Topically Applied AMTX-100 CF for Adult Patients With Mild to Moderate Atopic Dermatitis

A Two Part, Phase I/II, Multi-Center, Double-Blind, Randomized, Vehicle-Controlled Study of the Safety and Efficacy of Topically Applied AMTX-100 CF in Adult Patients With Mild to Moderate Atopic Dermatitis

This study determines the Maximum Tolerable Dose (MTD) by maximum BSA percentage treated and evaluates safety and efficacy of 1.1% w/w AMTX-100 CF versus placebo (vehicle).

The study has two parts:

Phase I (Part 1):

Approximately Twenty-five (25) subjects with various treatable Body Surface Area (BSA) involvement of Mild to Moderate Atopic Dermatitis will be enrolled in the study and treated with 1.1% w/w AMTX-100 CF.

Phase II (Part 2):

Approximately sixty (60) subjects with Mild to Moderate Atopic Dermatitis with various treatable BSA involvement of Mild to Moderate Atopic Dermatitis will be randomized to be treated with 1.1% w/w AMTX-100 CF3 concentration or Vehicle (Placebo) in the study.

AMTX-100 CF3 drug product is formulated as a water-based, topical cream incorporating a 28-amino acid synthetic polypeptide (AMTX-100) as the active pharmaceutical ingredient (API). AMTX-100 is a chimeric, cell-penetrating, bifunctional nuclear transport modifier (NTM), that is engineered to modulate nuclear transport of transcription factors (NF-κB, NFAT, AP-1, and STAT1) involved in the activation of gene expression of key mediators of inflammation (TNFα, IL-1β, IL-6, IL-17, MCP-1, etc.) and metabolic syndrome (ChREBP and SREBP) by importin α/β complex and importin β, respectively. This further leads to a reduction in pro-inflammatory cytokine/chemokine production and lipid and carbohydrate metabolic products.

AMTX-100 CF3 is intended to improve symptoms associated with mild to moderate Atopic Dermatitis in adults. This Phase I/II study aims to determine the Maximum Tolerable Dose (MTD) by maximum BSA percentage treated and to evaluate efficacy of 1.1% w/w AMTX-100 CF3 versus placebo (vehicle).

Part 1 Inclusion Criteria:

Subjects are required to meet ALL of the following criteria for enrollment into the Phase I (Part 1) of the study:

1. Male or female subjects who are 18 years or older

2. If female and not infertile (defined below), the subject must agree for the duration of the study to use one of the following forms of contraception 1) systemic hormonal treatment 2) an intrauterine device (IUD) which was implanted at least 2 months prior to screening or 3) "double-barrier" contraception (condom, diaphragm and spermicide are each considered a barrier). Females are considered to be infertile if they are either a) surgically sterile or b) have had spontaneous amenorrhea for at least the last 2 years and at least 2 years after the onset of amenorrhea while not receiving hormone replacement therapy and had a Follicle-Stimulating Hormone (FSH) level greater than 40 mIU/mL and an estradiol level less than 30 pg/mL

3. All fertile female subjects as described above need to have a negative urine pregnancy test at the screening and baseline visits

4. Subject is capable of providing informed consent and is willing to sign the ICF prior to study Screening and agrees to comply with the study protocol requirements

5. Subject is able to apply topical products on all treatable assigned areas by self and/or caregiver (if applicable), per the Investigator

6. Subject is in general good physical/mental health per the Investigator

7. Subject's Total Body Surface Area (BSA) is between 1.5 and 2.1 m2 per the Mosteller formula

8. The subject has physician confirmed mild to moderate Atopic Dermatitis (AD) defined by the Eichenfield revised criteria of Hannifin and Rajka, for at least 6 months prior to study enrollment

9. Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD™) score of 2 or 3 (mild to moderate) at the screening and baseline visits

10. Subject has Atopic Dermatitis (AD) involvement with eligible treatable percent of the BSA appropriate for topical treatment per the assigned cohort at the screening and baseline visits per below:

    1. Cohort 1: 3% BSA ≤ AD Affected Area ≤ 6% BSA
    2. Cohort 2: 6% BSA < AD Affected Area ≤ 12% BSA
    3. Cohort 3: 12% BSA < AD Affected Area ≤ 24% BSA
    4. Cohort 4: 24% BSA < AD Affected Area ≤ 48% BSA
    5. Cohort 5: 48% BSA < AD Affected Area ≤ 70% BSA

Note: Calculation of Treatable BSA percentage (% of the total BSA that is AD-involved, excluding the scalp, face, eyes, eyelids, neck, hands, palms, feet, groin, genitals or axillae) will be completed by the method below:

o "Handprint Method": the area represented by the palm with all five digits adducted together is approximately 1% of the subject's BSA

Part 1 Exclusion Criteria:

Subjects are required to meet NONE of the following criteria for enrollment into the Phase I (Part 1) of the study:

