External Genital Warts
Conditions
Keywords
External Genital Warts, Sinecatechins, Cryotherapy
Brief summary
External Genital Warts (EGW) are the most common sexually transmitted disease associated with more than 30 types of the Human Papillomavirus (HPV). Cryotherapy is an effective method of EGW treatment. However, multiple sessions may be required with reported clearance rates ranging between 27-88%. Sinecatechins 15% ointment is Food and Drug Administration approved for three times daily application in immunocompetent subjects 18 years and older for the treatment of EGW and perianal warts. Treatment of EGW with cryotherapy followed by sinecatechins appears to be logical. Cryotherapy has direct cytodestructive effects with immediate short-term efficacy on treated EGW, while sinecatechins provide field therapy, treating both clinical and sub-clinical lesions. For this study, the investigators used sinecatechins 15% ointment twice daily regimen and anticipated that the synergistic effect with cryotherapy will provide better efficacy that cryotherapy alone. The investigators also anticipated that the sequential therapy with be safe.
Detailed description
A total of 42 subjects received standardized cryotherapy to all lesions, using two cycles of five seconds each, separated by a five second interval rest (Week 0/Baseline). One week following cryotherapy, subjects were randomized 1:1 to either additional treatment with sinecatechins 15% ointment twice daily or no additional treatment. Those subjects randomized to additional treatment received sinecatechins 15% ointment BID for up to sixteen weeks, or until complete clearance of all EGW, whichever occurred first. Additionally, subjects were advised to maintain safe sexual practices and have all recent sexual partners examined for EGW. Subjects were followed every 8 weeks for a total of 16 weeks (Table 1). EGW lesion counts were conducted at all study visits by the same qualified blinded evaluator. Additionally, at each visit local skin reactions, change in concomitant medications, and adverse events were assessed. Any subjects who received sinecatechins 15% ointment and discontinued prematurely were asked to return for an End of Study Visit. Females of childbearing potential underwent a urine pregnant test at all visits during study treatment period. Subjects that met complete responder criteria as above, were additionally followed and assessed at Visit5/Week 41 and Visit 6/Week 65 to assess for wart recurrence.
Interventions
DRUGSinecatechins 15% Ointment
Following cryotherapy, half of the subjects will be randomized to treatment with sinecatechins ointment twice daily starting one week after cryotherapy (Week 1).
Cryotherapy will be standardized in all subjects and for all treated lesions.
Sponsors
Fougera Pharmaceuticals Inc.
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults at least 18 years old with at least two visible EGWs. * Subject must be in good general health as confirmed by the medical history. * Subject must be able to read, sign, and understand the informed consent. * Subject must be willing to forego any other treatments for his/her EGW lesions. * Subject is willing and able to participate in the study as an outpatient, making frequent visits to the study center during the treatment and follow-up periods and to comply with all study requirements including concomitant medication and other treatment restrictions. * If subject is a female of childbearing potential she must have a negative urine pregnancy test result prior to study treatment initiation and must agree to use an approved method of birth control while enrolled in the study.
