Safety of and Immune Response to a Novel Human Papillomavirus Vaccine in HIV Infected Children

This study has been completed.

Sponsor:

Collaborator:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT00339040

First received: June 19, 2006

Last updated: March 1, 2013

Last verified: March 2013

History of Changes

Results First Received: September 7, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Prevention
Conditions:	HIV Infections Sexually Transmitted Diseases
Interventions:	Biological: Quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV) Other: Placebo/QHPV

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Between October 11, 2006 and November 22, 2006 130 participants were enrolled at 34 clinical sites from US & Puerto Rico.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were stratified by CD4% criteria. Four participants were randomized but did not receive the study treatment. The study analyses were based on 126 participants who received the study treatment.

Reporting Groups

	Description
Arm A QHPV	Participants received three doses of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 0, 8, and 24 and an additional dose at week 96.
Arm B Placebo/QHPV	Participants received three doses of the placebo at week 0, 8, and 24 and additional dose of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 96, 104 and 120.

Participant Flow for 2 periods

Period 1: Stage I

	Arm A QHPV	Arm B Placebo/QHPV
STARTED	96	30
Vaccination 1 at Week 0	96	30
Vaccination 2 at Week 8	95	30
Vaccination 3 at Week 24	94	30
COMPLETED	94	29
NOT COMPLETED	2	1
Not able to attend clinic	1	0
Protocol Violation	1	1

Period 2: Stage II

	Arm A QHPV	Arm B Placebo/QHPV
STARTED	94	29
Vaccination 4 at Week 96	84	29
Vaccination 5 at Week 104	0	28
Vaccination 6 at Week 120	0	27
COMPLETED	84	27
NOT COMPLETED	10	2
Lost to Follow-up	3	0
Withdrawal by Subject	1	2
Protocol Violation	3	0
Not able to attend clinic	1	0
Site closing	2	0

Baseline Characteristics

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Reporting Groups

	Description
Arm A QHPV	Participants received three doses of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 0, 8, and 24 and an additional dose at week 96.
Arm B Placebo/QHPV	Participants received three doses of the placebo at week 0, 8, and 24 and additional dose of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 96, 104 and 120.
Total	Total of all reporting groups

Baseline Measures

	Arm A QHPV	Arm B Placebo/QHPV	Total
Number of Participants [units: participants]	96	30	126
Age [units: years] Mean ± Standard Deviation	10.0 ± 1.4	9.9 ± 1.3	9.9 ± 1.4
Gender [units: participants]
Female	53	18	71
Male	43	12	55
Race/Ethnicity, Customized [units: participants]
White, non-Hispanic	4	2	6
Black, non-Hispanic	54	11	65
Hispanic	37	14	51
Others	1	3	4
Stratification groups ^[1] [units: participants]
Stratum A	31	10	41
Stratum B	32	11	43
Stratum C	33	9	42
CD4 count [units: cells/µL] Mean ± Standard Deviation	868 ± 367	1013 ± 455	903 ± 393
CD4% [units: percentage of total lymphocytes] Mean ± Standard Deviation	33.9 ± 7.9	35.8 ± 8.6	34.3 ± 8.1
Log10(RNA) [units: Log10(copies/mL)] Mean ± Standard Deviation	2.7 ± 0.9	2.6 ± 0.8	2.7 ± 0.9
RNA group [units: participants]
≤400 copies/mL	65	22	87
401 to ≤5000 copies/mL	16	5	21
>5000 copies/mL	15	3	18

[1]	STRATIFICATION: Participant were stratified by CD4% criteria into three strata: Stratum A: CD4% Nadir < 15 and CD4% ≥ 15 at screening Stratum B: CD4% Nadir ≥ 15 and < 25 and CD4% ≥ 15 at screening Stratum C: CD4% Nadir ≥ 25 and CD4% ≥ 25 at screening

Outcome Measures

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1. Primary:

Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) [ Time Frame: Within 14 days of first three doses of vaccination ]

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Measure Type	Primary
Measure Title	Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs)
Measure Description	Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (December 2004). The grades used are: Grade 1="Mild", Grade 2="Moderate", Grade 3="Severe", Grade 4="Potentially Life-Threatening". All grade 3 and higher signs, symptoms, and laboratory toxicities were included.
Time Frame	Within 14 days of first three doses of vaccination
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Any participant who received at least one study vaccine/placebo were included in the safety analysis.

