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.
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.
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.
Absolute neutrophil count < 1000/mm3 and WBC count < 3000/mm3
Parallel
HT-001 2% Topical Gel
DrugTopical gel, 2% active
HT-001 1% Topical Gel
DrugTopical gel, 1% active
HT-001 0.5% Topical Gel
DrugTopical gel, 0.5% active
HT-001 Placebo
DrugTopical gel, vehicle gel
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
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)
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)
Pruritus Numeric Rating Scale (NRS)
Change from Baseline in Pruritus Numeric Rating Scale (average itch and worst itch); The numerical scale is ranked from 0 ("no itch") to 10 ("worst imaginable itch").
Pain Numeric Rating Scale
Change from Baseline in pain based on a 11-point NRS (where "0" indicates "no pain", "5" indicates "moderate pain" and "10" indicates "worst pain imaginable")
Change in acneiform rash severity
Change from Baseline in acneiform rash grade based on the Acneiform Rash Investigator's Global Assessment Scale \[ARIGA\]; novel 5-point scale 0-4 with score of 0 is clear and grade 4 being most severe
Time to improvement
Time to improvement in at least one grade using the Acneiform Rash Investigator's Global Assessment Scale \[ARIGA \] for acneiform rash; novel 5-point scale 0-4 with score of 0 is clear and grade 4 being most severe
Scoring system for paronychia related to oncologic treatments (SPOT)
Proportion of patients with improvement in paronychia based on the SPOT scale. Each parameter of paronychia, such as redness (R), edema (E), discharge (D) and granulation tissue (G), is evaluated on a 4-point scale from 0 to 3. The highest score for each R-E-D-G parameter among all involved fingers (or toes) of the respective hand (or foot) represents the overall score for that parameter on that hand (or foot) - note, the highest scores for the different parameters could originate from different fingers (or toes).
Xerosis Severity Scale
Proportion of patients with improvement in xerosis using the Xerosis Severity Scale adapted from Guenther et al. (Guenther et al., 2012). The assessment uses signs and symptoms of xerosis (such as rough/scaling skin, itching, pain, erythema, and fissures) as a composite score to determine the severity classification. In this scale, "-" indicates not present; "+"indicates a mild symptom; "++" indicates a moderate symptom; and "+++" indicates a severe symptom
Change in Quality of Life (QoL)
Change in quality of life based on FACT-EGFR-18. This 18-item QoL assessment was developed by Wagner et al. using a 5-point Likert scale (ie, 0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 4 = very much) with a recall period of the past 7 days
Click on the lead sponsor to view all of their trials.
Hoth Therapeutics, Inc.
Lead sponsor
ICON Clinical Research
Collaborator
