TMB-001 Ointment for Ichthyosis

(ASCEND Trial)

No longer recruiting at 49 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Timber Pharmaceuticals Inc.

Must not be taking: Retinoids, Immunosuppressants

Disqualifiers: Pregnancy, Inflammatory skin diseases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new ointment, TMB-001, for individuals with ichthyosis, a condition that causes dry, scaly skin. Researchers aim to determine if this ointment is safe and effective for treating two types of ichthyosis: RXLI and ARCI. Participants will apply the ointment daily or twice daily over several weeks to assess its effectiveness compared to a placebo. Suitable candidates have ichthyosis affecting 10-90% of their skin and a documented history of moderate to severe disease. As a Phase 3 trial, this is the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using certain topical treatments and therapies in the treatment areas before starting the study. Specifically, you must not use topical prescription or over-the-counter therapies (except emollients, keratolytics, and topical steroids) within 2 weeks before the study begins, and you must avoid keratolytics or topical corticosteroids within 5 days before starting. Additionally, you should not have used oral isotretinoin in the past 12 months or ultraviolet treatment within 4 weeks before the study.

Is there any evidence suggesting that TMB-001 ointment is likely to be safe for humans?

Research has shown that TMB-001 0.05% ointment was well-tolerated in past studies. One study found no serious safety concerns or signs of harmful absorption levels in the body. This indicates the treatment did not cause worrying side effects. Earlier trials also demonstrated positive results without major safety issues, suggesting that TMB-001 is generally safe for individuals with congenital ichthyosis, a genetic skin disorder causing dry, scaly skin. While ongoing studies will provide more information, current evidence suggests that TMB-001 is a safe option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ichthyosis?

Unlike the standard treatments for ichthyosis, which often involve moisturizing creams and systemic retinoids, TMB-001 ointment offers a targeted approach with its active ingredient: isotretinoin. This topical formulation allows for direct application to the skin, potentially reducing systemic side effects typically associated with oral retinoids. Researchers are excited because TMB-001's novel delivery method could provide effective relief with fewer side effects, while its flexible dosing schedule aims to optimize patient convenience and adherence. This innovative approach could significantly enhance quality of life for individuals with ichthyosis.

What evidence suggests that TMB-001 ointment might be an effective treatment for ichthyosis?

Research has shown that TMB-001 0.05% ointment may help treat congenital ichthyosis (CI). In earlier studies, patients using TMB-001 experienced much smoother skin with fewer cracks. The treatment appears safe, as past studies found no major changes in lab tests. In this trial, participants will receive TMB-001 0.05% ointment, which could be a promising alternative to oral retinoids, commonly used pills for skin conditions like CI. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for males and females aged 6 and older with a clinical diagnosis of Congenital Ichthyosis (CI), specifically RXLI or ARCI subtypes, confirmed by genetics. Participants must have significant skin scaling and be in good health. Women who can bear children must use two forms of birth control. Those pregnant, lactating, or planning pregnancy; using certain treatments like UV therapy or systemic immunosuppressants; with untreated infections; drug/alcohol abuse history; on other trials; failed retinoid therapies; liver/kidney issues are excluded.

Inclusion Criteria

I am 6 years old or older.

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

Your baseline assessment must show that specific areas have a score of 3 or higher.

Exclusion Criteria

I have a skin or physical condition that could affect the study's safety or results.

Your liver or kidney function tests are significantly higher than normal.

I am on immunotherapy or have a weakened immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Eligible subjects are randomized to TMB-001 0.05% or Vehicle treatment once daily for 3 weeks with mandatory use of a bland emollient

3 weeks

Treatment

Subjects receive TMB-001 0.05% or Vehicle treatment twice daily for 9 weeks

9 weeks

Maintenance

Eligible subjects in the TMB-001 group are randomized to open-label treatment with TMB-001 0.05% BID or QD for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TMB-001

Trial Overview The study tests TMB-001 ointment's safety and effectiveness against CI compared to a placebo (vehicle). It has three phases over 24 weeks: an initial induction period with once-daily treatment, increased to twice daily during the main treatment phase, followed by maintenance where dosing frequency may vary based on response. An optional arm studies systemic exposure in those with extensive affected skin.

How Is the Trial Designed?

Group I: TMB-001 0.05% Experimental Treatment 1 Intervention

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

Group II: Maximal use Experimental Treatment 1 Intervention

Optional Parallel Arm to evaluate the systemic exposure and safety of TMB-001 0.05% under conditions of maximal use.

Group III: Vehicle Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Timber Pharmaceuticals Inc.

Lead Sponsor

Trials

2

Recruited

240+

Timber Pharmceuticals LLC

Lead Sponsor

Trials

2

Recruited

240+

LEO Pharma

Industry Sponsor

Trials

275

Recruited

189,000+

Christophe Bourdon

LEO Pharma

Chief Executive Officer since 2022

Engineering degree from Université de Technologie de Compiègne

Dr. Siri Torhaug

LEO Pharma

Chief Medical Officer since 2022

MD, PhD

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37170057/

Topical Isotretinoin (TMB-001) Treatment for 12 Weeks Did ... There were no clinically significant laboratory changes in participants receiving TMB-001 isotretinoin ointment through 12 weeks of treatment.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05295732

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

3. conferences.medicom-publishers.com conferences.medicom-publishers.com/content/conference-reports/promising-first-results-of-novel-topical-treatment-for-congenital-ichthyosis/

Promising first results of novel topical treatment for congenital ... According to this preliminary data, TMB-001 led to statistically and clinically significant improvements in IGA scaling, fissuring, and combined ...

4. hcplive.com hcplive.com/view/christopher-bunick-efficacy-safety-tmb-001-treating-congenital-ichthyosis

Christopher Bunick, MD, PhD: Efficacy, Safety of TMB-001 ... Adult and adolescent patients—in the age range of 12-64 years—saw positive results from the use of the investigational drug TMB-001 (topical ...

5. jaad.org jaad.org/article/S0190-9622(22)02398-2/fulltext

The CONTROL study: A randomized, double-blind vehicle ... These results support ongoing TMB-001 efficacy and safety investigation as a promising alternative to oral retinoids for patients with CI.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10264299/

Topical Isotretinoin (TMB-001) Treatment for 12 Weeks Did ... In the Phase 2b study, the primary and key secondary efficacy endpoints—a 50% improvement in Visual Index for Ichthyosis Severity scaling scores ...

7. healio.com healio.com/news/dermatology/20220801/tmb001-yields-encouraging-results-in-congenital-ichthyosis-subtypes

TMB-001 yields encouraging results in congenital ... Fifty-five percent of participants in the TMB-001 0.05% group reached the endpoint of improvement of at least two points on the Investigators ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05295732

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