Congenital ichthyosis
Conditions
Interventions
Product Name: TMB-001 ointment 0.05%
Product Code: TMB-001
Pharmaceutical Form: Ointment
Pharmaceutical form of the placebo: Ointment
Route of administration of the placebo: Cutaneous use
Sponsors
Timber Pharmaceuticals, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must fulfill all of the following inclusion criteria to be eligible for participation: 1. Subject is male or female, 6 years of age and older at Visit 2 (Baseline). 2. Subject has provided written informed consent/assent. A subject under 18 years of age must provide written informed assent and be accompanied by the parent or legal guardian at the time of consent/assent signing. The parent or legal guardian must provide informed consent for the subject. If a subject becomes 18 years of age during the study, the subject must provide written informed consent at that time to continue study participation. 3. Females must be postmenopausal (defined as amenorrhea greater than 12 consecutive months in women 50 years of age and older), surgically sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or use 2 acceptable forms of birth control. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and negative urine pregnancy test (UPT) at Visit 2 (Baseline) (UPTs must have a minimum sensitivity to detect 25 mIU beta-human chorionic gonadotropin [ß-hCG]/mL). Methods of acceptable contraception are further defined in Appendix 4. Female subjects who become sexually active or begin to have relations with a partner during the study must agree to use 2 forms of birth control for 30 days prior to having relations and to continue such forms of birth control for the duration of the study. 4. Subject has clinical diagnosis of CI based upon phenotype and has a genetic confirmation of either ARCI (including but not exclusively transglutaminase 1-deficient, ALOX-12B) or RXLI (e.g., deletion of steroid sulfatase gene) subtypes of CI. Other genetically confirmed ARCI mutations can potentially be enrolled as long as the phenotype is consistent with ARCI and the other inclusion criteria are met, as determined by the Investigator (Appendix 5). 5. The amount of CI affected skin in the Treatment Area at Baseline will be between a minimum of 10% and maximum of 90% of the total body surface area (BSA; 1% BSA is approximately equal to the surface area of the subject’s palm and fingers, with the fingers extended yet grouped together, creating a flat oval-like surface area). • For the Optional Maximal Use arm: The amount of CI affected skin in the Treatment Area at Baseline will be between a minimum of 75% and maximum of 90% of the total BSA. • For the Optional Maximal Use arm: The amount of CI affected skin in the Treatment Area at Baseline will be between a minimum of 75% and maximum of 90% of the total BSA. 6. Documented history of moderate to severe disease at Screening. Subject’s designated Visual Index for Ichthyosis Severity (VIIS) Assessment Areas at Baseline (not applicable for Optional Maximal Use arm) MUST: • Include any of the 4 VIIS Assessment Areas that have some CI disease involving: (a) the upper back from the posterior axillary fold to the other encompassing the T1-T10, (b) the upper arm (excluding elbows), left or right,(c) the shin/lower leg (the portion below the proximal aspect of the kneecap), left or right, and (d) dorsal foot (left or right); AND • At least 2 of the 4 VIIS Assessment Areas MUST have a scaling score of 3 or more. 7. Subject’s IGA score in the Treatment Area at Baseline must be 3 or more. 8. Subject and parent/guardian (if applicable) are willing and able to apply the study treatment(s) as directed, comply with study instructions, and commit to all follow-up vi
Exclusion criteria
Exclusion criteria: A subject is ineligible to enter the study if he/she meets 1 or more of the following exclusion criteria: 1. Subject is pregnant, lactating, or is planning to become pregnant during the study. 2. Subject has inflammatory skin diseases that confound the interpretation of results (e.g., atopic dermatitis) unrelated to ichthyosis. 3. Subject has phenotypic clinical presentations and/or genetic abnormality consistent with non-lamellar type or syndromic ichthyoses (including but not exclusively KRT1, KRT10, KRT2, GJB3, GJB4, CDSN). 4. Subject, in the Treatment Areas, has used: (a) any topical prescription or over-the-counter therapies (except emollients, keratolytics, and topical steroids - see below), that are intended for, or that in the opinion of the Investigator, may improve CI within 2 weeks of Visit 2 (Baseline), or (b) keratolytics or topical corticosteroids within 5 days prior to Visit 2 (Baseline). 5. Subject, in the Treatment Areas, has used TMB-001 in the past or oral isotretinoin in the past 12 months (not applicable for Optional Maximal Use arm) 6. Subject has used any topical products in the Treatment Areas, including bland emollients, on Visit 2 (Baseline). 7. Subject has used ultraviolet treatment within 4 weeks prior to Visit 2 (Baseline). 8. Subject has undergone systemic therapies using vitamin A supplements or St. John’s Wort within 4 weeks prior to Visit 2 (Baseline). Note: Use of a multivitamin including vitamin A is not exclusionary provided it is taken as directed on the packaging. 