Immune Response and General Immune Health in Subjects Infected With Herpes Simplex Virus Type 1 (HSV-1)

NCT03661541 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 2017-SQ-Prism
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Subjects were recruited who were positive for antibody against herpes simplex virus type 1 (HSV-1) and self-reported having in the previous 12 months

• 6 or more herpes labialis outbreaks (group A),
• 1 or 2 outbreaks (group B), or
• zero outbreaks (group C). Twelve subjects in each group were recruited. Blood was collected from these persons and peripheral blood mononuclear cells (PBMCs) isolated and tested for proliferation in vitro when stimulated with HSV-1-infected cell extracts, free HSV-1 virus, or Candida albicans extract. Candida albicans is a ubiquitous infectious fungus and its extract is used as a test of general immune response. RNA was also isolated from the PBMCs after incubation in the three stimuli and expression of 41 immune-related genes quantified by quantitative real-time PCR. Also serum anti-HSV-1 IgG levels were quantified. After the blood collection on day 1, the persons in group A (frequent cold sore sufferers) were treated with a single topical application of 2% squaric acid dibutyl ester (SADBE) in DMSO, applied to the inner aspect of the upper arm. These subjects returned on days 15 and 57 for blood collection, and their PBMCs were tested again on those dates for proliferation in vitro against the same stimuli and for gene expression and for serum anti-HSV-1 IgG levels.

Conditions

HSV; Herpes Labialis

Keywords

Squaric Acid; Squaric acid dibutyl ester; cold sores

Outcome Measures

Primary Outcomes (3)

• Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline

  RNA gene expression of interleukin-5 (IL5) and interferon gamma (IFNG) genes in PBMCs exposed in vitro to 4 conditions: no stimulus, HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract. Measure is qRT-PCR crossing threshold (Ct), where a lower number is higher gene expression. A lower Ct of 1 is approximately a 2-fold higher expression level of the gene.

  Baseline and 8 weeks after baseline (Day 1) +/- 7 days for subjects with less than 6 herpres labialis outbreaks in 12 months, relative to baseline for subjects with 6 or greater herpes labialis outbreaks

• Immune Monitoring - PBMC Proliferation

  PBMC proliferation in response to 3 stimuli: HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract.

  Baseline

• Immune Monitoring - PBMC Proliferation

  PBMC proliferation in response to 3 stimuli: HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract.

  Day 1 and 8 weeks from Day 1 (Initial visit) +/- 7 days for subjects with 6 or more herpes labalis outbreaks

Study Arms (3)

Group A, 6 or more outbreaks per 12 months

EXPERIMENTAL

Subjects will be recruited in three groups, all of whom are infected with HSV-1, as shown by having IgG against HSV-1: Group A: 12 subjects with 6 or more herpes labialis outbreaks in the past 12 months. Subjects in group A will receive 2% Squaric Acid Dibutyl Ester (SADBE) dose on the arm after their initial blood samples are obtained. Group A subjects will have blood collected and tests repeated 2 and 8 weeks later. Subjects in Groups B and C will be matched to the subjects in Group A so that demographic characteristics (i.e., gender distribution, age and weight) are within broadly similar ranges.

Drug: Squaric Acid Dibutyl Ester

Group B, 1 or 2 outbreaks per 12 months

NO INTERVENTION

Subjects will be recruited in three groups, all of whom are infected with HSV-1, as shown by having IgG against HSV-1: Group B: 12 subjects with 1 to 2 outbreaks in the past 12 months. Subjects in Groups B and C will be matched to the subjects in Group A so that demographic characteristics (i.e., gender distribution, age and weight) are within broadly similar ranges. Invite these back for a further blood draw on Day 0.

Group C, zero outbreaks per 12 months

NO INTERVENTION

Subjects will be recruited in three groups, all of whom are infected with HSV-1, as shown by having IgG against HSV-1: Group C: 12 subjects with zero outbreaks in the past 12 months. Subjects in Groups B and C will be matched to the subjects in Group A so that demographic characteristics (i.e., gender distribution, age and weight) are within broadly similar ranges. Invite these back for a further blood draw on Day 0.

