What is the mechanism of action of this treatment?

Kappa opioid receptor agonists, such as difelikefalin, work by binding to kappa opioid receptors in the nervous system, which helps to modulate the sensation of itch and reduce its intensity. This is particularly important for patients with chronic pruritus, as traditional antihistamines often fail to provide relief for severe itching. Other treatments, such as bile acid sequestrants and opioid antagonists, work by addressing underlying causes of itching, such as cholestasis, by reducing bile acids or blocking opioid receptors that can exacerbate itch. These mechanisms are crucial for providing targeted relief and improving the quality of life for patients with persistent and severe itching.

What side effects are associated with this type of intervention?

Common treatments for itching, particularly those involving opioid antagonists like naltrexone, can cause side effects such as nausea, headache, dizziness, and fatigue. In some cases, opioid antagonists may lead to withdrawal-like symptoms. For treatments like Difelikefalin, which is a Kappa Opioid Receptor Agonist, side effects observed in clinical trials include gastrointestinal issues, dizziness, and somnolence. Other treatments for pruritus, such as antihistamines, can cause drowsiness and dry mouth, while bile acid sequestrants may lead to gastrointestinal discomfort.

What prior FDA approvals exist?

FDA-approved treatments for itching include various classes of drugs such as antihistamines, corticosteroids, and selective serotonin reuptake inhibitors (SSRIs). Notably, opioid antagonists like naltrexone have been used for cholestatic pruritus. Difelikefalin, a kappa opioid receptor agonist, represents a novel approach by targeting specific opioid receptors to alleviate pruritus. This mechanism is distinct from traditional treatments, offering a new therapeutic pathway for managing moderate to severe itching, particularly in conditions like atopic dermatitis.

What other types of research exist?

Promising, novel alternatives to Difelikefalin for treating itching in 2024 include Sertraline, Paroxetine, Tacrolimus ointment, Ruxolitinib cream, and Dupilumab.

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Difelikefalin + Topical Corticosteroid for Eczema (KIND-1 Trial)

Phase 3

Waitlist Available

Research Sponsored by Cara Therapeutics, Inc.

Eligibility Criteria Checklist

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

Must have

Subject has chronic pruritus related to AD;

Subject has moderate to severe pruritus;

Must not have

Subject has clinically infected AD

Subject has pruritus attributed to a cause other than AD

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

All Individual Drugs Already Approved

Pivotal Trial

Summary

This trial is testing a pill called difelikefalin to see if it can help reduce severe itching in adults with eczema. The pill is taken along with a common eczema cream. Difelikefalin works by blocking the signals that cause itching.

Who is the study for?

Adults with moderate to severe itching due to atopic dermatitis (AD) can join this study. They must not be pregnant or nursing and should have a confirmed diagnosis of active AD without clinical infection. Participants shouldn't have any other medical conditions that could risk their safety or affect the study's results.

What is being tested?

The trial is testing oral difelikefalin in two doses (0.25 mg and 0.5 mg) as an add-on treatment alongside a topical corticosteroid cream for adults with itchy skin from AD. It's randomized and double-blind, meaning participants are assigned treatments by chance and neither they nor the researchers know who gets what.

What are the potential side effects?

Possible side effects of difelikefalin may include nausea, dizziness, dry mouth, headache, constipation, vomiting, and sleepiness. The severity of these side effects can vary among individuals.

Eligibility Criteria

Inclusion Criteria

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

Select...

I have long-term itching due to atopic dermatitis.

Select...

I experience moderate to severe itching.

Select...

I am not pregnant or breastfeeding.

Select...

I have been diagnosed with active Alzheimer's disease.

Select...

I am not pregnant or breastfeeding.

Select...

I have moderate to severe itching.

Select...

I have been diagnosed with active Alzheimer's disease.

Select...

I have long-term itching due to atopic dermatitis.

Exclusion Criteria

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

Select...

I have a skin infection due to atopic dermatitis.

Select...

My itching is not caused by atopic dermatitis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Difelikefalin 0.5 mg tablets plus TCS creamExperimental Treatment2 Interventions

Oral difelikefalin tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed.

Group II: Difelikefalin 0.25 mg tablets plus TCS creamExperimental Treatment2 Interventions

Oral difelikefalin tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed.

Group III: Placebo tablets plus TCS creamActive Control2 Interventions

Oral placebo tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed

Group IV: Placebo tablets plus Vehicle cream (Part A only)Placebo Group2 Interventions

Oral placebo tablets administered twice daily. Vehicle cream applied by study subjects to skin lesions once a day until control is achieved, then as needed

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Difelikefalin

FDA approved

Difelikefalin

FDA approved

TCS Cream

2015

Completed Phase 2

~220

0 / 10Eligibility 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

Kappa opioid receptor agonists, such as difelikefalin, work by binding to kappa opioid receptors in the nervous system, which helps to modulate the sensation of itch and reduce its intensity. This is particularly important for patients with chronic pruritus, as traditional antihistamines often fail to provide relief for severe itching. Other treatments, such as bile acid sequestrants and opioid antagonists, work by addressing underlying causes of itching, such as cholestasis, by reducing bile acids or blocking opioid receptors that can exacerbate itch. These mechanisms are crucial for providing targeted relief and improving the quality of life for patients with persistent and severe itching.

Efficacy and Safety of Difelikefalin in Japanese Patients With Moderate to Severe Pruritus Receiving Hemodialysis: A Randomized Clinical Trial.Post-marketing surveillance study of the safety and efficacy of nalfurafine hydrochloride (Remitch® capsules 2.5 μg) in 3,762 hemodialysis patients with intractable pruritus.