HT-001 for Skin Side Effects from Cancer Therapy

(CLEER Trial)

Recruiting at 11 trial locations

Overseen By Hayley Springer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoth Therapeutics, Inc.

Must be taking: EGFR inhibitors

Must not be taking: Neurokinin-1 antagonists, CYP3A4 inhibitors

Disqualifiers: Severe toxicity, Skin disorders, others

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

Compensation: Varies

Number of Visits: 1

152 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gel treatment called HT-001 to address skin issues caused by cancer therapy, specifically those related to an EGFR inhibitor. The main goals are to determine if the gel can reduce skin rashes and ensure its safety. Participants will apply the gel daily for six weeks, and researchers will compare its effects to a placebo to assess any differences. This trial suits individuals undergoing EGFR inhibitor therapy for cancer who have developed skin rashes from the treatment. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if they are stable. If you are on stable doses of topical or systemic antibiotics, steroids, or other treatments for 14 days or more, you can continue them. However, certain medications like pimozide, some antibiotics, and specific enzyme inhibitors or inducers should not be taken within 30 days before starting the trial.

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

Research has shown that HT-001 Topical Gel produced promising results in earlier studies. All patients using HT-001 experienced significant improvements in skin problems caused by EGFR inhibitors within six weeks. This suggests the treatment effectively manages skin issues related to cancer therapy.

Although detailed safety information on HT-001 remains limited, its progression to a trial phase focused on effectiveness and safety suggests earlier research found it well-tolerated. Treatments reaching this stage typically have not shown major safety concerns. However, like any treatment, side effects may occur, and further studies will help clarify these. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike other treatments for skin side effects from cancer therapy, HT-001 uses a topical gel formulation that could offer a new way to soothe and heal the skin directly where it's needed. Most current options involve systemic treatments or oral medications, but HT-001 targets the affected area directly, which may reduce the risk of systemic side effects. Researchers are excited about HT-001 because it has the potential to deliver faster relief with its localized action, setting it apart from existing solutions.

What evidence suggests that HT-001 could be an effective treatment for skin side effects from cancer therapy?

Research has shown that HT-001 Topical Gel effectively treats skin problems caused by certain cancer treatments known as EGFR inhibitors. In this trial, participants in the randomized, double-blind cohort will receive either HT-001 at varying concentrations (2%, 1%, or 0.5%) or a placebo. An earlier study demonstrated that all patients using HT-001 experienced noticeable skin improvements within six weeks, including reduced rash, pain, and itching. The gel successfully met at least one treatment goal for every patient. These findings suggest that HT-001 could be a helpful option for managing these uncomfortable side effects. ^{1 2 5 6 7}

Who Is on the Research Team?

Mario Lacouture, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 with cancer, who are starting EGFRI treatment within 4 weeks and have developed a rash or symptoms of it. They must be able to consent, attend visits, expect to live at least 3 months, follow contraceptive rules, and have an ECOG status of 0-2. Excluded are those with less than 8-week EGFRI therapy plan, recent radiation to head/neck/trunk, active infections or uncontrolled diseases that could affect the study's outcome.

Inclusion Criteria

I can and will attend all required visits, both in person and via telehealth.

Predicted life expectancy ≥ 3 months

I am an adult prescribed an EGFRI for my cancer treatment.

Exclusion Criteria

Patient has a history of hypersensitivity to aprepitant or any component of HT-001

Patient has a history of other skin disorders (eg, atopic dermatitis, psoriasis, recurrent skin infections) or history of illness that, in the opinion of the Investigator, would confound results of the study or pose unwarranted risk in administering study drug to the patient

Patient has abnormal laboratory values at Screening/Baseline (V1): Absolute neutrophil count < 1000/mm3 and WBC count < 3000/mm3, Platelet count < 50,000/mm3, AST > 2.5 × ULN, ALT > 2.5 × ULN, Bilirubin > 1.5 × ULN, Creatinine > 1.5 × ULN

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Treatment

Participants receive HT-001 2% Gel to measure pharmacokinetics

6 weeks

Daily application

Randomized Treatment

Participants are randomized to receive one of three concentrations of HT-001 or placebo

6 weeks

Daily application

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• HT-001
• HT-001 Placebo

Trial Overview The trial tests HT-001 Topical Gel in various concentrations (0.5%, 1%, and 2%) against a placebo for treating skin toxicities caused by EGFR inhibitors in cancer patients. It has two phases: an open-label phase where all receive HT-001 and a blinded phase where participants get either the gel or placebo randomly.

How Is the Trial Designed?

Group I: Open-Label PK Cohort Experimental Treatment 1 Intervention

Topical treatment with HT-001 2% Gel unblinded.

Group II: Randomized, Double Blind Cohort Placebo Group 4 Interventions

Topical treatment with HT-001 (2%, 1%, or 0.5%) or placebo (HT-001 vehicle), blinded

Who Is Running the Clinical Trial?