Interventions

Squaric Acid Dibutyl Ester DRUG

2% squaric acid dibutyl ester (SADBE) (Supplied by Squarex) is topically applied to the inner aspect of the upper arm of the subject and covered with Tegaderm. Subject is advised to wash it off after 3 hours.

Also known as: SADBE

Group A, 6 or more outbreaks per 12 months

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and \<65
• Positive test for IgG against herpes simplex virus type 1 (HSV-1).

You may not qualify if:

• Group A only: Self report having six or more episodes of herpes labialis in the past 12 months. Subjects will NOT be told that six-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 six or more and excluded from Group A if they give an answer of five or fewer.
• Group A only: 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.
• Group B only: Self report having exactly 1 or 2 episodes of herpes labialis in the past 12 months. Subjects will NOT be told that one or two 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 one or two and excluded from Group B if they give a different answer.
• Group C only: Self report having zero episodes of herpes labialis in the past 12 months. Subjects will NOT be told that zero 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 zero and excluded from Group C if they give an answer of one or more.
• Pregnant or lactating females.
• 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.
• Therapy with glucocorticoid or immunosuppressants at time of recruitment or within past 4 weeks prior to the screening visit (including inhaled corticosteroids for asthma), except for topical steroids in sites other than face.
• History of malignancy (except patients with surgically cured basal cell or squamous cell skin cancers).
• History of organ transplantation.
• HIV-positive status determined by history at screening or known history of any other immunosuppressive disease.
• Severe co-morbidities (diabetes mellitus requiring insulin, CHF (NYHA class II or worse) MI, CVA or TIA within 3 months of screening visit, unstable angina pectoris, oxygen-dependent severe pulmonary disease
• Known hypersensitivity to Dimethyl sulfoxide (DMSO).
• Any condition judged by the investigator to cause this clinical trial to be detrimental to the patient.
• Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.
• Previous exposure to SADBE (squaric acid or squaric acid dibutyl ester).

Sponsors & Collaborators

• Squarex, LLC: lead

Study Sites (1)

Prism Clinical Research, LLC

Saint Paul, Minnesota, 55114, United States

Location

Related Publications (1)

• McTavish H, Zerebiec KW, Zeller JC, Shekels LL, Matson MA, Kren BT. Immune characteristics correlating with HSV-1 immune control and effect of squaric acid dibutyl ester on immune characteristics of subjects with frequent herpes labialis episodes. Immun Inflamm Dis. 2019 Mar;7(1):22-40. doi: 10.1002/iid3.241. Epub 2019 Feb 12.

  PMID: 30756512 RESULT

MeSH Terms

Conditions

Herpes Labialis

Interventions

squaric acid dibutyl ester

Condition Hierarchy (Ancestors)

Herpes Simplex; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Lip Diseases; Mouth Diseases; Stomatognathic Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Hugh McTavish
• Organization: Squarex LLC

hmctavish@squarex-pharma.com

6512078270

Study Officials

• Mark Matson, MD

  Prism Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be recruited in three groups, all of whom are infected with HSV-1, as shown by having IgG against HSV-1: x Group A: 12 subjects with 6 or more herpes labialis outbreaks in the past 12 months x Group B: 12 subjects with 1 to 2 outbreaks in the past 12 months x Group C: 12 subjects with zero outbreaks in the past 12 months Subjects in group A will receive 2% SADBE dose on the arm after their initial blood samples are obtained. Group A subjects will have blood collected and tests repeated 2 and 8 weeks later. Subjects in Groups B and C will be matched to the subjects in Group A so that demographic characteristics (i.e., gender distribution, age and weight) are within broadly similar ranges.

Study Record Dates

• First Submitted: May 1, 2018
• First Posted: September 7, 2018
• Study Start: March 2, 2017
• Primary Completion: June 17, 2017
• Study Completion: October 25, 2017
• Last Updated: November 3, 2021
• Results First Posted: November 3, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)