A Vehicle Controlled Study to Evaluate Safety and Efficacy of Topical TMB-001 for Treatment of Congenital Ichthyosis
- Registration Number
- NCT04154293
- Lead Sponsor
- Timber Pharmaceuticals Inc.
- Brief Summary
The purpose of this study is to investigate the efficacy and safety of two concentrations of topically applied ointment formulation of isotretinoin called TMB-001 (0.05% and 0.1% isotretinoin) in subjects 9 years of age and older for the treatment of congenital ichthyosis (CI), including recessive X-linked ichthyosis (RXLI) and autosomal recessive congenital ichthyosis-lamellar ichthyosis (ARCI-LI) subtypes.
Funding Source FDA-OOPD
- Detailed Description
This is a randomized, parallel, double-blind, vehicle-controlled study to evaluate the safety and efficacy of two concentrations of topical TMB-001 for the treatment of CI in subjects with either the ARCI-LI or RXLI subtypes. The duration of treatment will be 12 weeks. Each subject will participate in the study for up to 24 weeks (including up to a 90-day Screening period). Eleven study centers from United States of America and Australia participated in this global study. Each subject participated in the study for up to 24 weeks (including up to a 90-day Screening period).
Eligible subjects were randomized (1:1:1) to one of 3 treatment groups:
1. TMB-001, 0.05%, twice daily (bid)
2. TMB-001, 0.1%, bid
3. Vehicle Ointment (Control), 0%, bid
Subjects were evaluated on a monthly basis for safety and efficacy results over the 12- week treatment period. Efficacy was determined in 2 ways:
1. VIIS (or Visual Index of Ichthyosis Severity) "treatment success" (VIIS-50) was defined as ≥ 50% reduction from Baseline for VIIS scaling score for the sum of the scores for 'VIIS body areas' that had a Baseline score ≥ 3). The proportion of subjects achieving VIIS-50 at Visit 6 at Week 12 relative to Baseline was the primary efficacy endpoint and time point used to compare the two active treatments to vehicle.
2. The proportion of subjects achieving IGA (Investigator Global Assessment) treatment success will be the key secondary endpoint. For this endpoint, the IGA score was established as "treatment success" or "treatment failure" where "treatment success" is defined as at least a 2-grade decrease in severity score (for example, severe or score of 4 at baseline to mild or score of 2 at Visit 6) relative to Baseline at Visit 6 at week 12.
The safety analyses conducted were extent of exposure, changes in physical examinations and vital signs, blood and urine testing including urine pregnancy testing as indicated, local skin reactions (including burning/stinging, redness, erosions, and swelling) and other adverse events.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 34
- Subject is male or female, 9 years of age or older at Visit 2 (Baseline)
- Subject has provided written informed consent
- Females of child bearing potential must be surgically sterile or agree to 2 forms of birth control
- Subject has clinical diagnosis of Congenital Ichthyosis with genetic confirmation of subtype
- Subject has between 10% and 90% total BSA affected by Congenital Ichthyosis
- Subject has at least 2 VIIS assessment areas with a scaling score of 3 or greater
- Subject has inflammatory skin diseases unrelated to ichthyosis
- Subject has used other prohibited topical treatments in the assessment areas within certain days from baseline
- Subject has used systemic retinoids within12 weeks of baseline
- Subject has untreated secondary infections
- Subject has lesions suspicious for skin cancer or untreated skin cancers
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vehicle Ointment (Control) Vehicle Topical, BID (Twice daily) TMB-001 Ointment, 0.1% Isotretinoin Topical, BID (Twice daily) TMB-001 Ointment, 0.05% Isotretinoin Topical, BID ( twice daily)
- Primary Outcome Measures
Name Time Method Number of Subjects With Reduction in Targeted Ichthyosis Severity Using the Visual Index for Ichthyosis Severity Measurement 12 weeks Number of subjects with Visual Index for Ichthyosis Severity (VIIS) treatment success, defined as 50% or greater decreased in VIIS scaling score
- Secondary Outcome Measures
Name Time Method Number of Subjects With Reduction in Overall Ichthyosis Severity as Measured With Investigator Global Assessment 12 weeks Number of subjects with Investigator Global Assessment decrease in disease severity by at least 2 grades
Change in I-NRS (Itch-Numeric Rating Scale) From Baseline at Week 12 12 weeks Mean numeric Change from baseline in Itch-Numeric Rating Scale (I-NRS) at Week 12 for entire population. I-NRS is an 11-point visual analogue scale scored based upon 0 being no itch and 10 being worst itch imaginable. Subjects were asked to grade their itch on such a scale at each visit where I-NRS was administered. A 4-point change from baseline is considered clinically significant
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12 12 weeks Change from Baseline in Dermatology Life Quality Index (DLQI) at Week 12 in all adult subjects.
The DLQI is validated in all subjects over age 16 years and is a 10-question questionnaire which requests information on how the dermatological condition affects different aspects of their life. Each question is scored on a 0-3 scale (0=no impact, 3=major impact) for a total possible maximal score of 30. Scores over 11 in adults are considered to indicate moderate impairment of quality of life due to the skin disease. A 4-point improvement from baseline is considered clinically significant
Trial Locations
- Locations (11)
Minnesota Clinical Study Center
🇺🇸New Brighton, Minnesota, United States
Yale Center for Clinical Investigation
🇺🇸New Haven, Connecticut, United States
Austin Institute for Clinical Research, Inc
🇺🇸Metairie, Louisiana, United States
Medical Dermatology Specialists
🇺🇸Phoenix, Arizona, United States
Queensland Children's Hospital
🇦🇺Brisbane, Queensland, Australia
Murdoch Children's Research Institute, RCH
🇦🇺Melbourne, Victoria, Australia
Stanford University School of Medicine
🇺🇸Palo Alto, California, United States
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
The Indiana Clinical Trials Center
🇺🇸Plainfield, Indiana, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Premier Specialists, The church
🇦🇺Kogarah, Sydney, Australia