1. Pregnant or lactating females or women who are planning for pregnancy in the next 6 months
2. Women at postpartum for 3 months or less prior to screening
3. Serious medical illnesses such as end-stage renal disease, liver failure or heart failure that, in the opinion of the Investigator may interfere with the conduct of the study
4. Subjects with abnormal vital signs, physical and dermatological exams or clinical laboratory evaluations considered clinically significant by the Principal Investigator, which in the opinion of the PI would significantly interfere with the study conduct
5. Subjects with any concurrent skin condition that could interfere with the evaluation of the treatment areas, as determined by the investigator
6. The subject has a planned major surgical intervention for a pre-existing condition within the duration of the study
7. The subject has a history of drug or alcohol abuse that would impair or risk the subject's full participation in the study, in the opinion of the investigator.
8. Participation in a clinical trial within 3 months, or more than two clinical trials within 12 months prior to screening
9. Concurrent or recent use of topical steroids, topical immunosuppressive/immunomodulative drugs, topical vitamin D3 derivative, topical retinoids, anthralin, coal tar (except when used as shampoo) or salicylic acid within 14 days of the baseline visit
10. The subject has severe AD as determined by vIGA-AD™ score higher than 3
11. The subject cannot avoid systemic treatments (including systemic corticosteroids, immunotherapy, biologics or phototherapy) for AD during the study per the Investigator
12. The subject has previously received any systemic treatments, immunotherapy, biologics or phototherapy for AD within 12 months prior to study enrollment
13. Current or expected use of prohibited medications as described in Section 7, unless approved by the study Medical Monitor
14. The subject has concurrent contact dermatitis or history of anaphylactic reaction

Part 2 Inclusion Criteria:

Subjects are required to meet ALL of the following criteria for randomization into the Phase II (Part 2) of the study:

1. Male or female subjects who are 18 years or older.

2. If female and not infertile (defined below), the subject must agree for the duration of the study to use one of the following forms of contraception 1) systemic hormonal treatment 2) an intrauterine device (IUD) which was implanted at least 2 months prior to screening or 3) "double-barrier" contraception (condom, diaphragm and spermicide are each considered a barrier). Females are considered to be infertile if they are either a) surgically sterile or b) have had spontaneous amenorrhea for at least the last 2 years and at least 2 years after the onset of amenorrhea while not receiving hormone replacement therapy.

3. All fertile female subjects as described above need to have a negative urine pregnancy test at the screening and baseline visits.

4. Subject is capable of providing informed consent and is willing to sign the ICF prior to study Screening and agrees to comply with the study protocol requirements.

5. Subject is able to apply topical products on all the treatable areas by self and/or caregiver (if applicable), per the Investigator.

6. Subject is willing and able to comply with all clinic visits and study-related procedures.

7. Subject is able to understand and complete study-related questionnaires.

8. The subject has physician confirmed mild to moderate Atopic Dermatitis (AD) defined by the Eichenfield revised criteria of Hannifin and Rajka, for at least 6 months prior to study enrollment.

9. Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD™) score of 2 or 3 (mild to moderate) at the screening and baseline visits.

10. Eczema Area and Severity Index (EASI) score lower than 23 at the screening and baseline visits

11. Subject has Atopic Dermatitis (AD) involvement of between 5% and 30% of the treatable BSA (excluding the scalp, face, eyes, eyelids, hands, palms, feet, groin, genitals or the axillae) appropriate for topical treatment at the screening and baseline visits.

    Note: Calculation of Treatable BSA percentage (% of the total BSA that is AD-involved, excluding the scalp, face, eyes, eyelids, hands, palms, feet, groin, genitals or the axillae) will be completed by the "Rule of Nines" method:

    o Where values of 9% or 18% of BSA are assigned to specific regions in the adult subject (head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%])

12. Subjects must be applying stable doses of an additive-free, basic bland emollient twice-daily for at least 1 week immediately before the baseline visit (Visit 2, Day 0), and to be continued throughout the study.

Note: The additive-free, basic bland emollients should be applied no earlier than 1 hour before or after the administration of the study treatment.

Part 2 Exclusion Criteria:

Subjects are required to meet NONE of the following criteria for randomization into the Phase II (Part 2) of the study:

1. Pregnant or lactating females or women who are planning for pregnancy in the next 6 months
2. Women at postpartum for 3 months or less prior to screening
3. Serious medical illnesses such as end-stage renal disease, liver failure or heart failure that, in the opinion of the Investigator may interfere with the conduct of the study
4. Subjects with abnormal vital signs, physical and dermatological exams or clinical laboratory evaluations considered clinically significant by the Principal Investigator, which in the opinion of the PI would significantly interfere with the study conduct
5. Subjects with any concurrent skin condition that could interfere with the evaluation of the treatment areas, as determined by the investigator
6. The subject has a planned major surgical intervention for a pre-existing condition within the duration of the study
7. The subject has a history of drug or alcohol abuse that would impair or risk the subject's full participation in the study, in the opinion of the investigator.
8. Participation in a clinical trial within 3 months, or more than two clinical trials within 12 months prior to screening
9. Concurrent or recent use of prescription moisturizers, topical steroids, topical immunosuppressive/immunomodulative drugs, topical vitamin D3 derivative, topical retinoids, anthralin, coal tar (except when used as shampoo) or salicylic acid within 14 days of the baseline visit
10. The subject has severe AD as determined by vIGA-AD™ score higher than 3
11. The subject cannot avoid systemic treatments (including systemic corticosteroids, immunotherapy, biologics or phototherapy) for AD during the study per the Investigator
12. The subject has previously received any systemic treatments, immunotherapy, biologics or phototherapy for AD within 12 months prior to study enrollment
13. Current or expected use of prohibited medications and procedures during study treatment, as described in Section 7, unless approved by the study Medical Monitor
14. Subject has unstable AD or any consistent requirement for high-potency topical corticosteroids to manage AD signs and symptoms
15. Subject has a significant active systemic or localized infection, including known actively infected AD
16. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit
17. The subject has previously received AMTX-100 CF
18. Subject has any other medical or psychological condition (including relevant laboratory abnormalities at screening) that, in the opinion of the investigator, may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study patient as a result of his/her participation in this clinical trial, may make patient's participation unreliable, or may interfere with study assessments
19. The subject has concurrent contact dermatitis; or history of anaphylactic reaction