The ASCEND Study: Evaluating TMB-001 in the Treatment of... | NCT05295732

ID	Type	Description	Link
2022-000459-35	EudraCT Number

Description Module

Detailed Description

This is a multicenter, randomized, double-blind, vehicle-controlled Phase III study to evaluate the efficacy and safety of TMB-001 0.05% topical ointment in the treatment of CI. Subjects will be selected according to predefined entry criteria. The study treatment duration is 24 weeks and expected to be sufficient to show a treatment effect.

Isotretinoin is an approved active pharmacological ingredient with a long history of safe use in humans. However, isotretinoin is a known teratogen with an extremely high risk for severe birth defects if pregnancy occur while taking oral isotretinoin in any amount, even for a short period of time. Therefore oral, systemic isotretinoin requires an iPLEDGE program (iPLEDGE 2012), which is a risk management distribution program mandated by the FDA. To minimize pregnancy risks, women of childbearing potential (WOCBP) will only be enrolled if they agree to use highly effective methods of contraception consistently and correctly and undergo regular pregnancy testing.

To minimize bias, subjects will be blinded and randomly assigned to treatment with TMB-001 0.05% or Vehicle, additionally subjects who had previously been treated with TMB 001 will be excluded from this study but can be enrolled in the optional Maximal Use arm (in a subset of preselected centers). The use of a vehicle control group is consistent with FDA's standard for generating valid scientific evidence to definitively support safety and efficacy. The vehicle group accounts for the effects of treatment that do not depend on the test treatment. The study is designed to mitigate safety risks by using an initial 2:1 randomization (active treatment to vehicle), along with frequent clinic visits over the 12-week treatment period. The subsequent 1:1 randomization of eligible TMB-001 0.05% treated subjects to two dosing regimen (QD or BID) allows for assessment of the optimal TMB-001 0.05% maintenance therapy as well as provides additional safety data for 12 weeks. The cross-over of eligible subjects from the vehicle control group will also provide additional safety data.

Overall, the study design is considered to be scientifically robust and clinically relevant for evaluating TMB-001 0.05% treatment for the safe and effective treatment of CI.

Label	Type	Description	Intervention Names
TMB-001 0.05%	Experimental	TMB-001 0.05% ointment: Induction phase QD for 3 weeks, followed by BID for 9 weeks. Maintenance therapy for additional 12 weeks randomized QD vs BID	Drug: TMB-001
Vehicle	Placebo Comparator	Matching vehicle ointment: Induction phase QD for 3 weeks, followed by BID for 9 weeks. Cross over to 12 weeks TMB-001 0.05% BID.	Drug: Matching Vehicle
Maximal use	Experimental	Optional Parallel Arm to evaluate the systemic exposure and safety of TMB-001 0.05% under conditions of maximal use.	Drug: TMB-001

Name	Type	Description	Arm Group Labels	Other Names
TMB-001	Drug	Topical TMB-001 0.05% QD/BID	Maximal use TMB-001 0.05%

Measure	Description	Time Frame
Change in Investigator Global Assessment (IGA) Score	Comparison of proportions of subjects in percentages with ≥2-point changes from Baseline in Investigator Global Assessment (IGA)-scaling and fissuring scores in the Treatment Area at Week 12 between TMB-001 0.05% and vehicle-treated subjects. Investigator's Global Assessment Score is a 0-4 scale, where 0 is clear and 4 is severe.	12 weeks

Measure	Description	Time Frame
Number of Subjects With IGA Scores	Comparison of proportion of subjects in percentages with IGA scores of clear or almost clear at Week 12 between TMB-001 0.05% and vehicle-treated subjects. Investigator's Global Assessment Score is a 0-4 scale, where 0 is clear and 4 is severe.	12 weeks
Change in IGA-scaling Severity Sub-score

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject is male or female, 6 years of age and older at Visit 2 (Baseline).
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.
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. 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 [β hCG]/mL). 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.
Subject has clinical diagnosis of CI 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-LI 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.
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 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.
Documented history of moderate to severe disease at Screening. Subject's designated VIIS Assessment Areas at Baseline (not applicable for Optional Maximal Use arm):
- 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.
Subject's IGA score in the Treatment Area at Baseline must be 3 or more.
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 visits for the duration of the study.
Subject, in the Investigator's opinion, is in good general health and free of any disease state or physical condition that might impair evaluation of the Treatment Areas or exposes the subject to an unacceptable risk by study participation.

