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 CLEER Trial (Chemotherapy Longevity by Evading EGFR Inhibitor Reactions)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hoth Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2026-01-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Hoth Therapeutics, Inc

External identifiers

EU CT number

2025-523058-16-00

ClinicalTrials.gov

NCT05639933

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Dose response, Efficacy, Safety

Part 1 (open-label pharmacokinetics [PK] cohort):
• To characterize HT-001 PK following topical application
Part 2 (randomized double-blind cohort):
• To evaluate the efficacy of HT-001 for treatment of participants undergoing epidermal growth factor inhibitor (EGFRI) therapy who develop acneiform rash using the acneiform rash investigator’s global assessment (ARIGA) scale

Secondary objectives 1

1. To evaluate other efficacy parameters related to acneiform rash during treatment with HT-001, such as pain and pruritus (also efficacy measured using the ARIGA scale for participants in Part 1) • To evaluate the impact of HT-001 on the frequency of dose reductions and discontinuations of EGFRI therapy • To evaluate the safety and tolerability of HT-001 in participants undergoing EGFRI therapy

Conditions and MedDRA coding

Skin Toxicities Associated with Epidermal Growth Factor Receptor Inhibitors

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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).
2. 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.
3. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
4. 4. Predicted life expectancy ≥ 3 months.
5. 5. Participant is able and willing to comply with contraceptive requirements.
6. 6. Participant must have the ability and willingness to attend the necessary visits (telehealth and in person).
7. 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 15

1. 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.
2. 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.
3. 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.
4. 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
5. 5.Participant has a known history of QT interval prolongation
6. 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).
7. 7.Participant has received aprepitant or other neurokinin-1 receptor antagonist within 4 weeks prior to Screening/Baseline (V1).
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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).
14. 14.Participant t has a history of hypersensitivity to aprepitant (also present in CT.GOV) or any component of HT-001.
15. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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)
2. 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

Secondary endpoints 12

1. • 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
2. • Change from Baseline in pain based on an NRS after 3 weeks and 6 weeks of HT-001 treatment compared to placebo
3. • 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
4. • Time to improvement for at least 1 grade using the ARIGA scale for acneiform rash for HT-001 treatment compared to placebo
5. • Time to topical rescue therapy treatment after initiation of HT-001 treatment compared to placebo
6. • 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
7. • Safety and tolerability of HT-001 as measured by: o Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)
8. • 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
9. • Safety and tolerability of HT-001 as measured by: o Physical examinations
10. • Safety and tolerability of HT-001 as measured by: o Vital signs
11. • Safety and tolerability of HT-001 as measured by: o 12-lead electrocardiograms (ECG)
12. • Safety and tolerability of HT-001 as measured by: o Clinical laboratory values (hematology, chemistry, urinalysis), including transaminase and bilirubin levels

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hoth Therapeutics Inc.

Sponsor organisation

Hoth Therapeutics Inc.

Address

1177 Avenue Of The Americas Floor 5th

City

New York

Postcode

10036-2714

Country

United States

Scientific contact point

Organisation

Hoth Therapeutics Inc.

Contact name

Hoth Scientific Advisory

Public contact point

Organisation

Hoth Therapeutics Inc.

Contact name

Hoth Scientific Advisory

Third parties 6

Locations

3 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications