Topical KB105 for the Treatment of TGM1-deficient Autosomal Recessive Congenital Ichthyosis (ARCI)

Study Overview
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Brief Summary
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KB105-02 is an intrasubject randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of KB105 in children and adults with autosomal recessive congenital ichthyosis (ARCI).

Official Title
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A Phase 2, Randomized, Placebo-controlled Study of Topical KB105, a Replication-defective, Non-integrating HSV-1 Vector Expressing Human Transglutaminase 1 (TGM1) for the Treatment of TGM1-deficient Autosomal Recessive Congenital Ichthyosis (ARCI)

Conditions
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Autosomal Recessive Ichthyosis

Intervention / Treatment
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* Biological: KB105
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subject, or legally authorized representative, must be willing and able to give informed consent/assent Aged ≥6 months A genetically confirmed diagnosis of TGM1-deficient ARCI Clinical diagnosis of lamellar ichthyosis Two target areas located on similar anatomical regions with the same scaling severity by IGA and scaling severity ≥3 Subjects taking systemic retinoids must be on a stable regimen for at least 4 weeks and agree to continue to take the medication consistently throughout the study. If the subject prefers to withhold systemic retinoids during the study, then a minimum 4-week washout period is required Clinically stable and in good general health Key Exclusion Criteria: Subject has a physical condition or other dermatological disorder (e.g., atopic, seborrheic, or contact dermatitis, psoriasis, tinea infections, etc.) which, in the Investigator's opinion, might impair evaluation of the target areas or which exposes the subject to unacceptable risk by study participation Participation in another clinical study or treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer Any condition or illness (including a history or current evidence of substance abuse or dependence) that, in the opinion of the Investigator, would impact a subject's ability to complete all study-related procedures and/or poses an additional risk to the assessment of safety of KB105 Women who are pregnant or nursing Subject who is unwilling to comply with contraception requirements per protocol Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol in the opinion of the Investigator

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An intra-participant parallel study. Matched target areas will be randomized within the participant, such that one target area receives KB105 and the other target area will receive placebo. An additional target area may be selected to receive open-label treatment with KB105.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KB105<br>Weekly topical application | Biological: KB105<br>* Replication-defective, non-integrating HSV-1 vector expressing TGM1 formulated as a topical gel<br>|
| Placebo Comparator: Placebo<br>Weekly topical application | Other: Placebo<br>* Visually matched excipient gel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Investigator's Global Assessment (IGA) Responder (Comparison of proportion of responder KB105 target areas to responder placebo target areas) | Responder target areas are defined as: Target areas with ≥2 point reduction from baseline on IGA scaling severity at Week 9 or Target areas with ≥1 point reduction from baseline on IGA scaling severity for 2 consecutive weeks (Week 8 and Week 9) | Week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite regional Visual Index of Ichthyosis Severity (VIIS) responder (Comparison of proportion of responder KB105 target areas to responder placebo target areas) | Responder target areas are defined as: Target areas with ≥2 point reduction from baseline on VIIS scaling score at Week 9 or Target areas with ≥1 point reduction from baseline on VIIS scaling score for 2 consecutive weeks (Week 8 and Week 9) | Week 9 | 
| Visual Index of Ichthyosis Severity score change from baseline | Change from baseline in regional Visual Index of Ichthyosis Severity (VIIS) scaling scores, where 0 is normal and 4 is severe | Up to 11 weeks | 
| Investigator's Global Assessment change from baseline | Change from baseline in Investigator's Global Assessment (IGA) scaling severity scores, where 0 is clear and 4 is severe | Up to 11 weeks | 
| Investigator's Global Assessment (IGA) 2 point responder | Comparison of proportion of KB105 and placebo target areas with ≥2 point reduction from baseline on IGA scaling severity at Week 9 | Week 9 | 
| Investigator's Global Assessment (IGA) 1 point responder | Comparison of proportion of KB105 and placebo target areas with ≥1 point reduction from baseline on IGA scaling severity for 2 consecutive weeks (Week 8 and Week 9) | Week 9 | 
| Visual Index of Ichthyosis Severity (VIIS) 2 point responder | Comparison of proportion of KB105 and placebo target areas with ≥2 point reduction from baseline on regional VIIS scaling severity at Week 9 | Week 9 | 
| Visual Index of Ichthyosis Severity (VIIS) 2 point responder | Comparison of proportion of KB105 and placebo target areas with ≥1 point reduction from baseline on regional VIIS scaling severity for 2 consecutive weeks (Week 8 and Week 9) | Week 9 |