Exclusion Criteria:

Subject is pregnant, lactating, or is planning to become pregnant during the study.
Subject has inflammatory skin diseases that confound the interpretation of results (e.g., atopic dermatitis) unrelated to ichthyosis.
Subject has genetic abnormality consistent with non-lamellar type or syndromic ichthyoses (including but not exclusively KRT1, KRT10, KRT2, GJB3, GJB4, CDSN)
Subject, in the Treatment Areas, has used: (a) any topical prescription or over-the-counter (OTC) 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).
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).
Subject has used any topical products in the Treatment Areas, including bland emollients, on Visit 2 (Baseline).
Subject has used ultraviolet (UV) treatment within 4 weeks prior to Visit 2 (Baseline).
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.
Subject is immunosuppressed (e.g., human immunodeficiency virus, systemic malignancy, graft host disease) or receives systemic immunotherapy.
Subject is currently taking concomitant immunosuppressive drugs, including systemic corticosteroids, within 2 weeks of Visit 2 (Baseline).
Subject has untreated secondary infections; however, subject may become eligible after successful treatment of his/her infection(s) at the Investigator's discretion.
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).
Subject has lesions suspicious for skin cancer (if skin cancer is not ruled out by biopsy) or untreated skin cancers within the Treatment Areas.
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.
Subjects with ALT or AST >2 x Upper Limit of Normal (ULN) and/or creatinine >1.5 x ULN.
Subject is unable to communicate or cooperate with the Investigator due to language problems, impaired cerebral function, or physical limitations.
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.
Subject has a history of sensitivity to any of the ingredients in the study treatments.

Facility	Status	City	State	ZIP	Country	Contacts
U.S. Dermatology Partners		Phoenix	Arizona	85006	United States
Stanford University School of Medicine

PubMed Identifier	Type	Citation	Retractions
41406959	Background	Schneider H, Bunick CG, Hillmann K, Huynh TN, Kempers S, Peschel N, Blume-Peytavi U, Teng JMC, Mendelsohn AM, Stinson J, Lee LW. Maximal use of 0.05% topical isotretinoin in patients with congenital ichthyosis results in low systemic exposure. Br J Clin Pharmacol. 2026 Apr;92(4):1256-1260. doi: 10.1002/bcp.70423. Epub 2025 Dec 17.

ID	Title	Description
FG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 25, 2022	Jun 11, 2025

Arm/Group Information

ID	Title	Description
BG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
BG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
BG002	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14> days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Investigator Global Assessment (IGA) Score

Comparison of proportions of subjects in percentages with ≥2-point changes from Baseline in Investigator Global Assessment (IGA)-scaling and fissuring scores in the Treatment Area at Week 12 between TMB-001 0.05% and vehicle-treated subjects. Investigator's Global Assessment Score is a 0-4 scale, where 0 is clear and 4 is severe.

For the primary efficacy endpoint, missing Week 12 IGA scores were imputed by a multiple imputation approach and IGA responder status was derived from the imputed values. The analysis was then performed on each of the 50 imputed datasets. The final proportion of responders is the average proportion across all 50 imputed datasets hence the proportion is not an exact fraction of the total number of subjects.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Units	Counts
Participants	OG00078 OG00138

Title

Denominators

Categories

Title	Measurements
	OG00041.4 OG00144.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		0.39		treatment difference	-1.0			2-Sided	95	-18.4	16.5					Superiority

Secondary

Number of Subjects With IGA Scores

Comparison of proportion of subjects in percentages with IGA scores of clear or almost clear at Week 12 between TMB-001 0.05% and vehicle-treated subjects. Investigator's Global Assessment Score is a 0-4 scale, where 0 is clear and 4 is severe.

