Treatment of Oral Warts in HIV+ Patients

• Sponsor: Amarillo Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00454181
• Collaborator: (none)
• Enrollment: 59
• Locations: 12
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Papillomatosis; HIV Infections	Drug: Interferon-alpha; Other: placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluation of Natural Human Interferon Alpha Administered Oromucosally in the Treatment of Oral Warts in HIV-seropositive Subjects Receiving Combination Anti-retroviral Therapy: A Phase 2 Clinical Trial
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IFN lozenges 500 IU Interferon-alpha lozenges for oral dissolution	Drug: Interferon-alpha; 500 IU interferon-alpha lozenges taken 3 times per day for 24 weeks; Other Names: Veldona IFN-alpha lozenge low dose IFN lozenge
Placebo Comparator: placebo lozenges 200 mg lozenges containing anhydrous crystalline maltose	Other: placebo; 200 mg lozenges containing anhydrous crystalline maltose taken three times per day for 24 weeks; Other Names: maltose sugar pill

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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."

3. 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."

4. 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."

5. 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."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, School of Dentistry	San Francisco	California	United States	94143
2	Nova Southeastern University College of Dental Medicine	Fort Lauderdale	Florida	United States	33328-2018
3	Medical College of Georgia School of Dentistry	Augusta	Georgia	United States	30912-1241
4	University of Illinois at Chicago, College of Dentistry	Chicago	Illinois	United States	60612
5	University of Kentucky College of Dentistry	Lexington	Kentucky	United States	40536-0297
6	University of Maryland Baltimore Dental School	Baltimore	Maryland	United States	21201
7	Division of Oral Medicine and Dentistry, Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
8	UMDNJ - New Jersey Dental School	Newark	New Jersey	United States	07108
9	New York University College of Dentistry	New York	New York	United States	10010
10	University of Pennsylvania School of Dental Medicine	Philadelphia	Pennsylvania	United States	19104
11	Baylor College of Dentistry	Dallas	Texas	United States	75246
12	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900

Sponsors and Collaborators

• Amarillo Biosciences, Inc.

Investigators

• Principal Investigator: Deborah Greenspan, BDS, DSc, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Amarillo Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT00454181
• Other Study ID Numbers: 03HUHI19
• First Posted: Mar 30, 2007
• Last Update Posted: Sep 16, 2011
• Last Verified: Sep 1, 2011

• Keywords provided by Amarillo Biosciences, Inc.: human immunodeficiency virus; human papilloma virus; warts, oral; papillomatosis; treatment experienced
• Additional relevant MeSH terms: Papilloma; Interferons; Interferon-alpha

Study Results

Participant Flow

Recruitment Details	Enrollment took place between January 2007 and March 2009 at 10 university-affiliated dental clinics across the US.
Pre-assignment Detail	All 59 enrolled subjects were randomized to treatment and took at least 1 dose of assigned study drug.

Arm/Group Title	IFN Lozenges	Placebo Lozenges
Arm/Group Description	500 IU Interferon-alpha lozenges for oral dissolution	200 mg lozenges containing anhydrous crystalline maltose
Period Title: Overall Study
STARTED	45	14
COMPLETED	30	11
NOT COMPLETED	15	3

Baseline Characteristics

Arm/Group Title	IFN Lozenges	Placebo Lozenges	Total
Arm/Group Description	500 IU Interferon-alpha lozenges for oral dissolution	200 mg lozenges containing anhydrous crystalline maltose	Total of all reporting groups
Overall Participants	45	14	59
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	45 100%	14 100%	59 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.0 (5.05)	46.6 (5.43)	45.4 (5.14)
Sex: Female, Male (Count of Participants)
Female	5 11.1%	1 7.1%	6 10.2%
Male	40 88.9%	13 92.9%	53 89.8%
Region of Enrollment (participants) [Number]
United States	45 100%	14 100%	59 100%

Outcome Measures

1. Primary Outcome

Title	Change in Total Oral Mucosal Area Covered by Warts.
Description	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

