Recurrent Herpes Labialis
Conditions
Keywords
Herpes Labialis, Cold Sore
Brief summary
The purpose of this study is to determine if Merlin, a mixture of ethanol and glycolic acid, is safe and effective in the treatment of cold sores. Subjects who meet the requirements to participate in the study will be put randomly, and equally, into one of two groups: 1) a group receiving Merlin to treat their cold sore; or 2)a group receiving a placebo of just ethanol to treat their cold sore. Neither the subject nor the site will know which treatment they will be getting. Once the subject has been assigned to a treatment group, they will be given a kit containing a bottle of the treatment and special swabs to apply the liquid. The subject will be told to take the kit home and wait until they think they are starting to get a cold sore. Once a subject begins to see something that they think is the start of a cold sore, they are to immediately call the clinic. Once the clinic confirms that the subject is in fact starting to get a cold sore, the subject will be told to open the kit and begin treatment. From the start of treatment, there will be twelve (12) treatments, with either Merlin or placebo, applied six (6) hours apart, up to 3 per day, over the next 96 hours (4 days). Each treatment of Merlin or placebo is made up of three (3) applications given twenty (20) minutes apart, for a total of thirty-six (36) applications. For each application, the subject will use the special swab to put the Merlin or placebo solution on their cold sore. Subjects will need to report daily to the clinic for a minimum of 3 consecutive days, until either the cold sore is completely healed or 14 days from the start of treatment, whichever comes first. At each clinic visit the cold sore will be observed to determine at what stage it is at or if it has healed. The subject will also be asked how they are feeling. Subjects will also be told to record in a diary the time of each application of Merlin or placebo. They will also be asked to record the stage of their lesion and how much pain, if any, related to the cold sore, that they are feeling.
Interventions
DRUGMerlin
glycolic acid/ethanol solution
DRUGEthanol
Ethanol solution
Sponsors
Benu BioPharma, LLC
Accelovance
Optimal Research
Topical Remedy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subject 18-75 years of age * Female subjects must be using a medically acceptable form of birth control during the study. Acceptable birth control measures include, but are not limited to: abstinence, oral contraceptive pills or patch, injectable contraception, barrier contraceptives (condom, diaphragm with spermicide), IUD, vaginal contraceptive ring, surgical (hysterectomy, tubal ligation), vasectomized partner, and natural post-menopausal inability to conceive. Menopause is defined for this protocol as starting one year after the time of the last menstrual period. * Subject must have a history of recurrent herpes labialis and report at least 3 separate recurrences (i.e. multiple herpetic lesions in one outbreak count as only one episode) during the preceding 12 months. * Subject must have a history of experiencing prodromal symptoms of cold sores (e.g. itching, tingling, or burning) during at least half of their previous cold sore episodes. * Subject must have a history of at least half of their cold sore episodes producing classical lesions (i.e., episodes that progressed through macule, papule, vesicle, crust, and healed). * Subject must provide voluntary written informed consent to participate in this study. * Subject is able to appear for a clinic visit within 24 hours from the time of treating cold sore and is able to return to the clinic for the full 14 day duration of the study if necessary.
Exclusion criteria
* Subjects with evidence of active malignancy or immunodeficiency disease within the last 30 days. Subjects who have completed therapy and are considered unlikely to relapse or who have had surgery and do not have any evidence of disease, are eligible for the study. * Subject requires chronic use of immunomodifying drugs (e.g. systemic steroids) or topical steroids on or near the face; use of inhaled steroids does not exclude a subject from the study. If a subject is unlikely to get through the Treatment Phase of the protocol without requiring the use of an immunomodifying drug for a chronic condition the subject should be excluded. * Subject requires chronic use of anti-viral medication. In females of childbearing potential, a positive urine pregnancy test at time of screening. Nursing mothers. * Subject has abnormal skin