Hoth Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

180+

ICON Clinical Research

Industry Sponsor

Trials

52

Recruited

15,100+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Published Research Related to This Trial

Nanogel creams containing paclitaxel (PTX) and temozolomide (TMZ) were developed for topical melanoma treatment, showing improved drug penetration through rodent skin compared to traditional formulations.

In vitro studies demonstrated that the combination of PTX and TMZ was synergistically effective against melanoma cells, and preliminary in vivo results indicated a trend towards reduced tumor volume in mice treated with the nanogel creams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Cream Carrying Drug-Loaded Nanogels for Melanoma Treatment. Rahman, S., Haque, TN., Sugandhi, VV., et al.[2023]

In a clinical trial involving 30 breast cancer patients undergoing radiotherapy, a new hyaluronan (HA) formulation did not show significant differences in preventing skin toxicity compared to a placebo, as evaluated by physicians at week 5 during treatment and week 2 post-treatment.

While some patients preferred the HA formulation for skin appearance, this preference was not statistically significant, indicating that the HA cream may not provide substantial radioprotective benefits overall, except potentially for patients with larger breasts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel hyaluronan formulation for preventing acute skin reactions in breast during radiotherapy: a randomized clinical trial. Rahimi, A., Mohamad, O., Albuquerque, K., et al.[2020]

A case of radiation recall dermatitis (RRD) occurred in a 65-year-old man one year after receiving radiotherapy for head and neck cancer, linked to the use of hypericin (St. John's wort) during and after treatment.

The patient's skin reactions intensified during radiotherapy and recurred months later, highlighting the potential for certain drugs, like hypericin, to increase skin toxicity from radiotherapy, which emphasizes the need for healthcare providers to inquire about all medications, including alternative therapies, that patients may be taking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy -- case report and review of literature. Putnik, K., Stadler, P., Schäfer, C., et al.[2021]

The study developed a novel nanoemulgel formulation of chrysin, a flavonoid with anti-cancer properties, which significantly enhances the delivery and absorption of the drug through the skin, showing a mean droplet size of 156.9 nm and improved percutaneous absorption in ex vivo tests.

In vitro tests demonstrated that this formulation effectively reduced the required dose to achieve therapeutic effects on melanoma cell lines, while biocompatibility testing confirmed its safety for use, indicating it could be a promising treatment for localized skin cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Nanoemulgel for the Treatment of Skin Cancer: Proof-of-Technology. Nagaraja, S., Basavarajappa, GM., Attimarad, M., et al.[2021]

Acute skin toxicity affects 70%-100% of breast cancer patients undergoing radiation therapy, but the impact on their daily lives is complex and goes beyond just visible skin changes.

Interviews with seven women revealed that their experiences of skin reactions are intertwined with psychological aspects and the need for better information and support, highlighting the importance of a holistic approach to patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Women's experience of acute skin toxicity following radiation therapy in breast cancer. Andersen, ER., Eilertsen, G., Myklebust, AM., et al.[2022]

Citations

1. prnewswire.com prnewswire.com/news-releases/hoth-therapeutics-ht-001-interim-results-first-in-class-topical-therapy-preserves-cancer-treatment-while-resolving-dermatologic-side-effects-302489805.html

Hoth Therapeutics HT-001 Interim Results First-in-Class ... Hoth Therapeutics' HT-001 achieves 100% response rate in at least one endpoint in Phase 2a trial in PK patients for EGFR inhibitor-related skin toxicities.

2. cancernetwork.com cancernetwork.com/view/topical-gel-significantly-improves-egfr-inhibitor-related-skin-toxicity

Topical Gel Significantly Improves EGFR Inhibitor-Related ... All patients who received HT-001 in the phase 2a CLEER-001 trial showed significant skin toxicity improvements by 6 weeks.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05639933

NCT05639933 | Study to Investigate the Efficacy, Safety, ... The goal of this clinical trial is to learn about HT-001 Topical Gel for treatment of EGFR inhibitor-induced skin toxicities. The main questions it aims to ...

4. curetoday.com curetoday.com/view/ht-001-addresses-skin-toxicities-in-patients-with-cancer

HT-001 Addresses Skin Toxicities in Patients With Cancer Data outcomes showed a significant skin toxicity improvement by the six-week mark, demonstrating remarkable success, according to the press ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02874

Study to Investigate the Efficacy, Safety, and Tolerability of ... The goal of this clinical trial is to learn about HT-001 Topical Gel for treatment of EGFR inhibitor-induced skin toxicities.

6. healio.com healio.com/news/dermatology/20250112/topical-gel-shows-promise-in-treating-cutaneous-events-from-egfr-inhibitor-cancer-therapy

Topical gel shows promise in treating cutaneous events ... A novel topical gel, HT-001, has shown potential as a treatment for cutaneous side effects from epidermal growth factor receptor inhibitor cancer therapy.

7. firstwordpharma.com firstwordpharma.com/story/5975794

Hoth Therapeutics HT-001 Interim Results First-in-Class ... Hoth Therapeutics' HT-001 achieves 100% response rate in at least one endpoint in Phase 2a trial in PK patients for EGFR inhibitor-related skin toxicities.