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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)

Primary Purpose

Acneiform Eruption Due to Chemical, Xerosis Cutis, Paronychia

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
HT-001 2% Topical Gel
HT-001 1% Topical Gel
HT-001 0.5% Topical Gel
HT-001 Placebo
Sponsored by
Hoth Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Acneiform Eruption Due to Chemical focused on measuring Acneiform rash, EGFR inhibitor, Cutaneous toxicities

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Adult patient (ie, ≥ 18 years of age at Screening [V1]) prescribed an approved EGFRI to treat cancer (indication within the approved labeling for the EGFRI) and is expected to begin EGFRI treatment within < 4 weeks of Screening (V1). Patient has developed a rash or symptoms of a rash (papular and/or pustular eruptions) or symptoms of a rash (cutaneous burning), at Baseline (V2), as assessed by both the Common Terminology Criteria for Adverse Events (CTCAE) grading and Acneiform rash IGA scales (ARIGA) (severity ≤ 3) with overall involvement ≤ 30% BSA. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Predicted life expectancy ≥ 3 months. Patient is able and willing to comply with contraceptive requirements. Patient must have the ability and willingness to attend the necessary visits (telehealth and in person). 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: Patient has severe cutaneous toxicity (severity = 4 on the CTCAE grading and Acneiform rash IGA 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. Subject has a presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the patient will comply with the protocol or complete the study per protocol. Patient has a history of other skin disorders (eg, atopic dermatitis, psoriasis, recurrent skin infections) and presence of active dermatological symptoms at the time of screening (prior to initiation of EGFRI therapy), 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. Patient has abnormal laboratory values at Screening (V1): Absolute neutrophil count < 1000/mm3 and white blood cell (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 Patient has a prescribed EGFRI therapy treatment plan that is less than 8 weeks total duration. 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 (V1). Patient has received neurokinin-1 receptor antagonist within 4 weeks prior to Screening (V1). Patient has had prior treatment with an investigational drug within 4 weeks prior to Screening (V1), or at least 8 half-lives of the drug, whichever is longer. Subject 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. Patient has received topical antibiotics, topical steroids, or other topical treatments (non-medicated emollients are allowed up until 1 day prior to V2) within 14 days to Baseline (V2). Patient has used systemic steroids within 14 days prior to Screening (V1) except for 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 determined by the study Investigator. Use of steroid inhalers and nasal corticosteroids is allowed. Patient has received treatment with a systemic antibiotic within 7 days prior to Screening (V1) (unless minocycline/doxycycline administered for CTCAE grade 3 acneiform rash). Patient has received concomitant treatment with pimozide, moderate to strong CYP3A4 inhibitors (diltiazem, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir), or strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin) with 30 days of Day 1 of treatment (V2). Patient has a history of hypersensitivity to any component of HT-001 (to be confirmed at Screening [V1] with patch testing). Patient is pregnant or lactating at Screening (V1) or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.

Sites / Locations

  • University of Miami
  • Washington University in St Louis School of MedicineRecruiting
  • MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Open-Label PK Cohort

Randomized, Double Blind Cohort

Arm Description

Topical treatment with HT-001 2% Gel unblinded.

Topical treatment with HT-001 (2%, 1%, or 0.5%) or placebo (HT-001 vehicle), blinded

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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
Time to rescue therapy
Time to topical rescue therapy treatment after initiation of HT-001
EGFR Inhibitor dose reduction or discontinuation
Proportion of patients with EGFRI dose reduction or discontinuation during the 6-week treatment period
Safety and tolerability of HT-001
Incidence of treatment-emergent adverse events and treatment-emergent serious adverse events
Modified Draize Scale
Assessment of skin irritation through measurement of cutaneous signs of erythema (score 0-3; 3 is most severe) and edema (add 0.5 if present)
Physical Examination
full physical examination will include examination of general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, heart, lungs, abdomen, lymph nodes, extremities, and nervous system. An AE form must be completed for all changes identified as clinically noteworthy.
Height
Height recorded in inches
Body weight
Body weight in pounds.

Full Information

First Posted
November 14, 2022
Last Updated
September 8, 2023
Sponsor
Hoth Therapeutics, Inc.
Collaborators
Worldwide Clinical Trials
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1. Study Identification

Unique Protocol Identification Number
NCT05639933
Brief Title
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
Acronym
CLEER
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 19, 2023 (Actual)
Primary Completion Date
December 30, 2024 (Anticipated)
Study Completion Date
January 29, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoth Therapeutics, Inc.
Collaborators
Worldwide Clinical Trials

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acneiform Eruption Due to Chemical, Xerosis Cutis, Paronychia
Keywords
Acneiform rash, EGFR inhibitor, Cutaneous toxicities

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
152 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Open-Label PK Cohort
Arm Type
Experimental
Arm Description
Topical treatment with HT-001 2% Gel unblinded.
Arm Title
Randomized, Double Blind Cohort
Arm Type
Placebo Comparator
Arm Description
Topical treatment with HT-001 (2%, 1%, or 0.5%) or placebo (HT-001 vehicle), blinded
Intervention Type
Drug
Intervention Name(s)
HT-001 2% Topical Gel
Intervention Description
Topical gel, 2% active
Intervention Type
Drug
Intervention Name(s)
HT-001 1% Topical Gel
Intervention Description
Topical gel, 1% active
Intervention Type
Drug
Intervention Name(s)
HT-001 0.5% Topical Gel
Intervention Description
Topical gel, 0.5% active
Intervention Type
Drug
Intervention Name(s)
HT-001 Placebo
Intervention Description
Topical gel, vehicle gel
Primary Outcome Measure Information:
Title
Acneiform Rash Investigator's Global Assessment Scale [ARIGA ]
Description
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
Time Frame
6 weeks
Title
Pharmacokinetics of HT-001 applied topically [Cohort 1] - Area Under the Curve (AUC)
Description
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)
Time Frame
Day 1 and Day 42
Title
Pharmacokinetics of HT-001 applied topically [Cohort 1] - Peak Plasma Concentration (Cmax)
Description
Characterize pharmacokinetics of HT-001 parameters including: maximum (or peak) serum concentration (Cmax)
Time Frame
Day 1 and Day 42
Secondary Outcome Measure Information:
Title
Pruritus Numeric Rating Scale (NRS)
Description
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").
Time Frame
3 weeks and 6 weeks
Title
Pain Numeric Rating Scale
Description
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")
Time Frame
3 weeks and 6 weeks
Title
Change in acneiform rash severity
Description
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 Frame
3 weeks and 6 weeks
Title
Time to improvement
Description
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
Time Frame
6 weeks Day 1- Day 42
Title
Time to rescue therapy
Description
Time to topical rescue therapy treatment after initiation of HT-001
Time Frame
Treatment Day 1- Day 42
Title
EGFR Inhibitor dose reduction or discontinuation
Description
Proportion of patients with EGFRI dose reduction or discontinuation during the 6-week treatment period
Time Frame
Treatment Day 1- Day 42
Title
Safety and tolerability of HT-001
Description
Incidence of treatment-emergent adverse events and treatment-emergent serious adverse events
Time Frame
screening, Day 1 - 42, follow-up (Day 56)
Title
Modified Draize Scale
Description
Assessment of skin irritation through measurement of cutaneous signs of erythema (score 0-3; 3 is most severe) and edema (add 0.5 if present)
Time Frame
Day 1, 7, 21, 35, 42, 56
Title
Physical Examination
Description
full physical examination will include examination of general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, heart, lungs, abdomen, lymph nodes, extremities, and nervous system. An AE form must be completed for all changes identified as clinically noteworthy.
Time Frame
Day 1, 7, 21, 35, 42, 56
Title
Height
Description
Height recorded in inches
Time Frame
Screening
Title
Body weight
Description
Body weight in pounds.
Time Frame
Day 1, 21, 42, 56
Other Pre-specified Outcome Measures:
Title
Scoring system for paronychia related to oncologic treatments (SPOT)
Description
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).
Time Frame
Day 1, 7, 21, 35, 42
Title
Xerosis Severity Scale
Description
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
Time Frame
Day 1, 7, 21, 35, 42
Title
Change in Quality of Life (QoL)
Description
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
