APREPITANT for Skin Toxicities Associated with Epidermal Growth Factor Receptor Inhibitors | Acneiform eruption

Inclusion criteria

• {"criterion_text":"- 1. 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).\n- 2. 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.\n- 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n- 4. Predicted life expectancy ≥ 3 months.\n- 5. Participant is able and willing to comply with contraceptive requirements.\n- 6. Participant must have the ability and willingness to attend the necessary visits (telehealth and in person).\n- 7. 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."}

Exclusion criteria

• {"criterion_text":"- 1. 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.\n- 10.Participant has received non-stable escalating doses of topical antibiotics, topical steroids, or other topical treatments within 14 days prior to Screening/Baseline (V1). Prticipants 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.\n- 11.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.\n- 12.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.\n- 13.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).\n- 14.Participant t has a history of hypersensitivity to aprepitant (also present in CT.GOV) or any component of HT-001.\n- 15.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.\n- 2. 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.\n- 3. 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.\n- 4. 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\n- 5. Participant has a known history of QT interval prolongation\n- 6. 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).\n- 7.Participant has received aprepitant or other neurokinin-1 receptor antagonist within 4 weeks prior to Screening/Baseline (V1).\n- 8.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.\n- 9.Participant 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 participant."}

Primary endpoints

• {"endpoint_text":"- Part 1 (open-label PK cohort) • Investigating PK parameters including: measured drug concentrations above the lower limit of quantitation, number of participants with measurable systemic exposure; if data allow - area under the curve (AUC), maximum (or peak) concentration (Cmax), and time of peak concentration (Tmax)","definition_or_measurement_approach":"Pharmacokinetic (PK) assessment: measured drug concentrations above the lower limit of quantitation; number of participants with measurable systemic exposure; if data allow, calculate AUC, Cmax, and Tmax."}
• {"endpoint_text":"- Part 2 (randomized double-blind cohort) • Proportion of participants with a grade ≤ 1 based on the ARIGA scale after 6 weeks of HT-001 treatment","definition_or_measurement_approach":"Clinical efficacy measured by the Acneiform Rash Investigator’s Global Assessment (ARIGA) scale at 6 weeks; primary outcome is proportion with ARIGA grade ≤1."}

Secondary endpoints

• {"endpoint_text":"- • Change from Baseline in pruritus numeric rating scale (NRS; average itch and worst itch) after 3 weeks and 6 weeks of HT-001 treatment compared to placebo","definition_or_measurement_approach":"Patient-reported pruritus measured by Numeric Rating Scale (NRS) for average and worst itch at 3 and 6 weeks versus baseline and compared to placebo."}
• {"endpoint_text":"- • Change from Baseline in pain based on an NRS after 3 weeks and 6 weeks of HT-001 treatment compared to placebo","definition_or_measurement_approach":"Patient-reported pain measured by Numeric Rating Scale at 3 and 6 weeks versus baseline and compared to placebo."}
• {"endpoint_text":"- • Change from Baseline in acneiform rash grade based on the ARIGA scale at 3 weeks and 6 weeks of HT-001 treatment compared to placebo","definition_or_measurement_approach":"ARIGA scale assessment at 3 and 6 weeks compared to baseline and placebo."}
• {"endpoint_text":"- • Time to improvement for at least 1 grade using the ARIGA scale for acneiform rash for HT-001 treatment compared to placebo","definition_or_measurement_approach":"Time-to-event analysis measuring days to at least 1 grade improvement on ARIGA scale compared between HT-001 and placebo."}
• {"endpoint_text":"- • Time to topical rescue therapy treatment after initiation of HT-001 treatment compared to placebo","definition_or_measurement_approach":"Time from treatment initiation to first use of topical rescue therapy; comparison between HT-001 and placebo arms."}
• {"endpoint_text":"- • Proportion of patients with EGFRI dose reduction or discontinuation due to EGFR inhibitor skin toxicities after 6 weeks of HT-001 treatment compared to placebo","definition_or_measurement_approach":"Proportion of participants requiring EGFRI dose reduction or discontinuation for skin toxicities by week 6; comparison between arms."}
• {"endpoint_text":"- • Safety and tolerability of HT-001 as measured by: o Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)","definition_or_measurement_approach":"Safety assessed by incidence and severity of TEAEs and SAEs reported during study treatment and follow-up."}
• {"endpoint_text":"- • Safety and tolerability of HT-001 as measured by: o Skin irritation, as assessed using the modified Draize Scale to evaluate cutaneous signs of erythema and edema","definition_or_measurement_approach":"Skin irritation assessed with the modified Draize Scale evaluating erythema and edema."}
• {"endpoint_text":"- • Safety and tolerability of HT-001 as measured by: o Physical examinations","definition_or_measurement_approach":"Physical examinations documented per schedule to monitor safety."}
• {"endpoint_text":"- • Safety and tolerability of HT-001 as measured by: o Vital signs","definition_or_measurement_approach":"Routine vital signs monitoring per protocol schedule to assess safety."}
• {"endpoint_text":"- • Safety and tolerability of HT-001 as measured by: o 12-lead electrocardiograms (ECG)","definition_or_measurement_approach":"12-lead ECGs performed per schedule to monitor cardiac safety."}
• {"endpoint_text":"- • Safety and tolerability of HT-001 as measured by: o Clinical laboratory values (hematology, chemistry, urinalysis), including transaminase and bilirubin levels","definition_or_measurement_approach":"Clinical laboratory monitoring (hematology, chemistry, urinalysis) including liver function tests and bilirubin as safety endpoints."}

Methods

• Spain: Recruitment procedure and patient-facing materials (K1_ES_Recruitment Procedure; K2_ES_Recruitment Material_Flyer_Spanish; K2_ES_Recruitment Material_Brochure_Spanish) — patient-targeted flyers and brochures.
• Poland: Recruitment procedure and patient-facing materials (K1_PL_Recruitment Procedure_Polish; K2_PL_Recruitment Material_Patient Brochure_Polish; K2_PL_Recruitment Material_Flyer_Polish) — patient-targeted brochure and flyer materials.
• Hungary: Recruitment procedure and patient-facing materials (K1_HU_Recruitment Procedure; K2_HU_Recruitment Material_Flyer_Hungarian; K2_HU_Recruitment Material_Brochure_Hungarian) — patient-targeted flyer and brochure materials.
• Target audience across materials: patients receiving EGFR inhibitor therapy who develop acneiform/EGFRI-associated skin toxicities.

Spain

Earliest CTIS Part Ii Submission Date

13-11-2025

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

172

Number Of Sites

11

Number Of Participants

39

Poland

Earliest CTIS Part Ii Submission Date

27-11-2025

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

165

Number Of Sites

9

Number Of Participants

35

Hungary

Earliest CTIS Part Ii Submission Date

27-11-2025

Latest Decision Or Authorization Date

06-05-2026

Processing Time Days

160

Number Of Sites

3

Number Of Participants

24

Primary sponsor

Full Name

Hoth Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

sponsorDuties codes: 1, 12, 13, 2, 5, 6, 8 (various trial management/regulatory activities per entry)

Name

Premier Research International LLC

Responsibilities

PK analysis

Name

Northeast Bioanalytical Laboratories LLC

Responsibilities

PK processing

Name

Eurofins Central Laboratory B.V.

Responsibilities

Central laboratory functions (sponsorDuties code 4)

Name

Nuvisan France S.A.R.L.

Responsibilities

sponsorDuties code 14

Name

Merative US LP

Responsibilities

sponsorDuties codes: 3, 7

Third parties

• {"country":"France","full_name":"Nuvisan France S.A.R.L.","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Merative US LP","duties_or_roles":"sponsorDuties codes: 3, 7","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: 1, 12, 13, 2, 5, 6, 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Premier Research International LLC","duties_or_roles":"PK analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Northeast Bioanalytical Laboratories LLC","duties_or_roles":"PK processing","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"sponsorDuties codes: 4 (central laboratory)","organisation_type":"Pharmaceutical company"}