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

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ClinicalTrials.gov Identifier: NCT04313400
Recruitment Status : Recruiting
First Posted : March 18, 2020
Last Update Posted : March 18, 2020
Sponsor:
Collaborator:
Amarex Clinical Research
Information provided by (Responsible Party):
Amytrx Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE March 16, 2020
First Posted Date  ICMJE March 18, 2020
Last Update Posted Date March 18, 2020
Actual Study Start Date  ICMJE March 10, 2020
Estimated Primary Completion Date January 3, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2020)
  • Part 1 (Phase I) Primary: Maximum Tolerable Dose [ Time Frame: Over the 7 day treatment period ]
    Maximum Tolerable Dose (MTD) by maximum percentage of Body Surface Area (BSA) treated, by evaluation of dose-limiting toxicity (DLT) of AMTX-100 CF (1.1% w/w concentration) based on the safety profile
  • Part 2 (Phase II) Primary: Proportion of responder subjects at Day 28 [ Time Frame: At Day 28 ]
    Proportion of responder subjects at Day 28, defined as subjects with both Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) score of 0 (clear) or 1 (almost clear) (on a 5-point scale) and a reduction of ≥ 2 points from baseline
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Topically Applied AMTX-100 CF for Adult Patients With Mild to Moderate Atopic Dermatitis
Official Title  ICMJE 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
Brief Summary

This study determines the Maximum Tolerable Dose (MTD) by maximum BSA percentage treated and evaluates efficacy of various concentrations of 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 One Hundred Twenty (120) 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 different concentrations of AMTX-100 CF (low concentration (0.11% w/w), medium concentration (0.33% w/w) and high concentration (1.1% w/w)) or Vehicle (Placebo) in the study.

Detailed Description

AMTX-100 CF 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 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 metabolic products.

AMTX-100 CF is intended for improvement of 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 various concentrations of AMTX-100 CF versus placebo (vehicle).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

Part 1 (Phase I):

Part 1 of the study is an open-label, dose escalation study to determine the MTD of AMTX-100 CF (1.1% w/w) for the highest treated percentage of the BSA affected with AD. Five (5) cohorts will be sequentially enrolled in the Part 1 of the study. Each cohort will include five (5) patients with eligible, treatable percentages of BSA affected with AD.

Part 2 (Phase II):

Part 2 of the study is a multi-center, double-blind, randomized, vehicle-controlled, dose ranging study of the safety and efficacy of topically applied AMTX-100 CF in adult patients with Mild to Moderate AD. One hundred twenty (120) patients will be enrolled in 3 groups of AMTX-100 CF along with a placebo (vehicle) group. The patients will be randomized in a 1:1:1:1 ratio with thirty (30) subjects in each group ((Group A: low dose concentration 0.11%, Group B: medium dose concentration 0.33% and Group C: high dose concentration 1.1%) of AMTX-100 CF) and placebo (vehicle 0% w/w)).

Masking: None (Open Label)
Masking Description:
Part 1 (Phase I) of the study is open-labeled. Part 2 (Phase II) of the study is double-blinded (Masking: Participant, Care Provider, Investigator, and Outcomes Assessor).
Primary Purpose: Treatment
Condition  ICMJE Atopic Dermatitis
Intervention  ICMJE
  • Drug: 1.1% w/w AMTX-100 CF
    AMTX-100 CF, topical cream with 1.1% w/w active pharmaceutical ingredient
  • Drug: 0.33% w/w AMTX-100 CF
    AMTX-100 CF, topical cream with 0.33% w/w active pharmaceutical ingredient
  • Drug: 0.11% w/w AMTX-100 CF
    AMTX-100 CF, topical cream with 0.11% w/w active pharmaceutical ingredient
  • Drug: Placebo
    Topical cream manufactured to mimic AMTX-100 CF
    Other Name: placebo (vehicle 0% w/w)
Study Arms  ICMJE
  • Experimental: Part 1 Dose Escalation: 3% to 70% of the BSA
    Open-label AMTX-100 CF 1.1% w/w, topically applied twice a day for 7 consecutive days to all treatable AD affected areas from 3% to 70% of the Body Surface Area (BSA) (3% BSA ≤ AD Affected Area ≤ 70% BSA)
    Intervention: Drug: 1.1% w/w AMTX-100 CF
  • Experimental: Part 2 Group A: Low dose concentration (0.11% w/w)
    AMTX-100 CF Low dose concentration (0.11% w/w), topically applied twice a day for 28 consecutive days to all treatable AD affected areas
    Intervention: Drug: 0.11% w/w AMTX-100 CF
  • Experimental: Part 2 Group B: Medium dose concentration (0.33% w/w)
    AMTX-100 CF Medium dose concentration (0.33% w/w), topically applied twice a day for 28 consecutive days to all treatable AD affected areas
    Intervention: Drug: 0.33% w/w AMTX-100 CF
  • Experimental: Part 2 Group C: High dose concentration (1.1% w/w)
    AMTX-100 CF High dose concentration (1.1% w/w), topically applied twice a day for 28 consecutive days to all treatable AD affected areas
    Intervention: Drug: 1.1% w/w AMTX-100 CF
  • Placebo Comparator: Part 2 Group D: Placebo
    Placebo (Vehicle) (0% w/w), topically applied twice a day for 28 consecutive days to all treatable AD affected areas
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 16, 2020)
145
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 3, 2021
Estimated Primary Completion Date January 3, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 one of the 2 methods below:

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

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 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 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 70% of the treatable BSA (excluding the scalp, face, eyes, eyelids, neck, 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, neck, hands, palms, feet, groin, genitals or the axillae) will be completed by one of the 2 methods below:

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

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yashar Salek, MD, MSc +1 (301)-956-2527 yashars@amarexcro.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04313400
Other Study ID Numbers  ICMJE AMTX100-AD-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Amytrx Therapeutics, Inc.
Study Sponsor  ICMJE Amytrx Therapeutics, Inc.
Collaborators  ICMJE Amarex Clinical Research
Investigators  ICMJE
Study Director: Yashar Salek, MD, MSc Amarex Clinical Research, LLC (Amarex)
PRS Account Amytrx Therapeutics, Inc.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP