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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат HT-001 2% Topical Gel
  Topical gel, 2% active
• Препарат HT-001 1% Topical Gel
  Topical gel, 1% active
• Препарат HT-001 0.5% Topical Gel
  Topical gel, 0.5% active
• Препарат HT-001 Placebo
  Topical gel, vehicle gel

Первичные конечные точки

• Acneiform Rash Investigator's Global Assessment Scale [ARIGA ] [Срок оценки: 6 weeks]
• Pharmacokinetics of HT-001 applied topically [Cohort 1] - Area Under the Curve (AUC) [Срок оценки: Day 1 and Day 42]
• Pharmacokinetics of HT-001 applied topically [Cohort 1] - Peak Plasma Concentration (Cmax) [Срок оценки: Day 1 and Day 42]

Вторичные конечные точки (11)

• Pruritus Numeric Rating Scale (NRS) [Срок оценки: 3 weeks and 6 weeks]
• Pain Numeric Rating Scale [Срок оценки: 3 weeks and 6 weeks]
• Change in acneiform rash severity [Срок оценки: 3 weeks and 6 weeks]
• Time to improvement [Срок оценки: 6 weeks Day 1- Day 42]
• Time to rescue therapy [Срок оценки: Treatment Day 1- Day 42]
• EGFR Inhibitor dose reduction or discontinuation [Срок оценки: Treatment Day 1- Day 42]
• Safety and tolerability of HT-001 [Срок оценки: screening, Day 1 - 42, follow-up (Day 56)]
• Modified Draize Scale [Срок оценки: Day 1, 7, 21, 35, 42, 56]
• Physical Examination [Срок оценки: Day 1, 7, 21, 35, 42, 56]
• Height [Срок оценки: Screening]
• Body weight [Срок оценки: Day 1, 21, 42, 56]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• Participant has received non-stable escalating doses of topical antibiotics, topical steroids, or other topical treatments within 14 days prior to Screening/Baseline (V1). Participants 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.
• Participant 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 Investigator. Participants 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.
• Participant has received non-stable escalating dose treatment with a systemic antibiotic within 14 days prior to Screening/Baseline (V1). Participants 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.
• Participant 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).
• Participant has a history of hypersensitivity to aprepitant or any component of HT-001.
• Participant 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Поддерживающая терапия

Центры проведения

США · 9 центров

• UCI Health - CIACC — Irvine
• UC Irvine - Chao Family Cancer Center — Orange
• Regis Clinical Research — Miami
• Dana Farber Cancer Institute — Boston
• NYU Langone Health — Mineola
• Northwell Physician Partners Dermatology — New Hyde Park
• Montefiore Medical Center — The Bronx
• Gabrail Cancer & Research Center — Canton
• … и ещё 1 центр

Польша · 2 центра

• Centrum Medyczne Pratia Krakow — Krakow
• NZOZ Neuromed M. i M. Nastaj Sp.P — Lublin

Испания · 1 центр

• Hospital Sant Joan de Deu-Fundacio Althaia — Manresa

Публикации

• 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

Идентификаторы

NCT: NCT05639933 · CLEER-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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