Missing values were imputed by a multiple imputation approach and the final proportion of responders is the average proportion across all imputed datasets, hence the proportion is not an exact fraction of the total number of subjects.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Secondary

Change in IGA-scaling Severity Sub-score

Comparison of proportion of subjects in percentages who achieve IGA-scaling severity sub-score improvement ≥ 2-points from Baseline to Week 12 between TMB-001 0.05% and vehicle-treated subjects. Investigator's Global Assessment Score is a 0-4 scale, where 0 is clear and 4 is severe.

Data is not available for 3 participants in the TMB-001 0.05% group and for 2 participants in the vehicle group. Missing values were imputed by a multiple imputation approach and the final proportion of responders is the average proportion across all imputed datasets, hence the proportion is not an exact fraction of the total number of subjects.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Secondary

Change in Worst Itch-Quality of Life (QoL) Scores

Comparison of proportion of subjects in percentages with ≥4-point improvement from baseline in Worst Itch-QoL scores at Week 12 in subjects with baseline WI-NRS of ≥7 between TMB-001 0.05% and vehicle-treated subjects. Itch-Numeric Rating Scale (I-NRS) and Worst Itch-Numeric Rating Scale (WI-NRS) is an 0-10 scale where 0 is "no itching" and 10 is "worst itch imaginable".

Data is not available for 59 participants in the TMB-001 0.05% group and for 29 participants in the vehicle group. Missing values were imputed by a multiple imputation approach and the final proportion of responders is the average proportion across all imputed datasets, hence the proportion is not an exact fraction of the total number of subjects.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Secondary

Change in Visual Index of Ichthyosis Severity (VIIS) Score

Comparison of proportion of subjects in percentages 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. Visual Index for Ichthyosis Severity Score is a 0-4 scale where 0 is clear and 4 is severe.

Data is not available for 4 participants in the TMB-001 0.05% group. Missing values were imputed by a multiple imputation approach and the final proportion of responders is the average proportion across all imputed datasets, hence the proportion is not an exact fraction of the total number of subjects.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Secondary

Change in VIIS Score

Comparison of proportion of subjects in percentages 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. Visual Index for Ichthyosis Severity Score is a 0-4 scale where 0 is clear and 4 is severe.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Secondary

Change in IGA-fissuring Severity Sub-scores

Comparison of proportion of subjects in percentages achieving ≥2 point improvement in IGA-fissuring severity sub-scores from Baseline to Week 12 between TMB-001 0.05% and vehicle-treated subjects. Investigator's Global Assessment Score is a 0-4 scale, where 0 is clear and 4 is severe.

Data is not available for 48 participants in the TMB-001 0.05% group and for 21 participants in the vehicle group. Missing values were imputed by a multiple imputation approach and the final proportion of responders is the average proportion across all imputed datasets, hence the proportion is not an exact fraction of the total number of subjects.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Secondary

Change in IGA Score

Comparison of proportions of subjects in percentages achieving ≥2-point improvement from Baseline in IGA scores at Week 24 between subjects randomized to TMB-001 0.05% BID and QD maintenance dosing. Investigator's Global Assessment Score is a 0-4 scale, where 0 is clear and 4 is severe.

Data reported for the re-randomized TMB-001 0.05% responders subjects in TMB-001 0.05% BID group. Missing values were imputed by a multiple imputation approach and the final proportion of responders is the average proportion across all imputed datasets, hence the proportion is not an exact fraction of the total number of subjects.

Posted

Number

95% Confidence Interval

percentage of responders

24 weeks

ID	Title	Description
OG000	TMB-001 0.05% QD	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001> 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment> with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were> discontinued from the study.
OG001	TMB-001 0.05% BID	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.

Secondary

Change in VIIS Score

Comparison of proportion of subjects in percentages 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. Visual Index for Ichthyosis Severity Score is a 0-4 scale where 0 is clear and 4 is severe.

Posted

Number

95% Confidence Interval

percentage of responders

24 weeks

ID	Title	Description
OG000	TMB-001 0.05% QD	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.
OG001	TMB-001 0.05% BID

Secondary

Change in Ichthyosis Quality of Life (IQoL)-32 Scores

Comparison of proportions of subjects in percentages with ≥11-point changes from Baseline in IQOL-32 scores at Week 12 between TMB-001 0.05% and vehicle-treated subjects. The IQoL-32 is a questionnaire containing 32, each scored from 0 to 4 ('not applicable', 'not at all', 'a little', 'a lot', 'tremendously') for a total score that varies between 0 and 128. A higher score, the higher impact on quality of life.

Data is not available for 44 participants in the TMB-001 0.05% group and for 17 participants in the vehicle group.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Secondary

Change in Dermatology Life Quality Index (DLQI) Scores

Comparison of proportion of subjects in percentages with reduction from Baseline in DLQI ≥4 points at Week 12 between TMB-001 0.05% and vehicle-treated subjects in adult subjects with Baseline scores ≥11. The age-appropriate questionnaire contains 10 questions scored from 0 (no impact of skin disease on QoL) to 30 (maximum impact on QoL).

Data is not available for 63 participants in the TMB-001 0.05% group and for 30 participants in the vehicle group.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Secondary

Change in Children's Dermatology Life Quality Index (CDLQI) Scores

Comparison of proportion of pediatric subjects in percentages with reduction from Baseline in CDLQI ≥4 points at Week 12 between TMB-001 0.05% and vehicle-treated subjects in pediatric subjects with Baseline scores of ≥13. The age-appropriate questionnaire contains 10 questions scored from 0 (no impact of skin disease on QoL) to 30 (maximum impact on QoL).

Only 5 pediatric subjects had Baseline scores of ≥13 in the TMB-001 0.05% group. No pediatric subjects had Baseline scores of ≥13 in the vehicle group.

Posted

Number

percentage of responders

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Secondary

Change in Itch-Quality of Life Scores - I-NRS

Comparison of proportions of subjects in percentages with I-NRS improvement ≥4 points from Baseline in Itch-QoL scores (in subjects with Baseline I-NRS ≥7) at Week 24 between subjects randomized to TMB-001 0.05% BID and QD maintenance dosing.

No participants in the TMB-001 0.05% QD Group had Baseline I-NRS scores ≥7 and therefore, 0 participants in this Group were analyzed for this measure. Data is not available for 37 participants in the TMB-001 0.05% BID group.

Posted

Number

95% Confidence Interval

percentage of responders

24 weeks

ID	Title	Description
OG000	TMB-001 0.05% QD	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline were discontinued from the study.
OG001	TMB-001 0.05% BID	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline were discontinued from the study.

Secondary

Change in Itch-Quality of Life Scores - WI-NRS

Comparison of proportions of subjects in percentages with WI-NRS improvement ≥4 points from Baseline in Itch-QoL scores (in subjects with Baseline WI-NRS ≥7) at Week 24 between subjects randomized to TMB-001 0.05% BID and QD maintenance dosing.

Data is not available for 25 participants in the TMB-001 0.05% QD group and for 23 participants in the TMB-001 0.05% BID group. In addition, 11 participants in the TMB-001 0.05% BID group randomized to vehicle in the double-blinded period were not included. Missing values were imputed by a multiple imputation approach and the final proportion of responders is the average proportion across all imputed datasets, hence the proportion is not an exact fraction of the total number of subjects.

Posted

Number

95% Confidence Interval

percentage of responders

24 weeks

ID	Title	Description
OG000	TMB-001 0.05% QD	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.
OG001	TMB-001 0.05% BID

Secondary

Change in DLQI Scores

Comparison of proportions of adult subjects in percentages with DLQI changes of ≥4-point from Baseline scores (in subjects with Baseline scores ≥11) at Week 24 randomized to TMB-001 0.05% BID and QD maintenance dosing. The age-appropriate questionnaire contains 10 questions scored from 0 (no impact of skin disease on QoL) to 30 (maximum impact on QoL).

Data is not available for 24 participants in the TMB-001 0.05% QD group and for 23 participants in the TMB-001 0.05% BID group. In addition, 11 participants in the TMB-001 0.05% BID group randomized to vehicle in the double-blinded period were not included.

Posted

Number

95% Confidence Interval

percentage of responders

24 weeks

ID	Title	Description
OG000	TMB-001 0.05% QD	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.
OG001	TMB-001 0.05% BID	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.

