Vaccine Therapy in Preventing HPV in HIV-Positive Women in India

• Sponsor: AIDS Malignancy Consortium (Other)
• Overall Status: Completed
• CT.gov ID: NCT00667563
• Collaborator: National Cancer Institute (NCI) (NIH), The Emmes Company, LLC (Industry)
• Enrollment: 150
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 3.8

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines made from virus proteins may help the body build an effective immune response to prevent cervical cancer.

PURPOSE: This pilot study is looking at the side effects of a human papillomavirus vaccine and how well it works in preventing cervical cancer in women in India with HIV-1 infection.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer; Nonneoplastic Condition; Precancerous Condition	Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine; Genetic: DNA analysis; Genetic: polymerase chain reaction; Other: cytology specimen collection procedure; Procedure: colposcopic biopsy	Phase 1

Detailed Description

OBJECTIVES:

Primary

• Assess the safety of the Gardasil® quadrivalent human papillomavirus (HPV) (types 6, 11, 16,18) virus-like-particle vaccine with vs without prior exposure to one or more of the HPV types in the vaccine in HIV-positive women in Chennai, India.

• Determine the effect of the vaccine on HIV viral load and CD4+/CD8+ levels in these patients.

• Determine the proportion of these patients who respond serologically to the HPV vaccine and the kinetics of their response.

Secondary

• Determine the prevalence and incidence of cervical intraepithelial neoplasia in these patients.

• Determine the spectrum of cervical HPV types in these patients at baseline, 9 months, and 1 year after vaccination.

OUTLINE: This is a multicenter study.

Patients receive quadrivalent human papillomavirus (HPV) (types 6, 11, 16, 18) recombinant vaccine intramuscularly on day 0 and once in weeks 8 and 24.

Patients undergo cervical cell, buccal cell, and blood sample collection at baseline and periodically after vaccination for immunologic and virologic studies. Cervical cytology specimens are examined by polymerase chain reaction to detect HPV 6, 11, 16, or 18 DNA, as well as 35 other HPV types. Blood samples are analyzed for CD4+/CD8+ cell count, plasma HIV-1 RNA levels, and serum HPV antibody titers for HPV types 6, 11, 16, and 18. Some plasma samples will be stored for future HPV pseudovirion neutralization assays.

After completion of study therapy, patients are followed periodically for up to 12 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Single-Arm, Open-Label Pilot Study of the Safety and Immunogenicity of the Merck Quadrivalent Human Papillomavirus Vaccine Among HIV-Positive Women in India
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Gardasil Vaccination Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.

Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine; Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.; Genetic: DNA analysis; Weeks 0, 2, 10, 26, and 52.; Other Names: HIV viral load test and HPV neutralization assays. ; Genetic: polymerase chain reaction; Screening, week 36, and week 52.; Other: cytology specimen collection procedure; Screening, week 36, and week 52.; Procedure: colposcopic biopsy; Screening, week 36, and week 52.

Outcome Measures

Primary Outcome Measures

1. Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0 [52 weeks from study entry]

   Number of grade 3 or 4 adverse events attributed to vaccine per 100 patients

2. Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count [Screening/Week 0, Weeks 2, 10, 26, and 52.]

   Significant decrease (at the 0.05 significance level) in CD4+ cell count to 75% of the baseline level on two or more consecutive tests

3. Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28 [Week 28]

   Number of participants with detectable HPV antibody to HPV 16 among those with undetectable antibodies to HPV 16 at baseline

4. Number of Patients With a Significant Increase in HIV Viral Load [Screening/week 0, weeks, 2, 10, 26 and 52]

   Number of patients with a significant increase in HIV viral load defined as > 1 log increase in HIV load from baseline on 2 consecutive occasions

5. Number of Patients With Detectable Antibodies to HPV-6 [28 weeks]

   Detectable antibodies to HPV-6 among participant who had undetectable antibodies to HPV-6 at baseline

6. Number of Patients With Detectable Antibodies to HPV-11 [28 weeks]

   Detectable antibodies to HPV-11 among those who had undetectable antibodies to HPV-11 at baseline

7. Number of Patients With Detectable Antibodies to HPV-18 [28 weeks]

   Detectable antibodies to HPV-18 among participants with undetectable antibodies to HPV-18 at baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by western blot before study entry

• HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test

• Meets 1 of the following criteria:

• Nadir CD4 level of ≤ 350 cells/mm³ and receiving highly active antiretroviral therapy (HAART) for at least 6 months before study entry

• Nadir CD4 level of > 350 cells/mm³ and not receiving HAART at the time of study entry

• No known history of high-grade CIN or cervical cancer

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%

• ANC > 750 cells/mm³

• Hemoglobin ≥ 9.0 g/dL

• Platelet count ≥ 100,000/mm³

• Serum creatinine ≤ 3 times upper limit of normal (ULN)

• AST and ALT ≤ 3.0 times ULN

• Conjugated (direct) bilirubin ≤ 2.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No active drug or alcohol use or dependence that would interfere with adherence to study requirements, in the opinion of the site Investigator

• No serious illness requiring systemic treatment and/or hospitalization within the past 45 days

• No allergy to yeast or any of the components of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 45 days since prior systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin

• Routine standard of care, including hepatitis B, influenza, and tetanus vaccines are allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	YRG Care	Chennai		India	600113

Sponsors and Collaborators

• AIDS Malignancy Consortium
• National Cancer Institute (NCI)
• The Emmes Company, LLC

