Difelikefalin + Topical Corticosteroid for Eczema

(KIND-1 Trial)

No longer recruiting at 64 trial locations

Overseen By Cara Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cara Therapeutics, Inc.

Must be taking: Topical corticosteroids

Disqualifiers: Infected AD, Non-AD pruritus, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of an oral medication, difelikefalin, and a topical corticosteroid cream to evaluate its effectiveness in reducing itching in people with moderate to severe eczema (also known as atopic dermatitis). Participants will receive one of two doses of difelikefalin or a placebo, all alongside a corticosteroid cream. The study aims to determine if adding difelikefalin to the usual cream treatment can better manage itching. Suitable candidates for this trial have been diagnosed with active eczema and experience frequent, severe itching due to their condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for eczema.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that difelikefalin is generally well-tolerated by most patients. One study found it helped reduce itchy skin and was safe for adults with eczema-related itchiness. Most side effects, such as nausea or dizziness, were mild and short-lived.

Difelikefalin also has FDA approval to treat itchiness in adults with kidney problems, indicating a known safety record for use in people. While every treatment can have side effects, evidence so far shows difelikefalin is safe to use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about difelikefalin for eczema because it offers a new way to tackle symptoms. Unlike standard treatments like topical corticosteroids alone, which mainly reduce inflammation, difelikefalin works by targeting specific receptors in the nervous system to potentially ease itching. This dual approach—combining oral difelikefalin with topical corticosteroids—could provide more comprehensive relief, addressing both inflammation and itchiness. Additionally, difelikefalin is taken orally, which could offer convenience and improve adherence compared to solely topical treatments.

What evidence suggests that this trial's treatments could be effective for atopic dermatitis?

Research has shown that oral difelikefalin can help reduce itching in people with moderate to severe atopic dermatitis, a condition that causes itchy and inflamed skin. Earlier studies found that patients who took difelikefalin experienced less itching, particularly those primarily affected by itching. Difelikefalin also lowered levels of substances in the body linked to itching and inflammation. In this trial, participants will receive either difelikefalin at different dosages or a placebo, all in combination with topical corticosteroid (TCS) cream. Although previous studies suggested that using difelikefalin with TCS creams did not always provide extra benefits compared to the cream alone, this trial aims to further explore the potential added benefits of difelikefalin when used with TCS cream. ^{2 4 6 7 8}

Who Is on the Research Team?

Cara Therapeutics

Principal Investigator

Cara Therapeutics

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I am not pregnant or breastfeeding.

I experience moderate to severe itching.

I have long-term itching due to atopic dermatitis.

Exclusion Criteria

I have a skin infection due to atopic dermatitis.

My itching is not caused by atopic dermatitis.

Subject has any clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive oral difelikefalin or placebo tablets BID plus TCS cream for 12 weeks

12 weeks

Open-label Extension

Participants may continue treatment with oral difelikefalin plus TCS cream for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Difelikefalin
• Topical Corticosteroid Cream

Trial Overview 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.

How Is the Trial Designed?

Group I: Difelikefalin 0.5 mg tablets plus TCS cream Experimental Treatment 2 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 cream Experimental Treatment 2 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 cream Active Control 2 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 Group 2 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

Who Is Running the Clinical Trial?

Cara Therapeutics, Inc.

Lead Sponsor

Trials

24

Recruited

5,100+

Published Research Related to This Trial

Topical corticosteroids (TCS) used for atopic eczema showed no significant increased risk of skin thinning in short-term studies, indicating they are generally safe for use in both adults and children.

While TCS may have a higher relative risk of skin thinning compared to topical calcineurin inhibitors, the overall long-term safety data is limited, suggesting that intermittent use of TCS is safe but requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of topical corticosteroids in atopic eczema: an umbrella review. Axon, E., Chalmers, JR., Santer, M., et al.[2023]

Doxepin 5% cream has been approved for relieving itching associated with eczema in adults and children over 12, providing a new treatment option beyond traditional methods like emollients and corticosteroids.

The review assesses both the efficacy and safety of doxepin cream, highlighting its potential role in managing eczema-related pruritus effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxepin cream for eczema? [2019]

In a pilot study involving Italian adults with eczema, the new non-steroid anti-inflammatory cream showed effectiveness in reducing eczema severity, with recovery rates of 58.3% in the non-steroid group compared to 91.7% in the Hydrocortisone group when following the treatment protocol closely.

While Hydrocortisone Butyrate 0.1% Cream was more effective overall, the non-steroid cream demonstrated significant clinical improvement at each assessment point, suggesting it could be a viable long-term treatment option for eczema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non steroid treatment for eczema: results from a controlled and randomized study. De Waure, C., Cadeddu, C., Venditti, A., et al.[2015]

In a 3-week study involving 301 patients with eczematous dermatoses, once-daily applications of 0.05% diflorasone diacetate cream or ointment showed significant efficacy, with over 80% of patients rating their treatment as good or excellent.

The treatment was generally well-tolerated, with only 16 patients experiencing mild side effects like transient burning and stinging, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of once-daily applications of diflorasone diacetate in eczematous dermatoses. Squires, DJ., Masson, EL.[2017]

Citations

1. jacionline.org jacionline.org/article/S0091-6749(23)00888-6/fulltext

Oral difelikefalin reduces moderate to severe pruritus and ... Oral difelikefalin reduces moderate to severe pruritus and expression of pruritic and inflammatory biomarkers in subjects with atopic dermatitis.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05387707

NCT05387707 | Study to Evaluate the Efficacy and Safety ... In Part A of the study, oral difelikefalin as adjunct to topical corticosteroids (TCS) did not demonstrate meaningful clinical benefit compared to TCS alone.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0091674923008886

Oral difelikefalin reduces moderate to severe pruritus and ... DFK treatment reduced itch in subjects with moderate to severe AD-related pruritus, particularly those with an “itch-dominant” AD phenotype.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37453614/

Oral difelikefalin reduces moderate to severe pruritus and ... DFK treatment reduced itch in subjects with moderate to severe AD-related pruritus, particularly those with an "itch-dominant" AD phenotype.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04018027

Study to Evaluate the Efficacy and Safety of Oral ... This is a multicenter, randomized, double-blind, 4-arm, placebo-controlled study to evaluate the efficacy and safety of twice-daily (BID) oral difelikefalin ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04018027

NCT04018027 | Study to Evaluate the Efficacy and Safety ... This is a multicenter, randomized, double-blind, 4-arm, placebo-controlled study to evaluate the efficacy and safety of twice-daily (BID) oral difelikefalin ( ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK612386/

Difelikefalin - LiverTox - NCBI Bookshelf - NIH Difelikefalin is a synthetic tetrapeptide agonist of the kappa opioid receptor that is used to treat pruritus in adults with chronic kidney ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2210699

Phase 2 Trial of Difelikefalin in Notalgia Paresthetica We evaluated the efficacy and safety of oral difelikefalin for the treatment of moderate-to-severe pruritus associated with notalgia paresthetica.