conditions (e.g. acne, eczema, rosacea, psoriasis, albinism, or chronic vesiculobullous disorders) that occur in the area ordinarily affected by cold sores or has significant facial hair in the area of the cold sore that might affect the normal course of the cold sore or might impair accurate evaluation of the cold sore lesion. * Subject has had a vaccine for herpes simplex virus type 1 (typically oral herpes) or 2 (typically genital herpes). * Subject is currently enrolled in another clinical trial involving the use of a drug and/or a device. * Subject requires chronic use of analgesics or non-steroidal anti-inflammatory agents (NSAIDs) except for low doses of aspirin (less than 325 mg/day) used for cardiovascular purposes. If a subject is unlikely to get through the Treatment Phase of the protocol without requiring the use of analgesia for a chronic condition, e.g. back pain, recurrent daily headaches, the subject should be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician Assessed Duration of the Classical Herpetic Lesion | From time of beginning of treatment until onset of Lesion Stage 6 or Stage 7, if Stage 6 never observed, with a maximum of 14 days. | The time in hours from beginning of treatment to onset of Stage 6 (residual swelling) or Stage 7 (complete healing) if Stage 6 never observed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinician Assessed Duration Until Complete Healing of the Herpetic Episode | From the beginning of treatment to onset of Stage 7 - maximum of 14 days | The time, in hours, from the beginning of treatment to onset of Stage 7 |
| Clinician Assessed Prevention of Progression to Classical Lesion | 14 days maximum | Proportion of subjects in each treatment group who do not display classical lesions |
| Clinician Assessed Duration of the Herpetic Episode | For classical lesions: from the beginning of the treatment until loss of hard crust (Stage 6); for non-classical lesions the time from the beginning of treatment until complete resolution of all local signs and symptoms (Stage 7) - maximum of 14 days | For classical lesions: the time in hours from the beginning of the treatment until loss of hard crust (Stage 6); for non-classical lesions the time from the beginning of treatment until complete resolution of all local signs and symptoms (Stage 7) |
| Clinician Assessed Duration of the Herpetic Lesion Hard Scab | From start of Stage 5 to loss of hard crust - maximum of 14 days | Duration of the hard crust (Stage 5) |
| Subject Assessed Duration of Pain | From time of first occurrence of at least mild pain to time of consistent scoring of no pain - maximum 14 days | Time of first occurrence of at least mild pain to consistent scoring of no pain |
| Clinician Assessed Lesion Size | 14 days maximum | Maximum lesion area for ulcerative lesions during Stages 3-5 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Merlin glycolic acid and ethanol mixture
Merlin: glycolic acid/ethanol solution | 227 |
| Ethanol Ethanol: Ethanol solution | 224 |
| Total | 451 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not treat cold sore during study | 149 | 143 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Ethanol | Total | Merlin |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 6 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 77 Participants | 150 Participants | 73 Participants |
| Age, Continuous | 42.7 Years STANDARD_DEVIATION 12.8 | 42.1 Years STANDARD_DEVIATION 12.32 | 41.4 Years STANDARD_DEVIATION 11.84 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 66 Participants | 134 Participants | 68 Participants |
| Region of Enrollment United States | 80 participants | 156 participants | 76 participants |
| Sex: Female, Male Female | 62 Participants | 118 Participants | 56 Participants |
| Sex: Female, Male Male | 18 Participants | 38 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 80 |
| other Total, other adverse events | 10 / 76 | 4 / 80 |
| serious Total, serious adverse events | 0 / 76 | 0 / 80 |
Outcome results
Primary
Clinician Assessed Duration of the Classical Herpetic Lesion
The time in hours from beginning of treatment to onset of Stage 6 (residual swelling) or Stage 7 (complete healing) if Stage 6 never observed
Time frame: From time of beginning of treatment until onset of Lesion Stage 6 or Stage 7, if Stage 6 never observed, with a maximum of 14 days.
Population: Only those subjects who developed a classical cold sore lesion, i.e. exhibited Stages 3, 4 or 5, during the course of the trial and treated were analyzed for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Merlin | Clinician Assessed Duration of the Classical Herpetic Lesion | 162.7 hours | Standard Deviation 68.4 |
| Ethanol | Clinician Assessed Duration of the Classical Herpetic Lesion | 163.6 hours | Standard Deviation 74.9 |
Secondary
Clinician Assessed Duration of the Herpetic Episode
For classical lesions: the time in hours from the beginning of the treatment until loss of hard crust (Stage 6); for non-classical lesions the time from the beginning of treatment until complete resolution of all local signs and symptoms (Stage 7)
Time frame: For classical lesions: from the beginning of the treatment until loss of hard crust (Stage 6); for non-classical lesions the time from the beginning of treatment until complete resolution of all local signs and symptoms (Stage 7) - maximum of 14 days
Population: Subjects who developed a cold sore lesion and treated during the course of the trial. One subject in the Merlin cohort was lost to follow-up, did not complete the study and was therefore excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Merlin | Clinician Assessed Duration of the Herpetic Episode | 151.1 hours | Standard Deviation 70.9 |
| Ethanol | Clinician Assessed Duration of the Herpetic Episode | 158.6 hours | Standard Deviation 74.5 |
Secondary
Clinician Assessed Duration of the Herpetic Lesion Hard Scab
Duration of the hard crust (Stage 5)
Time frame: From start of Stage 5 to loss of hard crust - maximum of 14 days
Population: Only those subjects who developed a cold sore with a hard scab (Stage 5) were analyzed for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Merlin | Clinician Assessed Duration of the Herpetic Lesion Hard Scab | 66.6 hours | Standard Deviation 56.8 |
| Ethanol | Clinician Assessed Duration of the Herpetic Lesion Hard Scab | 65.9 hours | Standard Deviation 62.3 |
Secondary
Clinician Assessed Duration Until Complete Healing of the Herpetic Episode
The time, in hours, from the beginning of treatment to onset of Stage 7
Time frame: From the beginning of treatment to onset of Stage 7 - maximum of 14 days
Population: Subjects who developed a cold sore and treated during the course of the trial. One subject in the Merlin cohort was lost to follow-up, did not complete the study and was therefore excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Merlin | Clinician Assessed Duration Until Complete Healing of the Herpetic Episode | 223.4 hours | Standard Deviation 83.2 |
| Ethanol | Clinician Assessed Duration Until Complete Healing of the Herpetic Episode | 222.0 hours | Standard Deviation 86.4 |
Secondary
Clinician Assessed Lesion Size
Maximum lesion area for ulcerative lesions during Stages 3-5
Time frame: 14 days maximum
Population: Subjects who developed a classical herpetic lesion during the course of the trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Merlin | Clinician Assessed Lesion Size | 46.8 square mm | Standard Deviation 50.2 |
| Ethanol | Clinician Assessed Lesion Size | 36.2 square mm | Standard Deviation 43.7 |
Secondary
Clinician Assessed Prevention of Progression to Classical Lesion
Proportion of subjects in each treatment group who do not display classical lesions
Time frame: 14 days maximum
Population: Subjects who developed a cold sore lesion and treated during the course of the trial. One subject in the Merlin cohort was lost to follow-up, did not complete the study and was therefore excluded from this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Merlin | Clinician Assessed Prevention of Progression to Classical Lesion | 12 Participants |
| Ethanol | Clinician Assessed Prevention of Progression to Classical Lesion | 6 Participants |
Secondary
Subject Assessed Duration of Pain
Time of first occurrence of at least mild pain to consistent scoring of no pain
Time frame: From time of first occurrence of at least mild pain to time of consistent scoring of no pain - maximum 14 days
Population: Subjects with cold sore lesions pain assessment. One subject in the Merlin cohort was lost to follow-up, did not complete the study and was therefore excluded from this analysis.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Merlin | Subject Assessed Duration of Pain | Fourth Treatment | No Pain | 31 Participants |
| Merlin | Subject Assessed Duration of Pain | Tenth Treatment | Moderate | 5 Participants |
| Merlin | Subject Assessed Duration of Pain | Max Severity Post Treatment | Moderate | 9 Participants |
| Merlin | Subject Assessed Duration of Pain | First Treatment | No Pain | 31 Participants |
| Merlin | Subject Assessed Duration of Pain | First Treatment | Mild | 40 Participants |
