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A Double-blind, Intra-individual Comparison, POC Trial of AC-203 in EB Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03468322
Recruitment Status : Completed
First Posted : March 16, 2018
Last Update Posted : April 16, 2019
Information provided by (Responsible Party):
TWi Biotechnology, Inc.

Brief Summary:

Inherited epidermolysis bullosa (EB) is a genetic skin disorder characterized by skin fragility and recurrent blister formation. More and more evidence has suggested that the skin lesions initially caused by genetic mutations may be further aggravated by inflammatory responses. Several reports showed successful alleviation of EB symptoms upon treatment with immunomodulatory therapies. Modulation of proinflammatory cytokine IL-1β has shown promising results in alleviating epidermolysis bullosa simplex (EBS), a major subtype of inherited EB, by downregulating IL-1β-mediated JNK/MAPK signaling pathway. This data further supports the potential of using cytokine modulators to treat EB.

AC-203, a topical formulation, can inhibit the production and activity of IL-1β, down-regulate IL-1β receptors, and increase IL1β-receptor antagonist (IL1-Ra) expression. In addition, AC-203 has been reported to inhibit anti-BP180 autoantibody-induced IL-6/IL-8 upregulation in cultured keratinocytes and LPS-induced IL-6 upregulation in cultured macrophages. Furthermore, AC-203 was also found to inhibit the formation of NLRP3 inflammasome, which plays essential roles in induction of caspase-1-dependent pyroptosis and release of inflammatory cytokines IL-1β and IL-18. These studies demonstrated the cytokine modulatory properties of AC-203 and pointed out the possible application of AC-203 in a variety of inflammatory diseases.

This study is designed to test the efficacy, safety, tolerability, and pharmacokinetics of AC-203 ointment (vs. placebo) in patients with inherited EB.

Condition or disease Intervention/treatment Phase
Inherited Epidermolysis Bullosa Drug: AC-203 Drug: Vehicle Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Intra-individual comparison
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Intra-individual Comparison, Proof-of-concept Trial of Topical AC-203 in Patients With Inherited Epidermolysis Bullosa
Actual Study Start Date : October 20, 2018
Actual Primary Completion Date : April 9, 2019
Actual Study Completion Date : April 9, 2019

Arm Intervention/treatment
Experimental: AC-203 1% ointment
AC-203 1% ointment, QD
Drug: AC-203
The investigational product is formulated as 1% topical ointment

Placebo Comparator: Vehicle ointment
Vehicle ointment, QD
Drug: Vehicle
Vehicle-only control study medication is the same formulation as investigational product without active ingredient

Primary Outcome Measures :
  1. Percentage change in lesion surface area from baseline by treatment [ Time Frame: 2, 4, 5, 6, 8, 12 Weeks ]

Secondary Outcome Measures :
  1. Percentage change in blister number from baseline by treatment [ Time Frame: 2, 4, 5, 6, 8, 12 Weeks ]
  2. Proportion of subjects with at least 40% reduction in blister number from baseline by treatment [ Time Frame: 2, 4, 5, 6, 8, 12 Weeks ]
  3. Pruritus assessment scale changes from baseline by treatment [ Time Frame: 2, 4, 5, 6, 8, 12 Week ]
    100-mm line (anchored at 0 mm for no pruritus, 100 mm for worst possible pruritus)

  4. Pain assessment scale changes from baseline by treatment [ Time Frame: 2, 4, 5, 6, 8, 12 Weeks ]
    100-mm line (anchored at 0 mm for no pruritus, 100 mm for worst possible pruritus)

  5. IL-1beta concentrations and changes from baseline [ Time Frame: 8 Weeks ]
  6. hsCRP concentrations and changes from baseline [ Time Frame: 8 Weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Subject is at least 2 years of age.
  2. Subject has a clinical diagnosis of EB.
  3. Subject has a laboratory confirmed diagnosis of inherited EB based on electron microscopy and/or immunofluorescence antigenic mapping.
  4. Subject has two comparable areas with 1% - 5% BSA each. These two areas could be on any body surface except the face, scalp, groin, palms and soles. Percentage BSA of the designated areas within subject should be the same. Comparable areas are defined as having similar lesion (i.e., blisters, erosions, erythema and crusts) history and current lesion status by investigator's judgement on each area at Screening Visit (Visit 1) and Day 1 (Visit 2).
  5. Is male, or is female and meets all the following criteria:

    1. Not breastfeeding
    2. If of childbearing potential (defined as non-post-hysterectomy or non-post-menopausal [≥50 years of age and amenorrheic for at least 1 year]), must have a negative pregnancy test result at Visit 1, and must practice and be willing to continue to practice appropriate birth control during the entire duration of the study.
  6. Is able to read, understand, and sign the Informed Consent Form (ICF), answer the study questionnaires, communicate with the investigator, and understand and comply with protocol requirements, OR Informed consent received from subject's parents/caregiver or legal guardian (when subject < 20 years).

Exclusion Criteria:

  1. Subject has a current malignancy, or a history of treatment for a malignancy within two years.
  2. Systemic infections.
  3. Subjects who are pregnant, lactating, or planning a pregnancy during the study.
  4. History of allergy or hypersensitivity to any component of study medication.
  5. Any other significant diseases, conditions, or laboratory values which, in the opinion of the investigator, might make participation not in the subject's best interest or confound the interpretation of study results.
  6. Any prior use of approved or investigational biologic anti-inflammatory therapy within 6 months prior to screening, including but not limited to: anakinra, rilonacept, canakinumab, etanercept, adalimumab, infliximab, rituximab, certolizumab, golimumab, tocilizumab, bertilimumab, or abatacept.
  7. Use of non-steroid immunosuppressants including but not limited to azathioprine, mycophenolate, cyclophosphamide, chlorambucil, methotrexate, tacrolimus, or cyclosporine in the 2 weeks prior to screening.
  8. Has been treated with gentamicin within 90 days prior to screening (Note: products containing gentamicin used on eyes are allowed).
  9. Has been treated with minocycline, oxytetracycline, tetracycline or doxycycline within 7 days prior to screening.
  10. Subjects has used any topical allantoin ≥ 3% within 30 days prior to screening.
  11. Has been treated systemic steroid within 30 days prior to screening.
  12. Prior treatment with any investigational therapy within 30 days prior to screening.
  13. Is an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the clinical study site, or is directly affiliated with the study at the clinical study site.
  14. Is employed by sponsor (i.e., is an employee, temporary contract worker, or designee responsible for the conduct of the study).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03468322

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Mackay Memorial Hospital
Hsinchu, Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan
Sponsors and Collaborators
TWi Biotechnology, Inc.
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Responsible Party: TWi Biotechnology, Inc. Identifier: NCT03468322    
Other Study ID Numbers: AC-203-EBS-005
First Posted: March 16, 2018    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Epidermolysis Bullosa
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous