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

Inherited Epidermolysis Bullosa Clinical Trial

Official title:

A Double-blind, Intra-individual Comparison, Proof-of-concept Trial of Topical AC-203 in Patients With Inherited Epidermolysis Bullosa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03468322
• Other study ID #: AC-203-EBS-005
• Status: Completed
• Phase: Phase 2
• Start date: October 20, 2018
• Est. completion date: April 9, 2019

Study information

• Verified date: April 2019
• Source: TWi Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: April 9, 2019
• Est. primary completion date: April 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Epidermolysis Bullosa
• Inherited Epidermolysis Bullosa

Intervention

Drug:
• AC-203
The investigational product is formulated as 1% topical ointment
• Vehicle
Vehicle-only control study medication is the same formulation as investigational product without active ingredient

Locations

Country	Name	City	State
Taiwan	Mackay Memorial Hospital	Hsinchu
Taiwan	National Cheng Kung University Hospital	Tainan

Sponsors (1)

Lead Sponsor	Collaborator
TWi Biotechnology, Inc.

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in lesion surface area from baseline by treatment		2, 4, 5, 6, 8, 12 Weeks
Secondary	Percentage change in blister number from baseline by treatment		2, 4, 5, 6, 8, 12 Weeks
Secondary	Proportion of subjects with at least 40% reduction in blister number from baseline by treatment		2, 4, 5, 6, 8, 12 Weeks
Secondary	Pruritus assessment scale changes from baseline by treatment	100-mm line (anchored at 0 mm for no pruritus, 100 mm for worst possible pruritus)	2, 4, 5, 6, 8, 12 Week
Secondary	Pain assessment scale changes from baseline by treatment	100-mm line (anchored at 0 mm for no pruritus, 100 mm for worst possible pruritus)	2, 4, 5, 6, 8, 12 Weeks
Secondary	IL-1beta concentrations and changes from baseline		8 Weeks
Secondary	hsCRP concentrations and changes from baseline		8 Weeks