Herpes LabialisPhase 2NCT03521479
A Phase 2, Muti-Center Study of Repeat Dosing of Squaric Acid Dibutyl Ester in Subjects With Herpes Labialis
A Phase 2 study testing Squaric Acid Dibutyl Ester in people with Herpes Labialis and HSV, run by Squarex, LLC at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Herpes Labialis, HSV
- What is being tested?
- Squaric Acid Dibutyl Ester
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- 12 Mar 2018to 5 Oct 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 and ≤ 65
- 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.
- 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.
- 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.
Who cannot join
- 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, or at any time during the study (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.
Show all 15Show fewer
- 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.
- 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 the screening visit.
- Previous exposure to SADBE (squaric acid or squaric acid dibutyl ester).
- 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
- 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).
- Subject has had a vaccine for either HSV-1 or HSV-2.
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
International Research Partners, LLC
Doral, Florida, 33166
Prism Clinical Research, LLC
Saint Paul, Minnesota, 55114
About this study
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.
Read the detailed description
Primary oral infection with the herpes simplex virus (HSV) typically occurs at a young age, is asymptomatic, and is not associated with significant morbidity. After primary oral infection, HSV may persist in a latent state in the trigeminal ganglion and later reactivate as the more common herpes labialis, or "cold sores." Common triggers for reactivation are well known and include ultraviolet light, trauma, fatigue, stress, fever, inflammation, and menstruation. These lesions affect up to 45 percent of the U.S. population. They classically manifest as a well-localized cluster of small vesicles along the vermilion border of the lip or adjacent skin. The vesicles subsequently rupture, ulcerate, and crust within 24 to 48 hours. Spontaneous healing occurs over seven to 10 days.
In immunocompetent patients, herpes labialis usually is mild and self-limited. However, pain, swelling, and cosmetic concerns may prompt physician consultation. Orally administered antiviral agents, such as acyclovir (Zovirax) or valacyclovir (Valtrex), have a modest clinical benefit if initiated during the prodrome. Topical treatment with 1% penciclovir cream (Denavir) may reduce healing time and pain slightly, even if initiated after the prodrome. However, reduction in healing time with systemic or topical agents is modest.
Squaric acid dibutyl ester (SADBE) is a topical immunotherapeutic agent used in the treatment of verruca vulgaris and alopecia areata. During a recent FDA Compounding Advisory Committee Meeting, it was recommended that squaric acid dibutylester be included on the list of bulk drug substances allowed for use in compounding under section 503A of the Federal Food, Drug, and Cosmetic Act. And SADBE has now been so listed under section 503A.
A study completed by Lee et al of 29 patients with recalcitrant warts demonstrated complete clearance in 69% of patients with application every 2-4 weeks. Silverberg et al showed a complete clearance in 58% of patients (n=61) when SADBE was applied 3 times weekly. A placebo-controlled clinical study completed at Massachusetts General Hospital showed that squaric acid prevented recurrence of herpetic lesions. The effect of SADBE of delaying new herpes labialis outbreaks was highly significant (p<0.01) as compared to placebo.
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.
- Conditions
- Herpes Labialis, HSV
- Being tested
- Squaric Acid Dibutyl Ester
- Keywords
- Squaric Acid, SADBE, Squaric acid dibutyl ester
- Medical subject headings
- Herpes Labialis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Squaric Acid Dibutyl EsterDrug
Also called Repeat Dosing
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).
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Treated with 2% Squaric Acid Dibutyl Ester (SADBE) on day 0 and with 2% SADBE on the visits at week 3, week 6, week 9, and month 8. Receives: Drug: Squaric Acid Dibutyl Ester |
| Group B | Experimental | Treated with 2% Squaric Acid Dibutyl Ester (SADBE) on day 0 and with 0.5% SADBE on the visits at week 3, week 6, week 9, and month 8. Receives: Drug: Squaric Acid Dibutyl Ester |
| Group C | Active comparator | Treated with 2% Squaric Acid Dibutyl Ester (SADBE) on day 0, month 3, and month 6. Receives: Drug: Squaric Acid Dibutyl Ester |
| Group D | Active comparator | Treated with 2% Squaric Acid Dibutyl Ester (SADBE) on day 0 and month 6. Receives: Drug: Squaric Acid Dibutyl Ester |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local and Generalized Adverse Events
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).