Exclusion criteria
* Subject with any evidence of herpes genitalis or any other current and/or recurrent genital or uncontrolled infection, including Human Immunodeficiency Virus, Hepatitis B or Hepatitis C. * Subject with an unstable medical condition as deemed by the clinical investigator. * Subject with any dermatologic disease in the treatment area that may be exacerbated by the treatment proposed or that might impair the evaluation of EGW lesions. * Subject who has previously been treated in an EGW clinical trial, had treatment of anogenital warts or had systemic intake of virostatics or immunosuppressive medication within 30 days prior to Baseline Visit. * Women who are pregnant, lactating, or planning to become pregnant during the study period. * Subject who have experienced a clinically important medical event within 90 days of the visit (e.g., stroke, myocardial infarction, etc). * Subject who have active chemical dependency or alcoholism as assessed by the investigator. * Subject who have known allergies to any component of the study ointment. * Subject who have organ allograft, skin conditions that may interfere with study ointment, or having internal (vaginal or rectal) warts that have required treatment. * Subject who has received any of the following within 90 days prior to study treatment initiation: * interferon or interferon inducers * cytotoxic drugs * immunomodulators or immunosuppressive therapies (inhaled/ intranasal corticosteroids are permitted) * oral or parenteral corticosteroids * topical corticosteroids if greater than 2 gm/day * any dermatologic procedures or surgeries on the study area (including any EGW treatments) * Subject who have used any topical prescription medications on the study area within 30 days prior to study treatment initiation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Clearance, | at week 1, week 9, and week 17 | Subjects with complete clearance, or no longer have HPV infected cells. Complete clearance was defined as zero lesions at the respective time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Recurrence of Previously Treated EGW Lesions | at 24 week post-treatment period | To evaluate the efficacy of using combination cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone on EGW lesions via recurrence rates of previously treated EGW lesions in those subjects who achieved a complete response over a 24 week post-treatment period. |
| Local Skin Reactions | at 16 week treatment period | To evaluate the safety of cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone as a regimen for EGW by evaluating for local skin reactions and adverse events. Number of participants with local skin reactions. |
| Subjects With Partial Clearance of Lesions | At week 1, week 9, and week 17 | Partial clearance is described as at least 50% reduction from baseline |
| Mean Change in Number of Lesions | Week 1, week 9 and week 17 | Mean change in number of lesions after 1 weeks, 9 weeks and 17 weeks post treatment as compared to baseline |
Countries
United States
Participant flow
Recruitment details
All patients were enrolled from September 2011 to December 2012.
Participants by arm
| Arm | Count |
|---|---|
| Sinecatechins 15% Ointment and Cryotherapy Sinecatechins 15% Ointment: Following cryotherapy, half of the subjects randomized to treatment with sinecatechins ointment twice daily starting one week after cryotherapy up to 16 weeks or until complete clearance. | 21 |
| Cryotherapy Alone Cryotherapy standardized in all subjects and for all treated lesions: EGW lesions treated with 2 cycles, 5 seconds each, with a 5 second interval. All subjects treated with the same cryo-spray regimen. | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | medication noncompliance | 3 | 0 |
| Overall Study | unable to make visits | 4 | 0 |
Baseline characteristics
| Characteristic | Cryotherapy Alone | Sinecatechins 15% Ointment and Cryotherapy | Total |
|---|---|---|---|
| Age, Continuous | 35.8 years STANDARD_DEVIATION 4.4 | 38.8 years STANDARD_DEVIATION 5.2 | 37.3 years STANDARD_DEVIATION 4.8 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 18 Participants | 17 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 21 / 21 | 21 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Number of Participants With Complete Clearance,
Subjects with complete clearance, or no longer have HPV infected cells. Complete clearance was defined as zero lesions at the respective time points.
Time frame: at week 1, week 9, and week 17
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sinecatechins 15% Ointment & Cryotherapy | Number of Participants With Complete Clearance, | at week 17 | 6 participants |
| Sinecatechins 15% Ointment & Cryotherapy | Number of Participants With Complete Clearance, | at week 1 | 0 participants |
| Sinecatechins 15% Ointment & Cryotherapy | Number of Participants With Complete Clearance, | at week 9 | 3 participants |
| Cryotherapy Alone | Number of Participants With Complete Clearance, | at week 17 | 6 participants |
| Cryotherapy Alone | Number of Participants With Complete Clearance, | at week 9 | 5 participants |
| Cryotherapy Alone | Number of Participants With Complete Clearance, | at week 1 | 0 participants |
Secondary
Local Skin Reactions
To evaluate the safety of cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone as a regimen for EGW by evaluating for local skin reactions and adverse events. Number of participants with local skin reactions.
