What side effects are associated with this type of intervention?

Common treatments for itching that modulate receptors or pathways involved in pruritus include selective serotonin re-uptake inhibitors (SSRIs) like paroxetine and fluvoxamine, which can cause side effects such as nausea, headache, and sleep disturbances. Leukotriene receptor antagonists like montelukast have been associated with side effects including headache, gastrointestinal issues, and potential neuropsychiatric events. Systemic treatments like dupilumab, an IL-4 receptor antagonist, can cause injection site reactions, conjunctivitis, and nasopharyngitis. These treatments aim to alleviate itching by targeting specific pathways involved in the sensation of pruritus.

What prior FDA approvals exist?

The FDA has approved several treatments for itching that modulate receptors or pathways involved in pruritus. Antihistamines such as cetirizine and levocetirizine are commonly used to block histamine receptors and reduce itching. More recently, biologics like dupilumab, which targets the IL-4 and IL-13 pathways, have been approved for conditions like atopic dermatitis that involve severe itching. Additionally, JAK inhibitors like ruxolitinib, which modulate the JAK-STAT pathway, have shown promise in reducing pruritus in clinical trials. These treatments reflect a growing understanding of the molecular mechanisms underlying itch and offer targeted approaches to managing this symptom.

What other types of research exist?

Promising novel alternatives to EP547 for treating pruritus in 2024 include: 1) Nemolizumab, an anti-IL-31 receptor A monoclonal antibody, which has shown efficacy in reducing pruritus in atopic dermatitis. 2) Dupilumab, an IL-4 receptor alpha antagonist, which is effective in treating pruritus associated with atopic dermatitis. 3) Fezakinumab, an IL-22 monoclonal antibody, which has demonstrated potential in managing pruritus in atopic dermatitis. These treatments target specific pathways involved in pruritus and have shown promising results in clinical trials.

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EP547 for Cholestatic Pruritus (PACIFIC Trial)

Q: What is the mechanism of action of this treatment?

Common treatments for itching often target specific receptors or pathways involved in the sensation of pruritus. For instance, topical capsaicin works by desensitizing sensory neurons through the depletion of substance P, a neuropeptide associated with pain and itching. Antihistamines block histamine receptors, reducing the histamine-mediated itch response. Other treatments, like those being studied in the EP547 trial, aim to modulate specific receptors or pathways directly involved in pruritus, such as bile acid receptors in cholestatic pruritus. These mechanisms are crucial for patients because they address the underlying causes of itching, providing more effective and targeted relief compared to general symptomatic treatments.

Phase 2

Waitlist Available

Research Sponsored by Escient Pharmaceuticals, Inc

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Documented primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC)

Age 18 to 80 years

Must not have

Alternative causes of liver disease

Presence of documented secondary sclerosing cholangitis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up measured from day 1 to week 6

Summary

This trial is testing a new drug called EP547 to help people with severe itching caused by specific liver diseases. The drug works by blocking the signals that make people feel itchy.

Who is the study for?

Adults aged 18-80 with moderate to severe itching due to Primary Biliary Cholangitis (PBC) or Primary Sclerosing Cholangitis (PSC) can join. They must not have cirrhosis, significant bowel issues, high-grade bile duct strictures, biliary stents, other liver diseases, or plans for a liver transplant.

What is being tested?

The trial is testing EP547 against a placebo in patients with cholestatic pruritus from PBC or PSC. It aims to see if EP547 can relieve itching better than a non-active treatment.

What are the potential side effects?

Possible side effects of EP547 are not detailed here but may include reactions similar to other medications for liver conditions and itching such as digestive discomfort, skin reactions, and changes in blood tests related to the liver.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with PBC or PSC.

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I am between 18 and 80 years old.

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I often have moderate to severe itching.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a liver condition not caused by alcohol or viruses.

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I have been diagnosed with secondary sclerosing cholangitis.

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I have itching not caused by primary biliary cholangitis or sclerosing cholangitis.

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I have cirrhosis but my liver is still working.

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I have had a major surgery on my small intestine.

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I have had or am planning to have a liver transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ measured from day 1 to week 6

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~measured from day 1 to week 6

This trial's timeline: 3 weeks for screening, Varies for treatment, and measured from day 1 to week 6 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Worst Itch Numeric Rating Scale (WI-NRS)

Secondary study objectives

Change in 5-D Itch Scale

Maximum Plasma Concentration [Cmax]

Proportion of subjects with WI-NRS <4

+6 more

Side effects data

From 2021 Phase 1 trial • 89 Patients • NCT04510090

17%

Application site irritation

17%

Erythema

17%

Application site dermatitis

100%

80%

60%

40%

20%

Study treatment Arm

SAD-HS EP547 225 mg

MAD-HS EP547 225 mg

FE-HS EP547 75 mg

SAD-HS EP547 450 mg

SAD-HS EP547 675 mg

SD-UP EP547 75 mg

SAD-HS EP547 25 mg

MAD-HS EP547 25 mg

MD-CP EP547 30 mg

SAD-HS EP547 75 mg

MAD-HS EP547 75 mg

SD-CP EP547 75 mg

SAD-HS Placebo

MAD-HS Placebo

MD-CP Placebo

MD-UP Placebo

MD-UP EP547 20 mg

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: EP547 100 mgExperimental Treatment1 Intervention

Group II: PlaceboPlacebo Group1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

EP547

2020

Completed Phase 2

~160

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for itching often target specific receptors or pathways involved in the sensation of pruritus. For instance, topical capsaicin works by desensitizing sensory neurons through the depletion of substance P, a neuropeptide associated with pain and itching. Antihistamines block histamine receptors, reducing the histamine-mediated itch response. Other treatments, like those being studied in the EP547 trial, aim to modulate specific receptors or pathways directly involved in pruritus, such as bile acid receptors in cholestatic pruritus. These mechanisms are crucial for patients because they address the underlying causes of itching, providing more effective and targeted relief compared to general symptomatic treatments.