HIV Infections, Papillomatosis
Conditions
Keywords
human immunodeficiency virus, human papilloma virus, warts, oral, papillomatosis, treatment experienced
Brief summary
This is a study to test lozenges of interferon-alpha that are dissolved in the mouth as a treatment of oral warts in HIV-positive adults. The hypothesis of this study is that interferon-alpha will be safe and that a higher percentage of subjects given interferon-alpha will experience a complete or nearly complete remission of their oral warts compared to subjects given placebo.
Detailed description
Human papilloma virus (HPV) can cause warts to form in the mouth of infected patients, particularly those with reduced immunity such as people infected with HIV. This is a randomized, double-blind, placebo-controlled trial to determine whether interferon-alpha, delivered in low doses via orally dissolving lozenges, can reduce or eliminate these warts in HIV+ subjects who are receiving combination anti-retroviral therapy (HAART). All potential subjects will have their warts examined and measured at a screening visit. A small amount of one wart (i.e. a biopsy) will be removed for microscopic evaluation to confirm HPV infection and a small amount of blood will be collected for testing. Subjects that qualify for entry will return for a baseline visit at which they will be randomized to active or placebo treatment for 24 weeks. Three out of four subjects will receive active treatment in this study. Subjects must return to the clinic every 6 weeks during treatment to have their warts re-examined. At these follow-up visits, subjects will be asked to complete a brief questionnaire regarding any perceived changes in their warts and their overall mouth condition. A small amount of blood will be taken at the final study visit at week 24 to assess the safety of the interferon lozenges.
Interventions
DRUGInterferon-alpha
500 IU interferon-alpha lozenges taken 3 times per day for 24 weeks
OTHERplacebo
200 mg lozenges containing anhydrous crystalline maltose taken three times per day for 24 weeks
Sponsors
Ainos, Inc. (f/k/a Amarillo Biosciences Inc.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Must have tested positive for HIV. * Must have two or more warts inside the mouth. * Must be receiving a standard course of anti-retroviral therapy (HAART).
Exclusion criteria
* Must not be receiving oral or injected steroids. * Must not be taking other drugs for treatment of oral warts. * Must not have other active HIV-related opportunistic infections.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Oral Mucosal Area Covered by Warts. | 24 weeks, from baseline to the end of treatment | Number of subjects with a 75% or greater decrease from baseline to week 24 in total oral wart area |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject Questionnaire Regarding Global Oral Changes | 24 weeks, from baseline to end of treatment | Number of subjects reporting change in global oral health from baseline to week 24 as better. Scale was subjective with 3 choices: better, worse, or unchanged. |
| Total Surface Area of the Lips Covered by Warts | 24 weeks, from baseline to the end of treatment | Number of subjects with a 75% or greater decrease from baseline to week 24 in total lip wart area |
| Subject Questionnaire Regarding Changes in Warts | 24 weeks, from baseline to the end of treatment | Number of subjects reporting change in oral warts from baseline to week 24 as better. Scale was subjective with 3 choices: better, worse, or unchanged. |
| Investigator Assessment Regarding Changes in Warts | 24 weeks, from baseline to the end of treatment | Number of subjects with improvement in oral warts from baseline to week 24 as rated by the attending investigator. Scale was subjective with 3 choices: improved, worsened, or unchanged. |
| Investigator Assessment Regarding Global Oral Changes. | 24 weeks, from baseline to the end of treatment | Number of subjects with improvement from baseline to week 24 in global oral health as rated by the attending investigator. Scale was subjective with 3 choices: improved, worsened, or unchanged. |
Countries
United States
Participant flow
Recruitment details
Enrollment took place between January 2007 and March 2009 at 10 university-affiliated dental clinics across the US.
Pre-assignment details
All 59 enrolled subjects were randomized to treatment and took at least 1 dose of assigned study drug.