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	IFN Lozenges	Placebo Lozenges
Arm/Group Description	500 IU Interferon-alpha lozenges for oral dissolution	200 mg lozenges containing anhydrous crystalline maltose
Measure Participants	36	12
Number [participants]	11 24.4%	2 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IFN Lozenges, Placebo Lozenges
	Comments	Chi-square analysis of the proportion of subjects in each group meeting the definition of positive response.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Total Surface Area of the Lips Covered by Warts
Description	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

Outcome Measure Data

Analysis Population Description

Per protocol - only a sub-set of subjects had lip warts at study entry

Arm/Group Title	IFN Lozenges	Placebo Lozenges
Arm/Group Description	500 IU Interferon-alpha lozenges for oral dissolution	200 mg lozenges containing anhydrous crystalline maltose
Measure Participants	13	4
Number [participants]	5 11.1%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IFN Lozenges, Placebo Lozenges
	Comments	Chi-square analysis of the proportion of subjects in each group meeting the definition of positive response
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Subject Questionnaire Regarding Changes in Warts
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IFN Lozenges	Placebo Lozenges
Arm/Group Description	500 IU Interferon-alpha lozenges for oral dissolution	200 mg lozenges containing anhydrous crystalline maltose
Measure Participants	36	12
Number [participants]	18 40%	4 28.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IFN Lozenges, Placebo Lozenges
	Comments	Chi-square analysis of the proportion of subjects in each group reporting change in oral warts from baseline to week 24 as "better."
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Subject Questionnaire Regarding Global Oral Changes
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IFN Lozenges	Placebo Lozenges
Arm/Group Description	500 IU Interferon-alpha lozenges for oral dissolution	200 mg lozenges containing anhydrous crystalline maltose
Measure Participants	36	12
Number [participants]	14 31.1%	2 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IFN Lozenges, Placebo Lozenges
	Comments	Chi-square analysis of the proportion of subjects in each group reporting change in global oral health from baseline to week 24 as "better."
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Investigator Assessment Regarding Changes in Warts
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IFN Lozenges	Placebo Lozenges
Arm/Group Description	500 IU Interferon-alpha lozenges for oral dissolution	200 mg lozenges containing anhydrous crystalline maltose
Measure Participants	36	12
Number [participants]	13 28.9%	5 35.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IFN Lozenges, Placebo Lozenges
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Investigator Assessment Regarding Global Oral Changes.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IFN Lozenges	Placebo Lozenges
Arm/Group Description	500 IU Interferon-alpha lozenges for oral dissolution	200 mg lozenges containing anhydrous crystalline maltose
Measure Participants	36	12
Number [participants]	9 20%	2 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IFN Lozenges, Placebo Lozenges
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.71
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	6 months
Arm/Group Title	IFN Lozenges		Placebo Lozenges
Arm/Group Description	500 IU Interferon-alpha lozenges for oral dissolution		200 mg lozenges containing anhydrous crystalline maltose
All Cause Mortality
	IFN Lozenges		Placebo Lozenges
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IFN Lozenges		Placebo Lozenges
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/45 (6.7%)		1/14 (7.1%)
Gastrointestinal disorders
esophageal ulcer	1/45 (2.2%)	1	0/14 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
anal cancer	0/45 (0%)	0	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
pneumonia	2/45 (4.4%)	2	0/14 (0%)	0
asthma	1/45 (2.2%)	1	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	IFN Lozenges		Placebo Lozenges
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/45 (15.6%)		3/14 (21.4%)
Gastrointestinal disorders
diarrhea	3/45 (6.7%)	3	0/14 (0%)	0
Infections and infestations
candidiasis	3/45 (6.7%)	5	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
upper respiratory tract infection	1/45 (2.2%)	1	2/14 (14.3%)	2
Surgical and medical procedures
tooth extraction	3/45 (6.7%)	3	0/14 (0%)	0

Limitations/Caveats

Only 59 of 80 planned subjects were randomized, so statistical power of the study was limited.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.