| Merlin | Subject Assessed Duration of Pain | First Treatment | Moderate | 4 Participants |
| Merlin | Subject Assessed Duration of Pain | First Treatment | Severe | 0 Participants |
| Merlin | Subject Assessed Duration of Pain | Second Treatment | No Pain | 33 Participants |
| Merlin | Subject Assessed Duration of Pain | Second Treatment | Mild | 30 Participants |
| Merlin | Subject Assessed Duration of Pain | Second Treatment | Moderate | 12 Participants |
| Merlin | Subject Assessed Duration of Pain | Second Treatment | Severe | 0 Participants |
| Merlin | Subject Assessed Duration of Pain | Third Treatment | No Pain | 29 Participants |
| Merlin | Subject Assessed Duration of Pain | Third Treatment | Mild | 28 Participants |
| Merlin | Subject Assessed Duration of Pain | Third Treatment | Moderate | 18 Participants |
| Merlin | Subject Assessed Duration of Pain | Third Treatment | Severe | 0 Participants |
| Merlin | Subject Assessed Duration of Pain | Fourth Treatment | Mild | 30 Participants |
| Merlin | Subject Assessed Duration of Pain | Fourth Treatment | Moderate | 11 Participants |
| Merlin | Subject Assessed Duration of Pain | Fourth Treatment | Severe | 1 Participants |
| Merlin | Subject Assessed Duration of Pain | Fifth Treatment | No Pain | 33 Participants |
| Merlin | Subject Assessed Duration of Pain | Fifth Treatment | Mild | 30 Participants |
| Merlin | Subject Assessed Duration of Pain | Fifth Treatment | Moderate | 9 Participants |
| Merlin | Subject Assessed Duration of Pain | Fifth Treatment | Severe | 1 Participants |
| Merlin | Subject Assessed Duration of Pain | Sixth Treatment | No Pain | 38 Participants |
| Merlin | Subject Assessed Duration of Pain | Sixth Treatment | Mild | 23 Participants |
| Merlin | Subject Assessed Duration of Pain | Sixth Treatment | Moderate | 9 Participants |
| Merlin | Subject Assessed Duration of Pain | Sixth Treatment | Severe | 2 Participants |
| Merlin | Subject Assessed Duration of Pain | Seventh Treatment | No Pain | 38 Participants |
| Merlin | Subject Assessed Duration of Pain | Seventh Treatment | Mild | 16 Participants |
| Merlin | Subject Assessed Duration of Pain | Seventh Treatment | Moderate | 10 Participants |
| Merlin | Subject Assessed Duration of Pain | Seventh Treatment | Severe | 1 Participants |
| Merlin | Subject Assessed Duration of Pain | Eighth Treatment | No Pain | 40 Participants |
| Merlin | Subject Assessed Duration of Pain | Eighth Treatment | Mild | 10 Participants |
| Merlin | Subject Assessed Duration of Pain | Eighth Treatment | Moderate | 7 Participants |
| Merlin | Subject Assessed Duration of Pain | Eighth Treatment | Severe | 2 Participants |
| Merlin | Subject Assessed Duration of Pain | Ninth Treatment | No Pain | 38 Participants |
| Merlin | Subject Assessed Duration of Pain | Ninth Treatment | Mild | 10 Participants |
| Merlin | Subject Assessed Duration of Pain | Ninth Treatment | Moderate | 5 Participants |
| Merlin | Subject Assessed Duration of Pain | Ninth Treatment | Severe | 2 Participants |
| Merlin | Subject Assessed Duration of Pain | Tenth Treatment | No Pain | 32 Participants |
| Merlin | Subject Assessed Duration of Pain | Tenth Treatment | Mild | 11 Participants |
| Merlin | Subject Assessed Duration of Pain | Tenth Treatment | Severe | 3 Participants |
| Merlin | Subject Assessed Duration of Pain | Eleventh Treatment | No Pain | 32 Participants |
| Merlin | Subject Assessed Duration of Pain | Eleventh Treatment | Mild | 9 Participants |
| Merlin | Subject Assessed Duration of Pain | Eleventh Treatment | Moderate | 4 Participants |
| Merlin | Subject Assessed Duration of Pain | Eleventh Treatment | Severe | 2 Participants |
| Merlin | Subject Assessed Duration of Pain | Twelfth Treatment | No Pain | 33 Participants |
| Merlin | Subject Assessed Duration of Pain | Twelfth Treatment | Mild | 9 Participants |
| Merlin | Subject Assessed Duration of Pain | Twelfth Treatment | Moderate | 2 Participants |
| Merlin | Subject Assessed Duration of Pain | Twelfth Treatment | Severe | 1 Participants |
| Merlin | Subject Assessed Duration of Pain | Max Severity Post Treatment | No Pain | 45 Participants |
| Merlin | Subject Assessed Duration of Pain | Max Severity Post Treatment | Mild | 14 Participants |
| Merlin | Subject Assessed Duration of Pain | Max Severity Post Treatment | Severe | 2 Participants |
| Ethanol | Subject Assessed Duration of Pain | Seventh Treatment | No Pain | 31 Participants |
| Ethanol | Subject Assessed Duration of Pain | Fourth Treatment | No Pain | 35 Participants |
| Ethanol | Subject Assessed Duration of Pain | Tenth Treatment | Mild | 22 Participants |