Time Frame
Day 1, 21, 42
Title
Progression-Free survival
Description
Progression-free survival through the follow-up period
Time Frame
8 weeks (Day 1 - 56)
Title
Overall Survival
Description
Overall Survival through the follow-up period
Time Frame
8 weeks (Day 1 - 56)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patient (ie, ≥ 18 years of age at Screening [V1]) prescribed an approved EGFRI to treat cancer (indication within the approved labeling for the EGFRI) and is expected to begin EGFRI treatment within < 4 weeks of Screening (V1). Patient has developed a rash or symptoms of a rash (papular and/or pustular eruptions) or symptoms of a rash (cutaneous burning), at Baseline (V2), as assessed by both the Common Terminology Criteria for Adverse Events (CTCAE) grading and Acneiform rash IGA scales (ARIGA) (severity ≤ 3) with overall involvement ≤ 30% BSA. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Predicted life expectancy ≥ 3 months. Patient is able and willing to comply with contraceptive requirements. Patient must have the ability and willingness to attend the necessary visits (telehealth and in person). 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: Patient has severe cutaneous toxicity (severity = 4 on the CTCAE grading and Acneiform rash IGA 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. Subject has a presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the patient will comply with the protocol or complete the study per protocol. Patient has a history of other skin disorders (eg, atopic dermatitis, psoriasis, recurrent skin infections) and presence of active dermatological symptoms at the time of screening (prior to initiation of EGFRI therapy), 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. Patient has abnormal laboratory values at Screening (V1): Absolute neutrophil count < 1000/mm3 and white blood cell (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 Patient has a prescribed EGFRI therapy treatment plan that is less than 8 weeks total duration. 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 (V1). Patient has received neurokinin-1 receptor antagonist within 4 weeks prior to Screening (V1). Patient has had prior treatment with an investigational drug within 4 weeks prior to Screening (V1), or at least 8 half-lives of the drug, whichever is longer. Subject 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. Patient has received topical antibiotics, topical steroids, or other topical treatments (non-medicated emollients are allowed up until 1 day prior to V2) within 14 days to Baseline (V2). Patient has used systemic steroids within 14 days prior to Screening (V1) except for 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 determined by the study Investigator. Use of steroid inhalers and nasal corticosteroids is allowed. Patient has received treatment with a systemic antibiotic within 7 days prior to Screening (V1) (unless minocycline/doxycycline administered for CTCAE grade 3 acneiform rash). Patient has received concomitant treatment with pimozide, moderate to strong CYP3A4 inhibitors (diltiazem, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir), or strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin) with 30 days of Day 1 of treatment (V2). Patient has a history of hypersensitivity to any component of HT-001 (to be confirmed at Screening [V1] with patch testing). Patient is pregnant or lactating at Screening (V1) or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hayley Springer
Phone
646-756-2997
Email
hayley@hoththerapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mario Lacouture, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aliette Espinosa
Phone
305-689-3376
First Name & Middle Initial & Last Name & Degree
Robert Kirsner, MD
Facility Name
Washington University in St Louis School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mary Tabacchi
First Name & Middle Initial & Last Name & Degree
Stephanie Farris
First Name & Middle Initial & Last Name & Degree
Milan Anandkat, MD
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stacie Stutt
Phone
713-794-1918
Email
SNStutte@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Anisha Patel, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22417992
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.
Results Reference
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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

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