The ASCEND Study: Evaluating TMB-001 in the Treatment of RXLI or ARCI Ichthyosis

NCT05295732 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: TMB01-3012022-000459-35
• Study Type: interventional
• Target: 153
• Locations: 5 countries
• Sites: 35

Brief Summary

This is a randomized, double-blind and vehicle-controlled Phase III study to evaluate the safety and efficacy of topical TMB-001 0.05% ointment for the treatment of congenital ichthyosis (CI) in subjects with either the RXLI or ARCI subtypes. In addition, a subset of preselected centers will recruit subjects in parallel with either the RXLI or ARCI subtypes for enrollment into an Optional Maximal Use arm for evaluation of the systemic exposure and safety of topical TMB-001 0.05% ointment for the treatment of CI. The Phase III Study is designed in three periods: \- Period 1 - Induction (3 weeks): At the beginning of the 3-week Induction Period, eligible subjects will be randomized (2:1 ratio) to either TMB-001 0.05% once-a-day (QD) or Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™) provided by the Sponsor. \- Period 2 - Treatment (9 weeks): The dosing frequency in the 9-week treatment period will be increased in each treatment group to TMB-001 0.05% BID or Vehicle BID. Mandatory bland emollient will be discontinued. \- Period 3 - Maintenance (12 weeks): At Week 12, eligible subjects in the TMB-001 treatment group will be randomized (1:1 ratio) to an open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. To be eligible, subjects must have achieved a ≥1-point reduction in IGA score from Baseline. Subjects with less than a 1-point reduction in IGA score from Baseline will be discontinued from the study. Vehicle-treated subjects who achieved \<1-point reduction in IGA score from Baseline are eligible to cross over to the TMB-001 0.05% BID treatment group. Subjects with a ≥1-point reduction in IGA score from Baseline on vehicle will be discontinued from the study. Subjects at the end of the study or subjects discontinued from the study at any time will be followed-up for additional 2 weeks for AEs.

Conditions

Ichthyosis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (30)

• Number of Subjects With IGA Scores

  12 weeks

• Change in IGA-scaling Severity Sub-score

  12 weeks

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

  12 weeks

• Change in Visual Index of Ichthyosis Severity (VIIS) Score

  12 weeks

• Change in VIIS Score

  12 weeks

Study Arms (3)

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

Interventions

TMB-001 DRUG

Topical TMB-001 0.05% QD/BID

Maximal use; TMB-001 0.05%

Matching Vehicle DRUG

Topical Vehicle

Vehicle

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Timber Pharmaceuticals Inc.: lead
• LEO Pharma: collaborator

Study Sites (35)

U.S. Dermatology Partners

Phoenix, Arizona, 85006, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

About Skin Dermatology

Centennial, Colorado, 80111, United States

Location

Yale Center for Clinical Investigation

New Haven, Connecticut, 06519, United States

Location

Department of Dermatology and Cutaneous Surgery, University of Miami

Miami, Florida, 33136, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Dawes Fretzin Clinical Research Group, LLC

Indianapolis, Indiana, 46250, United States

Location

The Indiana Clinical Trials Center

Plainfield, Indiana, 46168, United States

Location

Associated Skincare Specialists

New Brighton, Minnesota, 55112, United States

Location

University of Mississippi Medical Center (UMMC)

Jackson, Mississippi, 39216, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27104, United States

Location

Optima Research

Boardman, Ohio, 44512, United States

Location

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Austin Institute for Clinical Research

Houston, Texas, 77056, United States

Location

Austin Institute for Clinical Research, Inc.

Pflugerville, Texas, 78660, United States

Location

Virginia Clinical Research-Pariser Dermatology Specialists

Norfolk, Virginia, 23502, United States

Location

North Sound Dermatology

Mill Creek, Washington, 98012, United States

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Dr. Chih-ho Hong Medical Inc.

Surrey, British Columbia, V3R 6A7, Canada

Location

Wiseman Dermatology Research Inc.

Winnipeg, Manitoba, R3M 3Z4, Canada

Location

SickKids Hospital

Toronto, Ontario, M5G 1X8, Canada

Location

Hôpital Femme Mère Enfant

Bron, 69677, France

Location

CHU de Nantes Hotel Dieu

Nantes, 44093, France

Location

Hopital Necker APHP

Paris, 75015, France

Location

Hopital Larrey CHU Toulouse

Toulouse, 31059, France

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Katholisches Kinderkrankenhaus Wilhelmstift GmbH

Hamburg, 22149, Germany

Location

Münster University Hospital

Münster, 48149, Germany

Location

U.O. di Dermatologia e Venereologia Universitaria

Bari, 70124, Italy

Location

U.O. di Dermatologia Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale

Bologna, 40138, Italy

Location

Ambulatorio di Malattie Rare Dermatologiche e Immunopatologia Cutanea

Florence, 50125, Italy

Location

Fondazione IRCCS Ospedale Maggiore Policlinico Milano, Area Materno Infantile - SC pediatria Pneumoinfettivologia

Milan, Italy

Location

U.O.C. di Dermatologia Dipartimento Pediatrico Universitario Ospedaliero

Roma, 00165, Italy

Location

Related Publications (1)

• 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.

  PMID: 41406959 BACKGROUND

MeSH Terms

Conditions

Ichthyosis

Condition Hierarchy (Ancestors)

Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Clinical Disclosure
• Organization: LEO Pharma A/S

disclosure@leo-pharma.com

+4544945888

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: • Period 1 - Induction (3 weeks): At the beginning of the 3-week Induction Period, eligible subjects will be randomized (2:1 ratio) to either TMB-001 0.05% once-a-day (QD) or Vehicle QD treatment, with use of mandatory standardized bland emollient (Cetaphil™) provided by the Sponsor. • Period 2 - Treatment (9 weeks): The dosing frequency in the 9-week treatment period will be increased in each treatment group to TMB-001 0.05% BID or Vehicle BID. Mandatory bland emollient will be discontinued. • Period 3 - Maintenance (12 weeks): At Week 12, eligible subjects in the TMB-001 treatment group will be randomized (1:1 ratio) to an open-label treatment with TMB-001 0.05% BID or TMB-001 0.05% QD. Vehicle-treated subjects who achieved \<1-point reduction in IGA score from Baseline are eligible to cross over to the TMB-001 0.05% BID treatment group.

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: March 25, 2022
• Study Start: June 21, 2022
• Primary Completion: June 17, 2024
• Study Completion: September 23, 2024
• Last Updated: March 20, 2026
• Results First Posted: November 17, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (18); CA (4); DE (4); FR (4); IT (5)