Secondary

Change in CDLQI Scores

Comparison of proportions of pediatric subjects in percentages with CDLQI changes of ≥4-point from Baseline scores (in subjects with Baseline scores ≥13) at Week 24 randomized to TMB-001 0.05% BID and QD maintenance dosing. The age-appropriate questionnaire contains 10 questions scored from 0 (no impact of skin disease on QoL) to 30 (maximum impact on QoL).

Only 1 pediatric subjects had Baseline scores of ≥13 in the TMB-001 0.05% QD group, and 3 pediatric subjects had Baseline scores of ≥13 in the TMB-001 0.05% BID group.

Posted

Number

95% Confidence Interval

percentage of responders

24 weeks

ID	Title	Description
OG000	TMB-001 0.05% QD	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.
OG001	TMB-001 0.05% BID	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline on vehicle were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline were discontinued from the study.

Secondary

Change in IQoL-32 Scores

Proportions of subjects in percentages with ≥11-point change from Baseline in IQoL-32 at Week 24 between subjects randomized to TMB-001 0.05% BID and QD maintenance dosing in adult subjects. The IQoL-32 is a questionnaire containing 32, each scored from 0 to 4 ('not applicable', 'not at all', 'a little', 'a lot', 'tremendously') for a total score that varies between 0 and 128. A higher score, the higher impact on quality of life.

Data is not available for 18 participants in the TMB-001 0.05% QD group and for 17 participants in the TMB-001 0.05% BID group. In addition, 11 participants in the TMB-001 0.05% BID group randomized to vehicle in the double-blinded period were not included.

Posted

Number

95% Confidence Interval

percentage of responders

24 weeks

ID	Title	Description
OG000	TMB-001 0.05% QD	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline on vehicle were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline were discontinued from the study.
OG001	TMB-001 0.05% BID

Secondary

To Investigate the Proportion of Subjects Experiencing Local Skin Reactions (LSRs) With Topically Applied TMB-001 0.05% Ointment.

Comparison of proportion of subjects in percentages experiencing LSRs through Week 12 between TMB-001 0.05% and vehicle-treated subjects.

Posted

Number

95% Confidence Interval

percentage of participants

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Units	Counts

Secondary

To Investigate the Proportion of Subjects Experiencing Treatment-emergent Adverse Events (TEAEs)

Comparison of proportion of subjects in percentages experiencing TEAEs through Week 12 between TMB-001 0.05% and vehicle-treated subjects.

Posted

Number

percentage of participants

12 weeks

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Units	Counts
Participants

Secondary

To Investigate the Proportion of Subjects Experiencing LSRs With Topically Applied TMB-001 0.05% Ointment.

Comparison of proportion of subjects in percentages experiencing LSRs through Week 24 between subjects randomized to TMB-001 0.05% BID and QD maintenance dosing.

Data reported for the re-randomized TMB-001 0.05% responders subjects in TMB-001 0.05% BID group.

Posted

Number

95% Confidence Interval

percentage of participants

24 weeks

ID	Title	Description
OG000	TMB-001 0.05% QD	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.
OG001	TMB-001 0.05% BID	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.

Secondary

To Investigate the Proportion of Subjects Experiencing TEAEs

Comparison of proportion of subjects in percentages experiencing TEAEs through Week 24.

Data reported for the re-randomized TMB-001 0.05% responders subjects in TMB-001 0.05% BID group.

Posted

Number

95% Confidence Interval

percentage of participants

24 weeks

ID	Title	Description
OG000	TMB-001 0.05% QD	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.
OG001	TMB-001 0.05% BID	At Week 12, TMB-001 0.05% BID treatment responders (who had achieved a ≥1-point reduction in IGA score from baseline) were re-randomized (1:1 ratio) to 12 weeks of open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Subjects with less than a 1-point reduction in IGA score from baseline were discontinued from the study. Vehicle-treated subjects who achieved <1-point reduction in IGA score from baseline by week 12, were eligible to cross over to 12 weeks of open-label treatment with TMB-001 0.05% BID treatment. Subjects with a ≥1-point reduction in IGA score from baseline on vehicle were discontinued from the study.

