Clinical trial NCT05639933: 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
Official title: A Randomized, Placebo-controlled, Parallel Phase 2a Dose-ranging 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acneiform Eruption Due to Chemical
Xerosis Cutis
Paronychia
Keywords: Acneiform rash
EGFR inhibitor
Cutaneous toxicities
Lead sponsor: Hoth Therapeutics, Inc.
Sponsor class: OTHER
Collaborators: name: Worldwide Clinical Trials
First posted: 2022-12-07
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Detailed description: This is a randomized, double-blind, placebo-controlled, multi-center Phase 2a dose-ranging study to evaluate the efficacy, safety, and tolerability of HT-001 for treatment of EGFRI-induced skin toxicity. The study will include adult patients (≥ 18 years of age) scheduled to receive initial or repeat EGFRI therapy.

The study will be conducted in 2 periods: Part 1, an open-label cohort consisting of 12 patients to measure pharmacokinetics of HT 001 gel followed by Part 2, a randomized, parallel arm study comparing 3 dose strengths of HT-001 gel to placebo (HT 001 vehicle). Patients in the randomized cohorts will be randomly assigned to 1 of the 4 treatment arms in a 2:2:2:1 ratio (active groups = 2: placebo = 1).

All patients in both open-label and blinded cohorts will apply the study drug once a day to each area affected with cutaneous toxicity up to 30% body surface area (BSA) involvement, inclusive of skin, scalp, and nails.

The goal of the study is to determine the minimum efficacious dose strength(s) for further investigation. The dose effect, together with the application site safety assessments, and therapeutic effects based on the primary and secondary endpoints will be evaluated.

Eligibility criteria: Inclusion Criteria:

1. Adult patient (ie, ≥ 18 years of age at Screening/Baseline \[V1\]) prescribed an approved EGFRI to treat cancer (indication within the approved labeling for the EGFRI).
2. Patient has developed a rash or symptoms of a rash (papular and/or pustular eruptions) or symptoms of a rash (cutaneous burning), as assessed by both Common Terminology Criteria for Adverse Events (CTCAE) grading and ARIGA scales (severity

   ≤ 3) with overall involvement ≤ 30% BSA.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
4. Predicted life expectancy ≥ 3 months.
5. Patient is able and willing to comply with contraceptive requirements.
6. Patient must have the ability and willingness to attend the necessary visits (telehealth and in person).
7. Patient 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.

Exclusion Criteria:

1. Patient 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.
2. Patient has any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the patient would comply with the protocol or complete the study per protocol.
3. 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.
4. Patient has abnormal laboratory values at Screening/Baseline (V1):

   1. Absolute neutrophil count \< 1000/mm3 and WBC count \< 3000/mm3
   2. Platelet count \< 50,000/mm3
   3. Aspartate transaminase (AST) \> 2.5 × upper limit of normal (ULN)
   4. Alanine transaminase (ALT) \> 2.5 × ULN
   5. Bilirubin \> 1.5 × ULN
   6. Creatinine \> 1.5 × ULN
5. Patient 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).
6. Patient has received aprepitant or other neurokinin-1 receptor antagonist within 4 weeks prior to Screening/Baseline (V1).
7. Patient 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.
8. Patient has an active infection (eg, pneumonia) 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 patient.
9. Patient has received non-stable escalating doses of topical antibiotics, topical steroids, or other topical treatments within 14 days prior to Screening/Baseline (V1). Patients who have been on stable doses of topical antibiotics, topical steroids, or other topical treatments for 14 days or more are allowed to be enrolled and to stay on their current prescription. Reduction in dose due to improvement in EGFRI-related toxicities is allowed.
10. Patient has used non-stable escalating doses of systemic steroids within 14 days prior to Screening/Baseline (V1) excluding low-dose systemic corticosteroids as part of standard of care for prevention or treatment of chemotherapy-induced nausea and vomiting; acceptability of the steroid and dose is to be determined by the study Investigator. Patients who have been on a stable dose of systemic steroids for 14 days or more are allowed to be enrolled and to stay on their current prescription. Reduction in dose due to improvement in EGFRI-related toxicities is allowed. Use of steroid inhalers and nasal corticosteroids is allowed.
11. Patient has received non-stable escalating dose treatment with a systemic antibiotic within 14 days prior to Screening/Baseline (V1). Patients who have been on stable doses of systemic antibiotics for 14 days or more are allowed to be enrolled and to stay on their current prescription. Reduction in dose due to improvement in EGFRI-related toxicities is allowed.
12. Patient has received concomitant treatment with pimozide, moderate to strong cytochrome p450 (CYP) 3A4 inhibitors (diltiazem, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir), or strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin) within 30 days of Screening/Baseline (V1).
13. Patient has a history of hypersensitivity to aprepitant or any component of HT-001.
14. Patient is pregnant or lactating at Screening/Baseline (V1) or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.

Primary outcomes:
measure: Acneiform Rash Investigator's Global Assessment Scale [ARIGA ]
timeFrame: 6 weeks
measure: Pharmacokinetics of HT-001 applied topically [Cohort 1] - Area Under the Curve (AUC)
timeFrame: Day 1 and Day 42
measure: Pharmacokinetics of HT-001 applied topically [Cohort 1] - Peak Plasma Concentration (Cmax)
timeFrame: Day 1 and Day 42
Secondary outcomes:
measure: Pruritus Numeric Rating Scale (NRS)
timeFrame: 3 weeks and 6 weeks
measure: Pain Numeric Rating Scale
timeFrame: 3 weeks and 6 weeks
measure: Change in acneiform rash severity
timeFrame: 3 weeks and 6 weeks
measure: Time to improvement
timeFrame: 6 weeks Day 1- Day 42
measure: Time to rescue therapy
timeFrame: Treatment Day 1- Day 42
measure: EGFR Inhibitor dose reduction or discontinuation
timeFrame: Treatment Day 1- Day 42
measure: Safety and tolerability of HT-001
timeFrame: screening, Day 1 - 42, follow-up (Day 56)
measure: Modified Draize Scale
timeFrame: Day 1, 7, 21, 35, 42, 56
measure: Physical Examination
timeFrame: Day 1, 7, 21, 35, 42, 56
measure: Height
timeFrame: Screening
measure: Body weight
timeFrame: Day 1, 21, 42, 56
Other outcomes:
measure: Scoring system for paronychia related to oncologic treatments (SPOT)
timeFrame: Day 1, 7, 21, 35, 42
measure: Xerosis Severity Scale
timeFrame: Day 1, 7, 21, 35, 42
measure: Change in Quality of Life (QoL)
timeFrame: Day 1, 21, 42
Locations:
city: Irvine
country: United States
facility: UCI Health - CIACC
state: California
city: Orange
country: United States
facility: UC Irvine - Chao Family Cancer Center
state: California
city: Washington
country: United States
facility: The George Washington University Medical Faculty Associates
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University in St Louis School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Mineola
country: United States
facility: NYU Langone Health
state: New York
city: New Hyde Park
country: United States
facility: Northwell Physician Partners Dermatology
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: NYU Langone Health
name: Mario Lacouture, MD
role: STUDY_CHAIR
References:
citation: 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.