Investigators

• Study Chair: Joel Palefsky, MD, University of California, San Francisco
• Principal Investigator: N. Kumarasamy, MD, YRG Care

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AIDS Malignancy Consortium
• ClinicalTrials.gov Identifier: NCT00667563
• Other Study ID Numbers: AMC-054; U01CA121947; CDR0000593634
• First Posted: Apr 28, 2008
• Last Update Posted: Feb 29, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by AIDS Malignancy Consortium: human papilloma virus infection; cervical cancer; cervical intraepithelial neoplasia; HIV infection
• Additional relevant MeSH terms: Uterine Cervical Neoplasms; Precancerous Conditions; Disease

Study Results

Participant Flow

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
Period Title: Overall Study
STARTED	150
COMPLETED	126
NOT COMPLETED	24

Baseline Characteristics

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
Overall Participants	150
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.8 (5.2)
Sex: Female, Male (Count of Participants)
Female	150 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0
Description	Number of grade 3 or 4 adverse events attributed to vaccine per 100 patients
Time Frame	52 weeks from study entry

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
Measure Participants	150
Number (95% Confidence Interval) [Grade 3/4 adverse events per 100 patient]	6.0

2. Primary Outcome

Title	Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count
Description	Significant decrease (at the 0.05 significance level) in CD4+ cell count to 75% of the baseline level on two or more consecutive tests
Time Frame	Screening/Week 0, Weeks 2, 10, 26, and 52.

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
Measure Participants	150
Number [participants]	11 7.3%

3. Primary Outcome

Title	Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28
Description	Number of participants with detectable HPV antibody to HPV 16 among those with undetectable antibodies to HPV 16 at baseline
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per-protocol population with undetectable HPV-16 levels at baseline

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
Measure Participants	96
Number [participants]	95 63.3%

4. Primary Outcome

Title	Number of Patients With a Significant Increase in HIV Viral Load
Description	Number of patients with a significant increase in HIV viral load defined as > 1 log increase in HIV load from baseline on 2 consecutive occasions
Time Frame	Screening/week 0, weeks, 2, 10, 26 and 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
Measure Participants	150
Number [participants]	7 4.7%

5. Primary Outcome

Title	Number of Patients With Detectable Antibodies to HPV-6
Description	Detectable antibodies to HPV-6 among participant who had undetectable antibodies to HPV-6 at baseline
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

Per-protocol participants with undetectable antibodies to HPV-6 at baseline

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
Measure Participants	88
Number [participants]	88 58.7%

6. Primary Outcome

Title	Number of Patients With Detectable Antibodies to HPV-11
Description	Detectable antibodies to HPV-11 among those who had undetectable antibodies to HPV-11 at baseline
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

Per-protocol population of participants with undetectable antibodies for HPV-11 at baseline

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
Measure Participants	111
Number [participants]	110 73.3%

7. Primary Outcome

Title	Number of Patients With Detectable Antibodies to HPV-18
Description	Detectable antibodies to HPV-18 among participants with undetectable antibodies to HPV-18 at baseline
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

Per-protocol population of participants with undetectable HPV-18 antibodies at baseline

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
Measure Participants	104
Number [participants]	94 62.7%

Adverse Events

Arm/Group Title	Gardasil Vaccination
Arm/Group Description	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. DNA analysis: Weeks 0, 2, 10, 26, and 52. polymerase chain reaction: Screening, week 36, and week 52. cytology specimen collection procedure: Screening, week 36, and week 52. colposcopic biopsy: Screening, week 36, and week 52.
All Cause Mortality
	Gardasil Vaccination
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gardasil Vaccination
	Affected / at Risk (%)	# Events
Total	4/150 (2.7%)
Blood and lymphatic system disorders
Anemia	1/150 (0.7%)	1
General disorders
Fever	1/150 (0.7%)	1
Infections and infestations
Meningitis	1/150 (0.7%)	1
Lung Infection	1/150 (0.7%)	1
Leptospirosis	1/150 (0.7%)	1
Nervous system disorders
Seizure	1/150 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Gardasil Vaccination
	Affected / at Risk (%)	# Events
Total	145/150 (96.7%)
Gastrointestinal disorders
Abdominal pain	35/150 (23.3%)	41
Dyspepsia	19/150 (12.7%)	22
Vomiting	10/150 (6.7%)	11
General disorders
Fatigue	27/150 (18%)	32
Infections and infestations
Lung Infection	8/150 (5.3%)	8
Skin Infection	26/150 (17.3%)	29
Upper Respiratory Infection	44/150 (29.3%)	60
Vaginal Infection	21/150 (14%)	22
Vulval Infection	10/150 (6.7%)	10
Metabolism and nutrition disorders
Anorexia	21/150 (14%)	24
Musculoskeletal and connective tissue disorders
Arthralgia	9/150 (6%)	11
Back pain	27/150 (18%)	40
Myalgia	25/150 (16.7%)	34
Pain in extremity	45/150 (30%)	61
Nervous system disorders
Headache	34/150 (22.7%)	47
Reproductive system and breast disorders
Vaginal Discharge	21/150 (14%)	27
Cough	59/150 (39.3%)	87
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	18/150 (12%)	22
Skin and subcutaneous tissue disorders
Pruritus	41/150 (27.3%)	64
Rash, maculo-papular	14/150 (9.3%)	16

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.