A Phase 2, Muti-Center Study of Repeat Dosing of Squaric Acid Dibutyl Ester in Subjects With Herpes Labialis
Condition: Herpes Labialis; HSV
MeSH terms: Herpes Simplex; Herpes Labialis
Intervention: Squaric Acid Dibutyl Ester
Intervention description: Repeat topical application of 2% and 0.5% squaric acid dibutyl ester (SADBE) in subjects with frequent herpes labialis (4 or more episodes in the previous 12 months).
Intervention MeSH terms: Squaric acid dibutyl ester
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will receive on a double blind basis one of two treatment regimens:
Group A: 15 subjects, treated with 2% SADBE on day 0 and with 2% SADBE on the visits at week 3, week 6, week 9, and month 8.
Group B: 15 subjects, treated with 2% SADBE on day 0 and with 0.5% SADBE on the visits at week 3, week 6, week 9, and month 8.
And subjects will be recruited on an open label basis to two other treatment regimens:
Group C: 15 subjects, treated with 2% SADBE on day 0, month 3, and month 6.
Group D: 15 subjects, treated with 2% SADBE on day 0 and month 6.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: The double-blinding only applies between groups A and B. Subjects for groups C and D will be recruited on an open label basis.
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Squaric Acid; SADBE; Squaric acid dibutyl ester

Summary:

      Primary Objective: To assess local and generalized adverse events with repeat topical
      application of 2% and 0.5% squaric acid dibutyl ester (SADBE) in subjects with frequent
      herpes labialis (4 or more episodes in the previous 12 months).

      Secondary Objective: To assess efficacy of repeat topical application of 2% and 0.5% SADBE in
      the prevention of herpes labialis episodes.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 18 and ≤ 65

          2. Clinical diagnosis of herpes labialis, which may be made at the screening visit based
             on the patient's self-reported history of symptoms. An active herpes labialis outbreak
             at the time of entry into the clinical trial will neither be required nor will be an
             exclusion criterion.

          3. Self report having four (4) or more episodes of herpes labialis in the past 12 months.

             Subjects will NOT be told that four-or-more episodes in the previous 12 months is the
             entry criterion. Subjects will be asked "How many separate episodes of cold sores have
             you had in the previous 12 months?" They will be included if they give an answer of
             four or more and excluded if they give an answer of three or fewer.

          4. At least half of the subject's episodes of the previous 12 months should be vesicular
             in nature and at least half preceded by prodromal symptoms. Prodromal symptoms may
             include tingling, itching, burning or pain before the development of a herpetic
             lesion.

        Exclusion Criteria:

          1. Pregnant or lactating females.

          2. Current or recurrent non-herpetic infection or any underlying condition that may
             predispose to infection or anyone who has been admitted to the hospital due to
             bacteremia, pneumonia or any other serious infection in the last 12 months.

          3. Therapy with glucocorticoid or immunosuppressants at time of recruitment or within
             past 4 weeks prior to the screening visit, or at any time during the study (including
             inhaled corticosteroids for asthma), except for topical steroids in sites other than
             face.

          4. History of malignancy (except patients with surgically cured basal cell or squamous
             cell skin cancers).

          5. History of organ transplantation.

          6. HIV-positive status determined by history at screening or known history of any other
             immunosuppressive disease.

          7. Severe co-morbidities (CHF [NYHA class II or worse], MI, CVA or TIA) within 3 months
             of screening visit, current unstable angina pectoris or oxygen-dependent severe
             pulmonary disease.

          8. Known hypersensitivity to Dimethyl sulfoxide (DMSO).

          9. Any condition judged by the investigator to cause this clinical trial to be
             detrimental to the patient.

         10. Subject is currently enrolled in another investigational device or drug trial(s), or
             subject has received other investigational agent(s) within 28 days of the screening
             visit.

         11. Previous exposure to SADBE (squaric acid or squaric acid dibutyl ester).

         12. Subject has an abnormal skin condition (e.g., acne, eczema, rosacea, psoriasis,
             albinism, or chronic vesiculo-bullous disorder) that occurs in the area ordinarily
             affected by herpes labialis

         13. Subject has an abnormal skin condition (e.g., eczema, rosacea, psoriasis, albinism, or
             chronic vesiculo-bullous disorder) that occurs in the inner aspect of either upper arm
             (the area where drug will be applied).

         14. Subject has had a vaccine for either HSV-1 or HSV-2.

         15. Subject has had treatment with anti-viral therapy (including ABREVA) within 2 weeks
             before first dose of SADBE or at any time during the study.