What is the mechanism of action of this treatment?

Ichthyosis, particularly autosomal recessive congenital ichthyosis (ARCI), often results from genetic mutations that impair skin barrier function. The most common treatments aim to manage symptoms through moisturizing agents, keratolytics, and retinoids to reduce scaling and improve skin hydration. Gene therapy, such as the KB105 trial, targets the root cause by delivering a functional TGM1 gene to correct the genetic defect. This approach is significant for Ichthyosis patients as it offers the potential for a long-term solution by addressing the underlying genetic issue, rather than just alleviating symptoms.

What side effects are associated with this type of intervention?

Gene therapy for Ichthyosis, like KB105, can have side effects including immune reactions, insertional mutagenesis, and off-target effects. Other treatments such as topical retinoids may cause skin irritation, dryness, and increased sensitivity to sunlight, while systemic retinoids can lead to liver toxicity, elevated lipid levels, and teratogenic effects. Moisturizers and keratolytic agents generally have minimal side effects but can occasionally cause local irritation or allergic reactions.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved gene therapies for the treatment of Ichthyosis, including autosomal recessive congenital ichthyosis (ARCI) caused by TGM1 deficiency. Current treatments for Ichthyosis primarily focus on managing symptoms and include topical keratolytics, emollients, and retinoids. KB105 represents a novel approach by delivering a functional TGM1 gene to correct the genetic defect in ARCI, which is still under investigation.

What other types of research exist?

Promising novel alternatives to KB105 for Ichthyosis patients include: 1) Protein replacement therapy, which involves delivering recombinant collagen type VII to skin wounds, showing potential in preclinical studies. 2) Beremagene geperpavec (B-VEC), a topical gene therapy using a modified herpes simplex virus 1 vector to deliver the COL7A1 gene, has demonstrated significant wound healing in clinical trials for dystrophic epidermolysis bullosa. These therapies represent innovative approaches that could be considered for Ichthyosis treatment in 2024.

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Virus Therapy

Topical KB105 for Ichthyosis

Phase 2

Waitlist Available

Research Sponsored by Krystal Biotech, Inc.

Eligibility Criteria Checklist

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

Must have

A genetically confirmed diagnosis of TGM1-deficient ARCI

Two target areas located on similar anatomical regions with the same scaling severity by IGA and scaling severity ≥3

Must not have

Subject who is unwilling to comply with contraception requirements per protocol

Women who are pregnant or nursing

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 11 weeks

Summary

This trial is testing KB105, a new treatment for a genetic skin condition called autosomal recessive congenital ichthyosis (ARCI). The study includes both children and adults who suffer from this condition. KB105 aims to improve their skin by addressing the underlying genetic cause.

Who is the study for?

This trial is for children and adults with a clinical diagnosis of lamellar ichthyosis, specifically TGM1-deficient ARCI. Participants must be in good health, at least 6 months old, and on a stable regimen if taking systemic retinoids or agree to a washout period. They cannot join if they have other skin conditions that could affect the study or are pregnant/nursing.

What is being tested?

The trial tests KB105's safety and effectiveness against placebo in treating ARCI. It's an intrasubject randomized study where each participant receives both the treatment and placebo on different parts of their body without knowing which is which.

What are the potential side effects?

While specific side effects aren't listed here, participants will be closely monitored for any adverse reactions to KB105 compared to the placebo during the trial.

Eligibility Criteria

Inclusion Criteria

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

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I have a genetic diagnosis of TGM1-deficient ARCI.

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I have two skin areas with severe scaling of the same intensity.

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I have been diagnosed with lamellar ichthyosis.

Exclusion Criteria

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

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I am unwilling to follow the study's birth control requirements.

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I am not pregnant or nursing.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 11 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 11 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 11 weeks for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Composite Investigator's Global Assessment (IGA) Responder (Comparison of proportion of responder KB105 target areas to responder placebo target areas)

Secondary study objectives

Composite regional Visual Index of Ichthyosis Severity (VIIS) responder (Comparison of proportion of responder KB105 target areas to responder placebo target areas)

Investigator's Global Assessment (IGA) 1 point responder

Investigator's Global Assessment (IGA) 2 point responder

+3 more

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: KB105Experimental Treatment1 Intervention

Weekly topical application

Group II: PlaceboPlacebo Group1 Intervention

Weekly topical application

0 / 5Eligibility 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

Ichthyosis, particularly autosomal recessive congenital ichthyosis (ARCI), often results from genetic mutations that impair skin barrier function. The most common treatments aim to manage symptoms through moisturizing agents, keratolytics, and retinoids to reduce scaling and improve skin hydration. Gene therapy, such as the KB105 trial, targets the root cause by delivering a functional TGM1 gene to correct the genetic defect. This approach is significant for Ichthyosis patients as it offers the potential for a long-term solution by addressing the underlying genetic issue, rather than just alleviating symptoms.

Effects of thermal therapy combined with blue light-emitting diode irradiation on trimellitic anhydride-induced acute contact hypersensitivity mouse model.