Safety and Efficacy of Squaric Acid Dibutyl Ester for the Treatment of Herpes Labialis (Squarex)

• ClinicalTrials.gov Identifier: NCT01971385
• Recruitment Status: Completed
• First Posted: October 29, 2013
• Results First Posted: October 2, 2017
• Last Update Posted: October 2, 2017
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Alexandra Kimball, Massachusetts General Hospital

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Herpes Labialis
• Interventions: Drug: Squaric Acid solution; Drug: Placebo solution
• Enrollment: 54

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	0.2% Squaric Acid	0.5% Squaric Acid	Placebo Solution
Arm/Group Description	0.2% Squaric Acid solution disolved in dimethyl sulfoxide will be applied Squaric Acid solution	0.5% Squaric Acid solution disolved in dimethyl sulfoxide will be applied Squaric Acid solution	Patients in placebo group will be given dimethyl sulfoxide. Placebo solution
Period Title: Overall Study
Started	17	18	19
Completed	14	13	15
Not Completed	3	5	4

Baseline Characteristics

Arm/Group Title		0.2% Squaric Acid	0.5% Squaric Acid	Placebo Solution	Total
Arm/Group Description		0.2% Squaric Acid solution disolved in dimethyl sulfoxide will be applied Squaric Acid solution	0.5% Squaric Acid solution disolved in dimethyl sulfoxide will be applied Squaric Acid solution	Patients in placebo group will be given dimethyl sulfoxide. Placebo solution	Total of all reporting groups
Overall Number of Baseline Participants		17	18	19	54
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	17 participants	18 participants	19 participants	54 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	15 88.2%	18 100.0%	19 100.0%	52 96.3%
	>=65 years	2 11.8%	0 0.0%	0 0.0%	2 3.7%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	17 participants	18 participants	19 participants	54 participants
		44.86 (13.68)	47.21 (9.37)	44.13 (10.88)	44.93 (11.88)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	17 participants	18 participants	19 participants	54 participants
	Female	14 82.4%	13 72.2%	13 68.4%	40 74.1%
	Male	3 17.6%	5 27.8%	6 31.6%	14 25.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	17 participants	18 participants	19 participants	54 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	3 17.6%	0 0.0%	0 0.0%	3 5.6%
	White	13 76.5%	17 94.4%	18 94.7%	48 88.9%
	More than one race	1 5.9%	0 0.0%	0 0.0%	1 1.9%
	Unknown or Not Reported	0 0.0%	1 5.6%	1 5.3%	2 3.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	17 participants	18 participants	19 participants	54 participants
		17	18	19	54
Number of Outbreaks a year; Mean (Standard Deviation); Unit of measure: Frequency per year
	Number Analyzed	17 participants	18 participants	19 participants	54 participants
		7.06 (1.71)	7.81 (1.81)	8.14 (2.42)	7.68 (2.02)

Outcome Measures

1. Primary Outcome

Title	Subjects With at Least One Form of Contact With Study Staff With no Herpes Labialis Outbreaks Within 119 Days of Sensitization
Description	Percent of subjects with no reported herpes labialis outbreak within 119 days of sensitization over total number of subjects after one form of contact with study staff
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

Because most patients who received 2% SADBE for sensitization did not experience another herpes outbreak and thus did not receive a subsequent treatment dose, we grouped both squaric acid treatment arms together for analysis since both groups had received the same sensitization dose of 2%.

Arm/Group Title	2% Squaric Acid Sensitization	Placebo Solution
Arm/Group Description:	2% Squaric Acid solution will be applied for sensitization to the inner arm. Squaric Acid solution	Patients in placebo group will be given dimethyl sulfoxide. Placebo solution
Overall Number of Participants Analyzed	27	15
Measure Type: Number; Unit of Measure: percentage of particpants
	62.96	20

2. Secondary Outcome

Title	Number of Adverse Events Reported
Description	To assess the safety and tolerability of squaric acid solution the number of adverse events in each treatment arm will be collected and compared.
Time Frame	8 months

Outcome Measure Data Not Reported

Adverse Events

Time Frame	8 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	0.2% Squaric Acid		0.5% Squaric Acid		Placebo Solution
Arm/Group Description	0.2% Squaric Acid solution disolved in dimethyl sulfoxide will be applied Squaric Acid solution		0.5% Squaric Acid solution disolved in dimethyl sulfoxide will be applied Squaric Acid solution		Patients in placebo group will be given dimethyl sulfoxide. Placebo solution
All-Cause Mortality
	0.2% Squaric Acid		0.5% Squaric Acid		Placebo Solution
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	0.2% Squaric Acid		0.5% Squaric Acid		Placebo Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0.00%)		0/18 (0.00%)		0/19 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	0.2% Squaric Acid		0.5% Squaric Acid		Placebo Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/17 (52.94%)		6/18 (33.33%)		3/19 (15.79%)
Skin and subcutaneous tissue disorders
Non Serious Itching, Redness, or Swelling † [1]	8/17 (47.06%)	8	5/18 (27.78%)	5	2/19 (10.53%)	2
Other Non Serious AE † [2]	1/17 (5.88%)	1	1/18 (5.56%)	1	1/19 (5.26%)	1
† Indicates events were collected by systematic assessment; [1] Subjects who reported itching, redness, or swelling and were recorded as a non-serious AE; [2] Other AEs that were reported by subjects but were non-serious

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Maria Alora-Palli
• Organization: Massachusetts General Hospital
• Phone: 6177265066
• EMail: mpalli@mgh.harvard.edu

• Responsible Party: Alexandra Kimball, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01971385
• Other Study ID Numbers: 2013P001028
• First Submitted: October 17, 2013
• First Posted: October 29, 2013
• Results First Submitted: March 23, 2017
• Results First Posted: October 2, 2017
• Last Update Posted: October 2, 2017