Secondary

To Investigate the Proportion of Subjects Demonstrating Clinically Confirmed Allergic Contact Dermatitis

Comparison of proportion of subjects in percentages demonstrating clinically confirmed allergic contact dermatitis by patch testing through Week 12 between TMB-001 0.05% and vehicle-treated subjects.

Posted

Number

percentage of participants

Through week 12

ID	Title	Description
OG000	TMB-001 0.05%	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to TMB-001 0.05% QD with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12 week double-blind primary dosing period, the subjects continued with TMB-001 0.05% at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.
OG001	Vehicle	In the first 3 weeks of the 12-week double-blind primary dosing period, subjects were randomized to Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™). For the last 9 weeks of the 12-week double-blind primary dosing period, the subjects continued with Vehicle at the increased dosing frequency of BID. Mandatory bland emollient was discontinued.

Units	Counts

Secondary

Maximal Use Arm: Isotretinoin, Tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin - Cmax After Multiple Dosing - Adults

maximal observed plasma concentration.

> Assessment of concentrations of isotretinoin, tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin.

Data is not available for 24 participants in the Maximal use group.

Posted

Mean

Standard Deviation

ng/mL

14 days

ID	Title	Description
OG000	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14 > days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.

Units	Counts
Participants

Secondary

Maximal Use Arm: Isotretinoin, Tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin - Cmax After Multiple Dosing - Adolescents

maximal observed plasma concentration.

> Assessment of concentrations of isotretinoin, tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin.

Data is not available for 32 participants in the Maximal use group.

Posted

Mean

Standard Deviation

ng/mL

14 days

ID	Title	Description
OG000	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14 > days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.

Units	Counts
Participants

Secondary

Maximal Use Arm: Isotretinoin, Tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin - AUC0-24 After Multiple Dosing - Adults

AUC0-24 = area under the curve over the first 24 hours post dose.

> Assessment of concentrations of isotretinoin, tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin.

Data is not available for 24 participants in the Maximal use group.

Posted

Mean

Standard Deviation

hr*ng/mL

0-24hrs after dose

ID	Title	Description
OG000	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14 > days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.

Units	Counts
Participants

Secondary

Maximal Use Arm: Isotretinoin, Tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin - AUC0-24 After Multiple Dosing - Adolescents

AUC0-24 = area under the curve over the first 24 hours post dose.

> Assessment of concentrations of isotretinoin, tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin.

Data is not available for 32 participants in the Maximal use group.

Posted

Mean

Standard Deviation

hr*ng/mL

0-24hrs after dose

ID	Title	Description
OG000	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14 > days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.

Units	Counts

Secondary

Maximal Use Arm: Isotretinoin, Tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin - Tmax After Multiple Dosing - Adults

Tmax = time to maximal plasma concentration.

> Assessment of concentrations of isotretinoin, tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin.

Data is not available for 24 participants in the Maximal use group.

Posted

Median

Full Range

hours

14 days

ID	Title	Description
OG000	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14 > days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.

Units	Counts
Participants

Secondary

Maximal Use Arm: Isotretinoin, Tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin - Tmax After Multiple Dosing - Adolescents

Tmax = time to maximal plasma concentration.

> Assessment of concentrations of isotretinoin, tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin.

Data is not available for 32 participants in the Maximal use group.

Posted

Median

Full Range

hours

14 days

ID	Title	Description
OG000	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14 > days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.

Units	Counts
Participants

Secondary

Maximal Use Arm: Isotretinoin, Tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin - Steady State Concentration After Multiple Dosing - Children

Assessment of concentrations of isotretinoin, tretinoin, 4-oxo-tretinoin and 4-oxo-isotretinoin.

Data is not available for 27 participants in the Maximal use group.

Posted

Mean

Standard Deviation

ng/mL

14 days

ID	Title	Description
OG000	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14 > days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.

Units	Counts
Participants

Secondary

Maximal Use Arm: Safety and Tolerability - LSRs

Local skin reactions (burnings/stinging, erythema, erosions and edema) are reported as LSRs.

Posted

Number

events

12 weeks

ID	Title	Description
OG000	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14> days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.