Time frame: at 16 week treatment period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sinecatechins 15% Ointment & Cryotherapy | Local Skin Reactions | 21 Participants |
| Cryotherapy Alone | Local Skin Reactions | 21 Participants |
Secondary
Mean Change in Number of Lesions
Mean change in number of lesions after 1 weeks, 9 weeks and 17 weeks post treatment as compared to baseline
Time frame: Week 1, week 9 and week 17
Population: data for only those participants who returned for the respective visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sinecatechins 15% Ointment & Cryotherapy | Mean Change in Number of Lesions | Week 1 | -2.2 number of lesions | Standard Deviation 3.93 |
| Sinecatechins 15% Ointment & Cryotherapy | Mean Change in Number of Lesions | Week 9 | -5.4 number of lesions | Standard Deviation 5.71 |
| Sinecatechins 15% Ointment & Cryotherapy | Mean Change in Number of Lesions | Week 17 | -4.8 number of lesions | Standard Deviation 7.87 |
| Cryotherapy Alone | Mean Change in Number of Lesions | Week 1 | -2.1 number of lesions | Standard Deviation 3.83 |
| Cryotherapy Alone | Mean Change in Number of Lesions | Week 9 | -2.7 number of lesions | Standard Deviation 3.68 |
| Cryotherapy Alone | Mean Change in Number of Lesions | Week 17 | -3.8 number of lesions | Standard Deviation 5.49 |
Secondary
Mean Change in Number of Lesions
Mean change in number of lesions as compared to baseline at Week 1, Week 9 and Week 17 for the intent-to-treat population
Time frame: At week 1, week 9, and week 17
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sinecatechins 15% Ointment & Cryotherapy | Mean Change in Number of Lesions | Week 1 | -2.2 lesions | Standard Deviation 3.93 |
| Sinecatechins 15% Ointment & Cryotherapy | Mean Change in Number of Lesions | Week 9 | -5.0 lesions | Standard Deviation 5.74 |
| Sinecatechins 15% Ointment & Cryotherapy | Mean Change in Number of Lesions | Week 17 | -5.0 lesions | Standard Deviation 6.9 |
| Cryotherapy Alone | Mean Change in Number of Lesions | Week 1 | -2.1 lesions | Standard Deviation 3.83 |
| Cryotherapy Alone | Mean Change in Number of Lesions | Week 9 | -2.1 lesions | Standard Deviation 3.75 |
| Cryotherapy Alone | Mean Change in Number of Lesions | Week 17 | -2.1 lesions | Standard Deviation 4.73 |
Secondary
Number of Participants With Recurrence of Previously Treated EGW Lesions
To evaluate the efficacy of using combination cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone on EGW lesions via recurrence rates of previously treated EGW lesions in those subjects who achieved a complete response over a 48 week post-treatment period.
Time frame: at 48 week post-treatment period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sinecatechins 15% Ointment & Cryotherapy | Number of Participants With Recurrence of Previously Treated EGW Lesions | 2 Participants |
| Cryotherapy Alone | Number of Participants With Recurrence of Previously Treated EGW Lesions | 6 Participants |
Secondary
Number of Participants With Recurrence of Previously Treated EGW Lesions
To evaluate the efficacy of using combination cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone on EGW lesions via recurrence rates of previously treated EGW lesions in those subjects who achieved a complete response over a 24 week post-treatment period.
Time frame: at 24 week post-treatment period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sinecatechins 15% Ointment & Cryotherapy | Number of Participants With Recurrence of Previously Treated EGW Lesions | 1 Participants |
| Cryotherapy Alone | Number of Participants With Recurrence of Previously Treated EGW Lesions | 5 Participants |
Secondary
Subjects With Partial Clearance of Lesions
Partial clearance is described as at least 50% reduction from baseline
Time frame: At week 1, week 9, and week 17
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sinecatechins 15% Ointment & Cryotherapy | Subjects With Partial Clearance of Lesions | at week 1 | 7 participants |
| Sinecatechins 15% Ointment & Cryotherapy | Subjects With Partial Clearance of Lesions | at week 9 | 15 participants |
| Sinecatechins 15% Ointment & Cryotherapy | Subjects With Partial Clearance of Lesions | at week 17 | 15 participants |
| Cryotherapy Alone | Subjects With Partial Clearance of Lesions | at week 1 | 6 participants |
| Cryotherapy Alone | Subjects With Partial Clearance of Lesions | at week 9 | 9 participants |
| Cryotherapy Alone | Subjects With Partial Clearance of Lesions | at week 17 | 11 participants |