mirdametinib is unique because it targets the MEK1/2 pathway, which is a different approach compared to current treatments for liver disease that typically focus on controlling symptoms and managing complications. Researchers are excited about Mirdametinib as it offers a targeted therapy that directly interferes with cell signaling pathways involved in liver disease progression. This specificity could potentially lead to more effective management of liver conditions with fewer side effects.

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

Research has shown that Mirdametinib has potential in treating various conditions, but limited data exists on its effects on liver disease. In other studies, about 41% of adults responded well to Mirdametinib, suggesting its effectiveness. This trial will evaluate Mirdametinib in participants with varying levels of hepatic impairment, including severe and moderate, as well as healthy matched participants. The drug works by blocking a pathway in cells that can worsen diseases, which is why researchers are testing it for liver conditions. Although specific information on liver disease is limited, its mechanism and positive results in other conditions suggest potential benefits. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with moderate or severe liver impairment, as well as healthy volunteers to serve as a comparison group. Participants must be able to swallow pills and not have other significant medical conditions that could interfere with the study.

Inclusion Criteria

I have long-term, stable liver problems but am in good health otherwise.

I have good vein access in at least one arm for blood tests.

I am not pregnant, using birth control, and agree to pregnancy tests.

Exclusion Criteria

I have had a serious infection recently.

Participant is deemed unsuitable for the study by the Investigator for any additional reason, condition, or prior therapy

I don't have recent major surgeries, chronic bowel issues, recent cancer, severe acute illness, known allergies to study drugs, recent heavy alcohol use, or recent large blood donations. I'm willing to avoid certain activities and don't take excluded medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive mirdametinib to assess pharmacokinetics and tolerability

8 days

Multiple visits including D-1, D1, and D8/ET

Follow-up

Participants are monitored for safety and effectiveness after treatment

32 days

Assessments up to 32 days post-dose

What Are the Treatments Tested in This Trial?

Interventions

• Mirdametinib

Trial Overview The study is testing Mirdametinib, a MEK inhibitor drug, by comparing how individuals with different levels of liver function process it. It will look at the amount of drug in the blood over time and its breakdown products.

How Is the Trial Designed?

Group I: Severe Hepatic Impairment Experimental Treatment 1 Intervention

Group II: Moderate Hepatic Impairment Experimental Treatment 1 Intervention

Group III: Healthy Match Participants Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

SpringWorks Therapeutics, Inc.

Lead Sponsor

Trials

14

Recruited

900+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06997276

NCT06997276 | Effect of Hepatic Impairment on the ... How well the study drug is tolerated and any side effects that may occur in participants with moderate or severe liver function impairment compared to ...

2. withpower.com withpower.com/trial/mirdametinib-for-liver-disease-c2968

Mirdametinib for Liver Disease This Phase 1 medical study run by SpringWorks Therapeutics, Inc. is evaluating whether Mirdametinib will have tolerable side effects & efficacy for patients ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11825507/

ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and ... Twenty-four adults (41%; 95% CI, 29 to 55) achieved a confirmed objective response by BICR during the treatment phase, which was significantly ...

4. targetedonc.com targetedonc.com/view/study-reveals-mirdametinib-as-potential-game-changer-in-nf1-associated-pns

Study Reveals Mirdametinib as Potential Game-Changer in ... Here, mirdametinib demonstrated a high overall response rate (ORR) with 41% (95% CI, 29%-55%; P <.001 vs null) of adult patients and 52% (95% CI ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03962543

NCT03962543 | MEK Inhibitor Mirdametinib (PD-0325901) ... Participant has abnormal liver function or history of liver disease. Participant has lymphoma, leukemia or any malignancy within the past 5 years (except for ...

6. ema.europa.eu ema.europa.eu/en/documents/product-information/ezmekly-epar-product-information_en.pdf

Ezmekly, INN-mirdametinib - European Medicines Agency Population pharmacokinetic analyses in patients with mild hepatic impairment indicate no meaningful effects on exposure. Paediatric population.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/219379Orig1s000,219389Orig1s000MultidisciplineR.pdf

219379Orig1s000 219389Orig1s000 - accessdata.fda.gov Hepatic Impairment: The effects of hepatic impairment on the PK of mirdametinib have not ... The pivotal safety data supporting the safety evaluation of ...

8. drugs.com drugs.com/dosage/mirdametinib.html

Mirdametinib Dosage Guide + Max Dose, Adjustments Mild Liver Dysfunction (total bilirubin less or equal to upper limit ... Safety and efficacy have not been established in patients younger than 2 ...

9. medlink.com medlink.com/articles/mirdametinib

Mirdametinib The effects of moderate or severe hepatic impairment, severe renal impairment ... liver damage, dysarthria, dystonia, tremor, parkinsonism ...