9. Subject is immunosuppressed (e.g., human immunodeficiency virus, systemic malignancy, graft host disease) or receives systemic immunotherapy. 10. Subject is currently taking concomitant immunosuppressive drugs, including systemic corticosteroids, within 2 weeks of Visit 2 (Baseline). 11. Subject has untreated secondary infections; however, subject may become eligible after successful treatment of his/her infection(s) at the Investigator’s discretion. 12. Subject is currently enrolled in an investigational drug or device study or has used an investigational drug or investigational device treatment within 30 days or five half-lives prior to Visit 2 (Baseline). 13. Subject has lesions suspicious for skin cancer (if skin cancer is not ruled out by biopsy) or untreated skin cancers within the Treatment Areas. 14. Subject has a physical condition or other dermatologic disorder that, in the Investigator’s opinion, might impair evaluation of CI, or that exposes the subject to unacceptable risk by study participation. 15. Subjects with ALT or AST >2 x Upper Limit of Normal (ULN) and/or creatinine >1.5 x ULN. 16. Subject is unable to communicate or cooperate with the Investigator due to language problems, impaired cerebral function, or physical limitations. 17. Subject has a history of drug or alcohol abuse within the past 6 months, or if suspected to be noncompliant or is unlikely to comply with the requirements of the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in the opinion of the Investigator. 18. Subject has a history of sensitivity to any of the ingredients in the study treatments. 19. Subject has been placed in an institution due to an official or judicial order. 20. Minor Subjects who are incapable of giving consent after reaching the age of majority.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Primary Objective To ascertain the efficacy of TMB-001 0.05% topical ointment as a treatment for CI compared with Vehicle during a 12-week treatment. ;Secondary Objective: • Key Secondary Efficacy Objectives 1. To ascertain the efficacy of TMB-001 0.05% topical ointment at Week 12 using the VIIS-50 scaling score. 2. To ascertain the efficacy of TMB-001 0.05% topical ointment at Week 12 using the IGA-scaling and fissuring scores. • Other Secondary Efficacy Objectives 4. To ascertain the efficacy of TMB-001 0.05% topical ointment at Week 12 using different levels of VIIS-scaling and IGA-scaling and fissuring scores. 5. To determine optimal maintenance therapy with TMB-001 0.05% topical ointment using the IGA-scaling and fissuring scores. 6. To determine optimal maintenance therapy with TMB-001 0.05% topical ointment using VIIS-scaling scores. • Patient-reported Outcome Measures • Safety Objective • Patient-reported Outcome Measures 7. To evaluate the effect of TMB-001 0.05% topical ointment on subject Quality of Life (QoL) during the 12-week treatment period and subsequent 12-week maintenance period. ;Primary end point(s): Comparison of proportions of subjects with =2-point changes from Baseline in IGA-scaling and fissuring scores in the Treatment Area at Week 12 between TMB-001 0.05% and vehicle-treated subjects.;Timepoint(s) of evaluation of this end point: Baseline and Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Comparison of proportion of subjects who achieve 50% reduction from Baseline in VIIS-scaling scores at Week 12 in all areas with Baseline VIIS score =3 between TMB-001 0.05% and vehicle-treated subjects. 2a. Comparison of proportion of subjects with IGA-scaling and fissuring scores of clear or almost clear at Week 12 between TMB-001 0.05% and vehicle-treated subjects. 2b. Comparison of proportion of subjects who achieve IGA-scaling severity sub-score improvements >2 points from Baseline to Week 12 between TMB-001 0.05% and vehicle-treated subjects. 3. Comparison of proportion of subjects with >4 point improvement from baseline in Worst Itch-QoL scores at week 12 in subjects with baseline Itch-Numeric Rating Scale (I-NRS) of >7 between TMB 001 0.05% and vehicle-treated subjects. • Other Secondary Efficacy Endpoints 4a. Comparison of proportion of subjects who achieve 25% reduction from Baseline in VIIS-scaling scores at Week 12 in all areas with Baseline VIIS score =3 between TMB-001 0.05% and vehicle-treated subjects. 4b. Comparison of proportion of subjects achieving >2 point improvement in IGA-fissuring severity sub-scores from Baseline to Week 12 between TMB-001 0.05% and vehicle-treated subjects. 5. Comparison of proportion of subjects achieving >2-point improvement from Baseline in IGA-scaling and fissuring scores at Week 24 between subjects randomized to TMB-001 0.05% BID and QD maintenance dosing. 6. Comparison of proportion of subjects who achieve 50% reduction from Baseline in VIIS-scaling scores at Week 24 in all areas with Baseline VIIS score =3 between subjects randomized to TMB-001 0.05% BID and QD maintenance dosing. • Patient-reported Outcome Endpoints 7a. Comparison of proportions of subjects with >11-point changes from Baseline in IQOL-32 scores at Week 12 between TMB-001 0.05% and vehicle-treated subjects. 7c. Comparison of proportion of subjects with reduction from Baseline in DLQI or CDLQI =4 points at Week 12 between | — |
Countries
Canada, France, Germany, Italy, United States
Contacts
Public ContactJessica Raiz
Timber Pharmaceuticals, LLC
Outcome results
None listed