Study to Investigate the Efficacy, Safety, and Tolerability of Topical HT-001 for the Treatment of Skin Toxicities Associated With Epidermal Growth Factor Receptor Inhibitors

NCT05639933 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CLEER-001
• Study Type: interventional
• Target: 152
• Locations: 3 countries
• Sites: 12

Brief Summary

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 answer are:

• Determine the therapeutic effect of HT-001 for treatment of patients who develop acneiform rash undergoing Epidermal Growth Factor inhibitor (EGFRI) therapy using the acneiform rash investigator's global assessment scale \[ARIGA\]
• Evaluate the safety of HT-001 during treatment Participants will apply HT-001 Gel once per day for 6 weeks, during which the effect on treating acneiform rash or other skin disorders induced by EGFRI therapy will be evaluated using different assessment tools to measure severity of rash, pain, and itching (pruritus), as well as the change in quality of life. The study will be completed in 2 periods: the first period is open-label (unblinded) and all patients will receive HT-001 topical gel with the active ingredient; the second period is blinded and patients will be randomized to receive one of three concentrations of HT-001 or placebo. Researchers will compare HT-001 to the placebo in the second period to see if HT-001 provides a significant treatment effect.

Conditions

Xerosis Cutis; Paronychia; Acneiform Eruption Due to Chemical

Keywords

Acneiform rash; EGFR inhibitor; Cutaneous toxicities

Outcome Measures

Primary Outcomes (3)

• Acneiform Rash Investigator's Global Assessment Scale [ARIGA ]

  Proportion of patients with a grade ≤ 1 based on the Acneiform Rash Investigator's Global Assessment \[ARIGA\] Scale; novel 5-point scale 0-4 with score of 0 is clear and grade 4 being most severe

  6 weeks

• Pharmacokinetics of HT-001 applied topically [Cohort 1] - Area Under the Curve (AUC)

  Characterize pharmacokinetics of HT-001 parameters including: measured drug concentrations above the lower limit of quantitation, number of patients with measurable systemic exposure; if data allow - area under the curve (AUC)

  Day 1 and Day 42

• Pharmacokinetics of HT-001 applied topically [Cohort 1] - Peak Plasma Concentration (Cmax)

  Characterize pharmacokinetics of HT-001 parameters including: maximum (or peak) serum concentration (Cmax)

  Day 1 and Day 42

Secondary Outcomes (11)

• Pruritus Numeric Rating Scale (NRS)

  3 weeks and 6 weeks

• Pain Numeric Rating Scale

  3 weeks and 6 weeks

• Change in acneiform rash severity

  3 weeks and 6 weeks

• Time to improvement

  6 weeks Day 1- Day 42

• Time to rescue therapy

  Treatment Day 1- Day 42

Other Outcomes (3)

• Scoring system for paronychia related to oncologic treatments (SPOT)

  Day 1, 7, 21, 35, 42

• Xerosis Severity Scale

  Day 1, 7, 21, 35, 42

• Change in Quality of Life (QoL)

  Day 1, 21, 42

Study Arms (2)

Open-Label PK Cohort

EXPERIMENTAL

Topical treatment with HT-001 2% Gel unblinded.

Drug: HT-001 2% Topical Gel

Randomized, Double Blind Cohort

PLACEBO COMPARATOR

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

Drug: HT-001 2% Topical Gel; Drug: HT-001 1% Topical Gel; Drug: HT-001 0.5% Topical Gel; Drug: HT-001 Placebo

Interventions

HT-001 2% Topical Gel DRUG

Topical gel, 2% active

Open-Label PK Cohort; Randomized, Double Blind Cohort

HT-001 1% Topical Gel DRUG

Topical gel, 1% active

Randomized, Double Blind Cohort

HT-001 0.5% Topical Gel DRUG

Topical gel, 0.5% active

Randomized, Double Blind Cohort

HT-001 Placebo DRUG

Topical gel, vehicle gel

Randomized, Double Blind Cohort

Eligibility Criteria

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

You may qualify if:

