A Study to Compare Sitavig (Acyclovir) Buccal Tablet With a Placebo in the Treatment of Herpes Labialis in Participants Whose Immune System Works Normally

A Randomized, Multi-Center, Double Blinded, Self-Initiated, Single Treatment Study Comparing Sitavig® (Acyclovir) 50 mg Muco-adhesive Buccal Tablet to Placebo in the Treatment of Herpes Labialis in Immunocompetent Adults

Researchers are looking for a better way to treat people who have recurrent herpes labialis, also known as cold sores. This is a type of viral infection that causes redness and blisters on the mouth and lip and that recurs.

Herpes labialis is caused by a virus called the herpes simplex virus (HSV). The infection is spread when a person comes into direct contact with someone else who has the infection. Once a person becomes infected with HSV, the virus multiplies and spreads, which can cause redness and blistering on the mouth and lip. The blisters crust over and heal. Once healed, the virus is said to go into an "inactive" phase. This means the virus does not cause any symptoms, but still remains in the body. HSV can then become "active" again. This means causing cold sore lesions to reappear. HSV can become active in different ways. Some of these include when a person has a fever, comes into contact with strong sunlight or has a condition that lowers one's immune system It can also happen during a woman's menstrual cycle, also called a period.

In this study, the researchers want to gather additional data on acyclovir 50 mg tablet, an available treatment for herpes labialis. It is a buccal tablet that sticks to the gum inside the mouth and directly treats the infected area to help stop the HSV from multiplying and spreading.

In this study, the researchers want to compare the efficacy of acyclovir 50 mg buccal tablets versus placebo in the treatment of herpes labialis. A placebo is a treatment that looks like the study medicine but does not have any medicine in it. Study participants will include those who have had at least 4 episodes of herpes labialis within the past 12 months prior to joining the study. To compare the study treatments, the researchers will measure the "duration of episode" (DOE) for each participant. DOE is amount of time it takes for symptoms to disappear and for herpes labialis lesions to heal after taking the study treatment. A doctor will look at the participants' symptom scores and facial images to determine the DOE. Assessments will be done over a period of 14 days.

The participants in this study will apply either acyclovir 50mg buccal tablet or the placebo as a tablet to the upper gum 1 time.

There will be a 2 week treatment phase and a 12 month follow up phase. The participants in this study will not be required to visit the study site. Instead, the participants will have virtual meetings with the study doctors from their homes using the internet. During the treatment phase, there will be 2 meetings. Throughout the follow up phase, the doctors will call the participants 4 times. Each participant will be in the study for about 20 months.

During the treatment phase of the study, the participants will:

• take their blood pressure and pulse
• check their mouth health through a questionnaire
• take pictures of their face and herpes labialis symptoms During the whole study the participants will answer questions about how they are feeling, what medications they are taking, and what adverse events they are having.

The doctors will keep track of any adverse events. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

Participants will be randomly assigned one of two treatment groups - acyclovir 50 mg buccal tablet or a placebo buccal tablet. Face images as well as symptom scores will be recorded at baseline, treatment initiation and over the next 14 days. Participants will automatically transition to the Follow-up Phase. Participants will be in contact with the sites using weekly virtual check-ins with the e-diary/App with the purpose reporting any adverse events, concomitant medications , or new outbreaks of herpes labialis.

Inclusion Criteria:

• Males or females, 18 years of age or older inclusive;

• History of recurrent HL lesions where:

  • Recurrence is defined as at least 4 episodes in the preceding 12 months;
  • At least half of the episodes should be vesicular in nature;
  • At least half of the episodes should be preceded by prodromal symptoms;
  • Herpes labialis lesions are characterized by their localization on the cutaneous and/or mucosal surfaces of the lips;

• Willing to avoid, during the treatment phase, the use of anti-inflammatory (not including low-dose (81 mg) aspirin), anti-herpetic, antibiotic and antiviral agents as well as steroids or other natural products that would interfere with the immune system response;

• Female participants of childbearing potential must be using a medically acceptable form of birth control during screening [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier], abstinence or in same sex relationship and have a negative pregnancy test at Screening and prior to study drug administration. Female participants of non-childbearing potential must be amenorrheic for at least two years or have undergone surgical sterilization (i.e. tubal ligation/occlusion, hysterectomy and/or bilateral oophorectomy);

• Agreement to abstain from any mechanical disruption of the prodromal area or lesion (i.e. scrubbing, lancing, shaving the area, rubbing with alcohol, application of heat emitting devices used for cold sore treatment, etc.);

• Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol;

• Ability to understand and follow study-related instructions;

• Be willing and able to participate in all scheduled visits, treatment plan, and trial procedures according to the clinical protocol.

Exclusion Criteria:

• Participants who did not develop herpes prodromal symptoms within 6 months after randomization in the study;
• More than 50% of recurrences that aborted spontaneously (without intervention) in the past 12 months;
• Primary herpes lesion outside the lips (e.g., nose, chin, etc.);
• Abnormal peri-oral skin condition that might affect the normal course of cold sores (e.g., eczema, psoriasis, etc.);
• Oral diseases whose prodromal symptoms may mimic those of herpes labialis, including recurrent oral aphthous disease;
• Allergy to any acyclovir or its containing agents;
• Milk allergy or known history of hypersensitivity to one of the components of Sitavig;
• Self-reported immunocompromised condition, including self-reported Human Immunodeficiency Virus (HIV) positive and previous bone marrow or organ transplant;
• Known medical history of renal disease, that in the judgment of the investigator is severe;
• Females who are planning to become pregnant, are pregnant or lactating.