KT-621 for Eczema

(BroADen Trial)

Recruiting at 11 trial locations

Overseen By Kymera Medical Director

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Kymera Therapeutics, Inc.

Must not be taking: Interleukin inhibitors, JAK inhibitors

Disqualifiers: Respiratory, Cardiovascular, Substance abuse, others

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

Compensation: Varies

Number of Visits: 44

Duration: 4 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants with a history of lack of response to certain medications are excluded, which might imply some restrictions. It's best to discuss your specific medications with the trial team.

Is KT-621 safe for use in humans?

Tacrolimus ointment, which may be similar to KT-621, has been used safely for treating skin conditions like eczema, with common side effects being mild skin burning and itching. However, there is a warning about a potential increased risk of cancer with long-term use of calcineurin inhibitors like tacrolimus. ^{1 2 3 4 5}

How is the drug KT-621 different from other eczema treatments?

KT-621, also known as CKD-602, is unique because it is a camptothecin derivative, which is typically used as an anticancer agent. Its mechanism involves inhibiting topoisomerase, an enzyme important for DNA replication, which is not a common approach in eczema treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of orally administered KT-621 in adult male and female patients with moderate to severe atopic dermatitis (AD).

Eligibility Criteria

Adults aged 18-55 with moderate to severe atopic dermatitis (AD) for at least a year can join. They must have an EASI score of 16 or more, vIGA of 3+, and AD on at least 10% body area. Participants need a history of poor response or contraindication to topical AD meds and should use moisturizer regularly.

Inclusion Criteria

Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures

Weekly average Peak Pruritus Numeric Rating Scale (NRS) of at least 4 at the baseline visit

I have used a moisturizer twice daily for the last 7 days.

Exclusion Criteria

Participants who have a clinically relevant history of various diseases or disorders

Participants with a history of alcohol or substance abuse within the previous 2 years

Participants who have any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral doses of KT-621 for 28 days

4 weeks

Visits on Days 1 and 15

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Safety follow-up visit on Day 43

Treatment Details

Interventions

• KT-621

Trial Overview The trial is testing KT-621, an oral medication for adults with moderate to severe AD. It aims to assess the drug's safety, how well it's tolerated, its movement through and effect on the body, and its effectiveness in reducing symptoms.

Participant Groups

Group I: KT-621 Experimental Treatment 1 Intervention

Each participant receives daily oral doses of KT-621 throughout the 28-day treatment period.

Who Is Running the Clinical Trial?

Kymera Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

850+

Findings from Research

Tacrolimus ointment, while effective for treating various inflammatory skin diseases, including oral lichen planus, has been associated with potential risks, including an increased risk of cancer, as highlighted by a case where a patient developed squamous cell carcinoma after prolonged use.

The study suggests that tacrolimus may influence cancer signaling pathways, such as the MAPK and p53 pathways, indicating that its carcinogenic effects could extend beyond just immune suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report. Becker, JC., Houben, R., Vetter, CS., et al.[2020]

A review of 24 studies on emollients for atopic dermatitis found that while adverse events were reported, none were serious, suggesting that these treatments are generally safe for use.

The most common adverse events were mild skin reactions, with the proportion of participants experiencing treatment-related issues ranging from 2% to 59%, highlighting the need for better reporting and more comprehensive studies on emollient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events from Emollient Use in Eczema: A Restricted Review of Published Data. Bhanot, A., Huntley, A., Ridd, MJ.[2021]

Dermacare, a new cosmetic formulation for atopic dermatitis, was found to be safe and well-tolerated in a multicenter study with no reported adverse events, demonstrating its potential for daily use.

After 28 days of treatment, Dermacare significantly reduced skin barrier disruption, as shown by a 70.4% decrease in the Eczema Area and Severity Index and a 36.7% decrease in transepidermal water loss, indicating improved skin condition and quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Cosmetic Formulation for the Treatment of Mild to Moderate Infantile Atopic Dermatitis. de Lucas, R., García-Millán, C., Pérez-Davó, A., et al.[2020]

In two studies involving 631 adults with moderate to severe atopic dermatitis, tacrolimus ointment (0.03% or 0.1%) was found to be effective, significantly outperforming the vehicle in all measured efficacy parameters over 12 weeks.

While some patients experienced mild adverse events like skin burning and pruritus, these were generally brief and resolved quickly; importantly, tacrolimus ointment was deemed safe, with no significant laboratory changes and low systemic absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety. Soter, NA., Fleischer, AB., Webster, GF., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events from Emollient Use in Eczema: A Restricted Review of Published Data. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

New Cosmetic Formulation for the Treatment of Mild to Moderate Infantile Atopic Dermatitis. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety. [2022]

5. Slovenia pubmed.ncbi.nlm.nih.gov

The topical calcineurin inhibitor pimecrolimus in atopic dermatitis: a safety update. [2014]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Preformulation studies of a novel camptothecin anticancer agent, CKD-602: physicochemical characterization and hydrolytic equilibrium kinetics. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Chitosan stabilized camptothecin nanoemulsions: Development, evaluation and biodistribution in preclinical breast cancer animal mode. [2018]

8. Greece pubmed.ncbi.nlm.nih.gov

CKD-602, a camptothecin derivative, inhibits proliferation and induces apoptosis in glioma cell lines. [2013]

9. Scotland pubmed.ncbi.nlm.nih.gov

Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Structure-activity relationship of alkyl camptothecin esters. [2019]