Reporting Groups

	Description
Arm A QHPV	Participants received three doses of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 0, 8, and 24 and an additional dose at week 96.
Arm B Placebo/QHPV	Participants received three doses of the placebo at week 0, 8, and 24 and additional dose of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 96, 104 and 120.

Measured Values

	Arm A QHPV	Arm B Placebo/QHPV
Number of Participants Analyzed [units: participants]	96	30
Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) [units: percent of participants] Number ( 95% Confidence Interval )	7.3 ( 3.0 to 14.5 )	6.7 ( 0.8 to 22.1 )

Statistical Analysis 1 for Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs)

Groups ^[1]	All groups
Method ^[2]	Fisher Exact
P Value ^[3]	1.00

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
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[2]	Other relevant information, such as adjustments or degrees of freedom:
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[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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2. Primary:

Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) Attributed to Study Treatment [ Time Frame: Within 14 days of first three doses of vaccination ]

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3. Primary:

Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion [ Time Frame: At week 28 after beginning the vaccination series ]

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4. Primary:

Serum Anti-HPV Antibody Titers (cLIA) [ Time Frame: Arm A week 0, 28, 72, 96, 97, 100; Arm B week 0, 28, 72, 96, 97, 100, 124. ]

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5. Secondary:

CD4 Count Over Time [ Time Frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. ]

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6. Secondary:

CD4 Percent Over Time [ Time Frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. ]

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7. Secondary:

HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time [ Time Frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS 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.

The agreement is:

	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.
	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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and Merck & Co., Inc., NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617) 432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu

Publications of Results:

Levin MJ, Moscicki AB, Song LY, Fenton T, Meyer WA 3rd, Read JS, Handelsman EL, Nowak B, Sattler CA, Saah A, Radley DR, Esser MT, Weinberg A; for the IMPAACT P1047 Protocol Team. Safety and Immunogenicity of a Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) Vaccine in HIV-Infected Children 7 to 12 Years Old. J Acquir Immune Defic Syndr. 2010 Jun 22; [Epub ahead of print]

Other Publications:

Ault KA, Giuliano AR, Edwards RP, Tamms G, Kim LL, Smith JF, Jansen KU, Allende M, Taddeo FJ, Skulsky D, Barr E. A phase I study to evaluate a human papillomavirus (HPV) type 18 L1 VLP vaccine. Vaccine. 2004 Aug 13;22(23-24):3004-7.

Brown DR, Fife KH, Wheeler CM, Koutsky LA, Lupinacci LM, Railkar R, Suhr G, Barr E, Dicello A, Li W, Smith JF, Tadesse A, Jansen KU. Early assessment of the efficacy of a human papillomavirus type 16 L1 virus-like particle vaccine. Vaccine. 2004 Jul 29;22(21-22):2936-42.

Poland GA, Jacobson RM, Koutsky LA, Tamms GM, Railkar R, Smith JF, Bryan JT, Cavanaugh PF Jr, Jansen KU, Barr E. Immunogenicity and reactogenicity of a novel vaccine for human papillomavirus 16: a 2-year randomized controlled clinical trial. Mayo Clin Proc. 2005 May;80(5):601-10.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00339040 History of Changes
Other Study ID Numbers:	P1047, 10163, PACTG P1047
Study First Received:	June 19, 2006
Results First Received:	September 7, 2011
Last Updated:	March 1, 2013
Health Authority:	United States: Food and Drug Administration

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