Participants by arm
| Arm | Count |
|---|---|
| IFN Lozenges 500 IU Interferon-alpha lozenges for oral dissolution | 45 |
| Placebo Lozenges 200 mg lozenges containing anhydrous crystalline maltose | 14 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 11 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo Lozenges | IFN Lozenges | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 45 Participants | 59 Participants |
| Age Continuous | 46.6 years STANDARD_DEVIATION 5.43 | 45.0 years STANDARD_DEVIATION 5.05 | 45.4 years STANDARD_DEVIATION 5.14 |
| Region of Enrollment United States | 14 participants | 45 participants | 59 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 13 Participants | 40 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 45 | 3 / 14 |
| serious Total, serious adverse events | 3 / 45 | 1 / 14 |
Outcome results
Primary
Change in Total Oral Mucosal Area Covered by Warts.
Number of subjects with a 75% or greater decrease from baseline to week 24 in total oral wart area
Time frame: 24 weeks, from baseline to the end of treatment
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Lozenges | Change in Total Oral Mucosal Area Covered by Warts. | 11 participants |
| Placebo Lozenges | Change in Total Oral Mucosal Area Covered by Warts. | 2 participants |
Comparison: Chi-square analysis of the proportion of subjects in each group meeting the definition of positive response.p-value: 0.3Chi-squared
Secondary
Investigator Assessment Regarding Changes in Warts
Number of subjects with improvement in oral warts from baseline to week 24 as rated by the attending investigator. Scale was subjective with 3 choices: improved, worsened, or unchanged.
Time frame: 24 weeks, from baseline to the end of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Lozenges | Investigator Assessment Regarding Changes in Warts | 13 participants |
| Placebo Lozenges | Investigator Assessment Regarding Changes in Warts | 5 participants |
Comparison: Chi-square analysis of the proportion of subjects rated as improved with respect to changes in oral warts from baseline to week 24 by the attending investigator.p-value: 0.74Chi-squared
Secondary
Investigator Assessment Regarding Global Oral Changes.
Number of subjects with improvement from baseline to week 24 in global oral health as rated by the attending investigator. Scale was subjective with 3 choices: improved, worsened, or unchanged.
Time frame: 24 weeks, from baseline to the end of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Lozenges | Investigator Assessment Regarding Global Oral Changes. | 9 participants |
| Placebo Lozenges | Investigator Assessment Regarding Global Oral Changes. | 2 participants |
Comparison: Chi-square analysis of the proportion of subjects rated as improved with resepect to changes from baseline to week 24 in global oral health by the attending investigator.p-value: 0.71Chi-squared
Secondary
Subject Questionnaire Regarding Changes in Warts
Number of subjects reporting change in oral warts from baseline to week 24 as better. Scale was subjective with 3 choices: better, worse, or unchanged.
Time frame: 24 weeks, from baseline to the end of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Lozenges | Subject Questionnaire Regarding Changes in Warts | 18 participants |
| Placebo Lozenges | Subject Questionnaire Regarding Changes in Warts | 4 participants |
Comparison: Chi-square analysis of the proportion of subjects in each group reporting change in oral warts from baseline to week 24 as better.p-value: 0.5Chi-squared
Secondary
Subject Questionnaire Regarding Global Oral Changes
Number of subjects reporting change in global oral health from baseline to week 24 as better. Scale was subjective with 3 choices: better, worse, or unchanged.
Time frame: 24 weeks, from baseline to end of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Lozenges | Subject Questionnaire Regarding Global Oral Changes | 14 participants |
| Placebo Lozenges | Subject Questionnaire Regarding Global Oral Changes | 2 participants |
Comparison: Chi-square analysis of the proportion of subjects in each group reporting change in global oral health from baseline to week 24 as better.p-value: 0.29Chi-squared
Secondary
Total Surface Area of the Lips Covered by Warts
Number of subjects with a 75% or greater decrease from baseline to week 24 in total lip wart area
Time frame: 24 weeks, from baseline to the end of treatment
Population: Per protocol - only a sub-set of subjects had lip warts at study entry
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Lozenges | Total Surface Area of the Lips Covered by Warts | 5 participants |
| Placebo Lozenges | Total Surface Area of the Lips Covered by Warts | 0 participants |
Comparison: Chi-square analysis of the proportion of subjects in each group meeting the definition of positive responsep-value: 0.26Chi-squared