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2018
- Study start12 Mar 2018
- Primary completion5 Oct 2018
- Study completion5 Oct 2019
Why it stopped: Study drug out of specification
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Herpes LabialisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Squarex, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03521479
- Sponsor's protocol ID
- P2c
- Status last verified
- Aug 2021
- First submitted
- 29 Apr 2018
- Last updated
- 6 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Muti-Center Study of Repeat Dosing of Squaric Acid Dibutyl Ester in Subjects With Herpes Labialis
- ClinicalTrials.gov ID
- NCT03521479
- Acronym / sponsor ID
- P2c
- Conditions
- Herpes Labialis, HSV
- Keywords
- Squaric Acid, SADBE, Squaric acid dibutyl ester
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study drug out of specification
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Squarex, LLCIndustry (pharma, biotech, devices)
- Study start
- 12 Mar 2018 (actual)
- Primary completion
- 5 Oct 2018 (actual)
- Study completion
- 5 Oct 2019 (actual)
- First posted
- 11 May 2018 (actual)
- Results
- Posted 15 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Primary oral infection with the herpes simplex virus (HSV) typically occurs at a young age, is asymptomatic, and is not associated with significant morbidity. After primary oral infection, HSV may persist in a latent state in the trigeminal ganglion and later reactivate as the more common herpes labialis, or "cold sores." Common triggers for reactivation are well known and include ultraviolet light, trauma, fatigue, stress, fever, inflammation, and menstruation. These lesions affect up to 45 percent of the U.S. population. They classically manifest as a well-localized cluster of small vesicles along the vermilion border of the lip or adjacent skin. The vesicles subsequently rupture, ulcerate, and crust within 24 to 48 hours. Spontaneous healing occurs over seven to 10 days.
In immunocompetent patients, herpes labialis usually is mild and self-limited. However, pain, swelling, and cosmetic concerns may prompt physician consultation. Orally administered antiviral agents, such as acyclovir (Zovirax) or valacyclovir (Valtrex), have a modest clinical benefit if initiated during the prodrome. Topical treatment with 1% penciclovir cream (Denavir) may reduce healing time and pain slightly, even if initiated after the prodrome. However, reduction in healing time with systemic or topical agents is modest.
Squaric acid dibutyl ester (SADBE) is a topical immunotherapeutic agent used in the treatment of verruca vulgaris and alopecia areata. During a recent FDA Compounding Advisory Committee Meeting, it was recommended that squaric acid dibutylester be included on the list of bulk drug substances allowed for use in compounding under section 503A of the Federal Food, Drug, and Cosmetic Act. And SADBE has now been so listed under section 503A.
A study completed by Lee et al of 29 patients with recalcitrant warts demonstrated complete clearance in 69% of patients with application every 2-4 weeks. Silverberg et al showed a complete clearance in 58% of patients (n=61) when SADBE was applied 3 times weekly. A placebo-controlled clinical study completed at Massachusetts General Hospital showed that squaric acid prevented recurrence of herpetic lesions. The effect of SADBE of delaying new herpes labialis outbreaks was highly significant (p<0.01) as compared to placebo.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Squaric Acid Dibutyl EsterTreated with 2% Squaric Acid Dibutyl Ester (SADBE) on day 0 and with 2% SADBE on the visits at week 3, week 6, week 9, and month 8. |
| Group B | Experimental | Drug: Squaric Acid Dibutyl EsterTreated with 2% Squaric Acid Dibutyl Ester (SADBE) on day 0 and with 0.5% SADBE on the visits at week 3, week 6, week 9, and month 8. |
| Group C | Active comparator | Drug: Squaric Acid Dibutyl EsterTreated with 2% Squaric Acid Dibutyl Ester (SADBE) on day 0, month 3, and month 6. |
| Group D | Active comparator | Drug: Squaric Acid Dibutyl EsterTreated with 2% Squaric Acid Dibutyl Ester (SADBE) on day 0 and month 6. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 and ≤ 65
- 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.
- 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.
- 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.
Key exclusion criteria (15 listed)
- 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, or at any time during the study (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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Squaric Acid Dibutyl EsterAlso: Repeat DosingRepeat 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). | Drug | Group A, Group B, Group C, Group D |
Primary outcome
Local and Generalized Adverse Events
Time frame: 9 months
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Herpes Labialis
RecruitingObservational study
Viral Infections in Healthy and Immunocompromised Hosts
Anogenital Herpes, COVID-19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Squaric Acid Dibutyl Ester in people with Herpes Labialis and HSV, run by Squarex, LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local and Generalized Adverse Events (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2021.