• Adult participant (ie, ≥ 18 years of age at Screening/Baseline \[V1\]) prescribed an approved EGFRI to treat cancer (indication within the approved labeling for the EGFRI and/or on National Comprehensive Cancer Network guidelines or equivalent local standards).
• Approved EGFRIs include, but are not limited to: gefitinib, erlotinib, osimertinib, lapatinib, afatinib, dacomitinib, neratinib, vandetanib, lazertinib, cetuximab, panitumumab, necitumumab, pertuzumab, and amivantamab-vmjw.
• Administration of an EGFRI, in combination with other drugs, for treatment of cancer is acceptable as long as the other drug is identified in the approved label of the EGFRI (eg, erlotinib with gemcitabine) or part of the NCCN guidelines or equivalent local standards.
• Participant has developed a rash or symptoms of a rash (papular and/or pustular eruptions or cutaneous burning), as assessed by both Common Terminology Criteria for Adverse Events (CTCAE) grading and ARIGA scales (severity ≤ 3) with overall involvement ≤ 30% BSA.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Predicted life expectancy ≥ 3 months.
• Participant is able and willing to comply with contraceptive requirements
• Participant must have the ability and willingness to attend the necessary visits (telehealth and in person).
• Participant must be willing and able to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.

You may not qualify if:

• Participant has severe cutaneous toxicity (severity = 4 on the CTCAE grading and ARIGA scales) or cutaneous toxicity involvement that is \> 30% BSA, or other severe systemic toxicity (severity \> 3 on the CTCAE v5.0 scale) as a result of EGFRI therapy.
• Participant has any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant would comply with the protocol or complete the study per protocol.
• Participant 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 participant.
• Participant has abnormal laboratory values at Screening/Baseline (V1):
• Absolute neutrophil count \< 1000/mm3 and WBC count \< 3000/mm3
• Platelet count \< 50,000/mm3
• Aspartate transaminase (AST) \> 2.5 × upper limit of normal (ULN)
• Alanine transaminase (ALT) \> 2.5 × ULN
• Bilirubin \> 1.5 × ULN
• Creatinine \> 1.5 × ULN
• Participant has a known history of QT interval prolongation.
• Participant has a prescribed cancer treatment plan that requires radiation treatment to the head, neck, or upper trunk concurrent with EGFRI therapy or has previously received radiation therapy within 4 weeks prior to Screening/Baseline (V1).
• Participant has received aprepitant or other neurokinin-1 receptor antagonist within 4 weeks prior to Screening/Baseline (V1).
• Participant has had prior treatment with an investigational drug within 4 weeks prior to Screening/Baseline (V1), or at least 8 half-lives of the drug, whichever is longer.
• Participant has an active infection (eg, pneumonia or pneumonitis) or any uncontrolled disease except for the malignancy that, in the opinion of the Investigator, might confound the result or the study or pose unwarranted risk in administering the study drug to the participant.

Sponsors & Collaborators

• Hoth Therapeutics, Inc.: lead
• ICON Clinical Research: collaborator

Study Sites (12)

UCI Health - CIACC

Irvine, California, 92612, United States

RECRUITING

UC Irvine - Chao Family Cancer Center

Orange, California, 92868, United States

RECRUITING

Regis Clinical Research

Miami, Florida, 33126, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

NYU Langone Health

Mineola, New York, 11501, United States

RECRUITING

Northwell Physician Partners Dermatology

New Hyde Park, New York, 11042, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

Gabrail Cancer & Research Center

Canton, Ohio, 44718, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Centrum Medyczne Pratia Krakow

Krakow, 30-727, Poland

ACTIVE NOT RECRUITING

NZOZ Neuromed M. i M. Nastaj Sp.P

Lublin, 20-064, Poland

ACTIVE NOT RECRUITING

Hospital Sant Joan de Deu-Fundacio Althaia

Manresa, 8243, Spain

ACTIVE NOT RECRUITING

Related Publications (1)

• Guenther L, Lynde CW, Andriessen A, Barankin B, Goldstein E, Skotnicki SP, Gupta SN, Choi KL, Rosen N, Shapiro L, Sloan K. Pathway to dry skin prevention and treatment. J Cutan Med Surg. 2012 Jan-Feb;16(1):23-31. doi: 10.1177/120347541201600106.

  PMID: 22417992 BACKGROUND

MeSH Terms

Conditions

Paronychia

Interventions

Gels

Condition Hierarchy (Ancestors)

Skin Diseases, Infectious; Infections; Nail Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Mario Lacouture, MD

  NYU Langone Health

  STUDY CHAIR

Central Study Contacts

Hayley Springer

CONTACT

866-239-7459; admin@hoththerapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2022
• First Posted: December 7, 2022
• Study Start: July 19, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); PL (2); ES (1)