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

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)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Autosomal Recessive Ichthyosis
• Intervention / Treatment: Biological: KB105; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Brittani Agostini, RN, CCRC; Phone Number: 412-586-5830; Email: bagostini@krystalbio.com

Study Locations

• United States
  • California
    • Rancho Santa Margarita, California, United States, 92688
      • Mission Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Subject, or legally authorized representative, must be willing and able to give informed consent/assent
2. Aged ≥6 months
3. A genetically confirmed diagnosis of TGM1-deficient ARCI
4. Clinical diagnosis of lamellar ichthyosis
5. Two target areas located on similar anatomical regions with the same scaling severity by IGA and scaling severity ≥3
6. 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
7. Clinically stable and in good general health

Key Exclusion Criteria:

1. 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
2. Participation in another clinical study or treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer
3. 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
4. Women who are pregnant or nursing
5. Subject who is unwilling to comply with contraception requirements per protocol
6. Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol in the opinion of the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Krystal Biotech, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: February 9, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Abnormalities; Keratosis; Ichthyosis; Ichthyosis, Lamellar; Ichthyosiform Erythroderma, Congenital
• Other Study ID Numbers: KB105-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No