Units	Counts
Participants	OG000

Secondary

Maximal Use Arm: Safety and Tolerability - TEAEs

Local safety are reported as severe TEAEs related to treatment area.

Posted

Number

events

12 weeks

ID	Title	Description
OG000	Maximal Use	The optional maximal use arm part of the trial was conducted under the same protocol number for operational reasons, but with separate design, objective, and patients. Adult and pediatric subjects, at a subset of preselected centers, were enrolled in an open-label Optional Maximal Use Arm to evaluate the systemic exposure and safety of TMB-001 0.05% for the treatment of congenital ichthyosis under maximal use conditions. Initially, adult and pediatric subjects with congenital ichthyosis were dosed for 14 days with TMB-001 0.05% BID. Following an interim pharmacokinetic (PK) analysis and based on the exposure data for subjects aged ≥12 years, pediatric subjects aged 6 to 11 years began dosing with TMB-001 0.05% BID for 14> days. Following the 14-day PK assessment period, subjects received TMB-001 0.05% BID treatment for 10 weeks to provide additional safety and limited efficacy data.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Application site dermatitis	General disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected38 at risk EG0021 events1 affected28 at risk EG0032 events2 affected38 at risk EG0041 events1 affected34 at risk
Application site erosion	General disorders	MedDRA 25.0	Non-systematic Assessment	EG00018 events14 affected78 at risk EG0012 events2 affected38 at risk EG0020 events0 affected28 at risk EG003
Application site erythema	General disorders	MedDRA 25.0	Non-systematic Assessment	EG00039 events27 affected78 at risk EG0014 events4 affected38 at risk EG0027 events5 affected28 at risk EG003
Application site oedema	General disorders	MedDRA 25.0	Non-systematic Assessment	EG0007 events6 affected78 at risk EG0011 events1 affected38 at risk EG0020 events0 affected28 at risk EG003
Application site pain	General disorders	MedDRA 25.0	Non-systematic Assessment	EG00041 events23 affected78 at risk EG0016 events5 affected38 at risk EG0025 events4 affected28 at risk EG003
Application site pruritus	General disorders	MedDRA 25.0	Non-systematic Assessment	EG00014 events12 affected78 at risk EG0010 events0 affected38 at risk EG0020 events0 affected28 at risk EG003
Pyrexia	General disorders	MedDRA 25.0	Non-systematic Assessment	EG0003 events3 affected78 at risk EG0011 events1 affected38 at risk EG0021 events1 affected28 at risk EG003
COVID-19	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected38 at risk EG0021 events1 affected28 at risk EG003
Folliculitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected78 at risk EG0012 events2 affected38 at risk EG0020 events0 affected28 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0003 events1 affected78 at risk EG0012 events2 affected38 at risk EG0021 events1 affected28 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0005 events4 affected78 at risk EG0013 events3 affected38 at risk EG0023 events2 affected28 at risk EG003
Headache	Nervous system disorders	MedDRA 25.0	Non-systematic Assessment	EG0008 events7 affected78 at risk EG0013 events1 affected38 at risk EG0020 events0 affected28 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected78 at risk EG0012 events2 affected38 at risk EG0020 events0 affected28 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0006 events6 affected78 at risk EG0010 events0 affected38 at risk EG0020 events0 affected28 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0003 events3 affected78 at risk EG0012 events2 affected38 at risk EG0020 events0 affected28 at risk EG003

ID	Term
D012868	Skin Abnormalities
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases
D007642	Keratosis
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Double-blinded Phase: TMB-001 0.05%	Double-blinded phase: TMB-001 0.05% (N=78)	78	1	78	47	78
EG001	Double-blinded Phase: Vehicle	Double-blinded phase: Vehicle (N=38)	38	0	38	17	38
EG002	Open-label Phase: TMB-001 0.05% QD	Open-label phase: TMB-001 0.05% QD (N=28)	28	0	28	11	28
EG003	Open-label Phase: TMB-001 0.05% BID	Open-label phase: TMB-001 0.05% BID (N=38)	38	0	38	14	38
EG004	Maximal Use	Maximal use (N=34)	34	0	34	22	34