| Ethanol | Subject Assessed Duration of Pain | Twelfth Treatment | Mild | 15 Participants |
| Ethanol | Subject Assessed Duration of Pain | Seventh Treatment | Mild | 29 Participants |
| Ethanol | Subject Assessed Duration of Pain | First Treatment | No Pain | 35 Participants |
| Ethanol | Subject Assessed Duration of Pain | Tenth Treatment | Severe | 0 Participants |
| Ethanol | Subject Assessed Duration of Pain | Seventh Treatment | Moderate | 5 Participants |
| Ethanol | Subject Assessed Duration of Pain | First Treatment | Mild | 37 Participants |
| Ethanol | Subject Assessed Duration of Pain | Max Severity Post Treatment | Severe | 3 Participants |
| Ethanol | Subject Assessed Duration of Pain | First Treatment | Moderate | 7 Participants |
| Ethanol | Subject Assessed Duration of Pain | Seventh Treatment | Severe | 0 Participants |
| Ethanol | Subject Assessed Duration of Pain | First Treatment | Severe | 0 Participants |
| Ethanol | Subject Assessed Duration of Pain | Eleventh Treatment | No Pain | 31 Participants |
| Ethanol | Subject Assessed Duration of Pain | Second Treatment | No Pain | 32 Participants |
| Ethanol | Subject Assessed Duration of Pain | Eighth Treatment | No Pain | 30 Participants |
| Ethanol | Subject Assessed Duration of Pain | Second Treatment | Mild | 40 Participants |
| Ethanol | Subject Assessed Duration of Pain | Twelfth Treatment | Moderate | 4 Participants |
| Ethanol | Subject Assessed Duration of Pain | Second Treatment | Moderate | 7 Participants |
| Ethanol | Subject Assessed Duration of Pain | Eighth Treatment | Mild | 24 Participants |
| Ethanol | Subject Assessed Duration of Pain | Second Treatment | Severe | 1 Participants |
| Ethanol | Subject Assessed Duration of Pain | Eleventh Treatment | Mild | 16 Participants |
| Ethanol | Subject Assessed Duration of Pain | Third Treatment | No Pain | 32 Participants |
| Ethanol | Subject Assessed Duration of Pain | Eighth Treatment | Moderate | 5 Participants |
| Ethanol | Subject Assessed Duration of Pain | Third Treatment | Mild | 38 Participants |
| Ethanol | Subject Assessed Duration of Pain | Max Severity Post Treatment | Mild | 20 Participants |
| Ethanol | Subject Assessed Duration of Pain | Third Treatment | Moderate | 7 Participants |
| Ethanol | Subject Assessed Duration of Pain | Eighth Treatment | Severe | 0 Participants |
| Ethanol | Subject Assessed Duration of Pain | Third Treatment | Severe | 3 Participants |
| Ethanol | Subject Assessed Duration of Pain | Eleventh Treatment | Moderate | 5 Participants |
| Ethanol | Subject Assessed Duration of Pain | Fourth Treatment | Mild | 35 Participants |
| Ethanol | Subject Assessed Duration of Pain | Ninth Treatment | No Pain | 31 Participants |
| Ethanol | Subject Assessed Duration of Pain | Fourth Treatment | Moderate | 6 Participants |
| Ethanol | Subject Assessed Duration of Pain | Twelfth Treatment | Severe | 0 Participants |
| Ethanol | Subject Assessed Duration of Pain | Fourth Treatment | Severe | 2 Participants |
| Ethanol | Subject Assessed Duration of Pain | Ninth Treatment | Mild | 19 Participants |
| Ethanol | Subject Assessed Duration of Pain | Fifth Treatment | No Pain | 34 Participants |
| Ethanol | Subject Assessed Duration of Pain | Eleventh Treatment | Severe | 0 Participants |
| Ethanol | Subject Assessed Duration of Pain | Fifth Treatment | Mild | 30 Participants |
| Ethanol | Subject Assessed Duration of Pain | Ninth Treatment | Moderate | 5 Participants |
| Ethanol | Subject Assessed Duration of Pain | Fifth Treatment | Moderate | 9 Participants |
| Ethanol | Subject Assessed Duration of Pain | Max Severity Post Treatment | Moderate | 8 Participants |
| Ethanol | Subject Assessed Duration of Pain | Fifth Treatment | Severe | 1 Participants |
| Ethanol | Subject Assessed Duration of Pain | Ninth Treatment | Severe | 0 Participants |
| Ethanol | Subject Assessed Duration of Pain | Sixth Treatment | No Pain | 33 Participants |
| Ethanol | Subject Assessed Duration of Pain | Twelfth Treatment | No Pain | 32 Participants |
| Ethanol | Subject Assessed Duration of Pain | Sixth Treatment | Mild | 28 Participants |
| Ethanol | Subject Assessed Duration of Pain | Tenth Treatment | No Pain | 26 Participants |
| Ethanol | Subject Assessed Duration of Pain | Sixth Treatment | Moderate | 9 Participants |
| Ethanol | Subject Assessed Duration of Pain | Max Severity Post Treatment | No Pain | 47 Participants |
| Ethanol | Subject Assessed Duration of Pain | Sixth Treatment | Severe | 0 Participants |
| Ethanol | Subject Assessed Duration of Pain | Tenth Treatment | Moderate | 3 Participants |