Trial Outcomes & Findings for A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents, and Young Adults (NCT NCT00798265)

Last Updated: 2024-11-20

Results Overview

Immunogenicity was measured by the vaccine-induced antibody response collectively for preadolescents, adolescents and young adults an reported per cohort for participants with HIV and without HIV. Participants' serum was used to check the level of human papillomavirus (HPV) neutralization antibody. Neutralizing antibody is an antibody that can bind to the infectious organism such as viruses and stop the spread of the disease. The antibody level was compared between the participants with HIV and without HIV.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

26 participants

Primary outcome timeframe

Up to 36 months

Results posted on

2024-11-20

Participant Flow

No participants were enrolled in Cohort 2 - 0.5 mL dose injected intramuscular (IM) group.

Participant milestones

Participant milestones
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Overall Study STARTED	8	18
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	8	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Overall Study Lost to Follow-up	1	10
Overall Study Study closing	7	6
Overall Study Withdrawal by Subject	0	1
Overall Study Screen failure	0	1

Baseline Characteristics

A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents, and Young Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 - 0.5 mL Dose Injected Intramuscular (IM) n=8 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 - 0.5 mL Dose Injected Intramuscular (IM) n=18 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls	Total n=26 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	18.68 years STANDARD_DEVIATION 3.9 • n=5 Participants	20.86 years STANDARD_DEVIATION 5.1 • n=7 Participants	20.19 years STANDARD_DEVIATION 4.8 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	16 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	12 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	18 participants n=7 Participants	26 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 36 months

Population: No participants were analyzed at 48 months because they were all of study before month 48 and the study ended.

Outcome measures

Outcome measures
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) n=8 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) n=17 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-16 at Baseline	NA EU/ml Interval 7.0 to 7.0 Geometric mean is below the detectable limit (\<7).	12.24 EU/ml Interval 7.0 to 29.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-18 at 7 Months	1453.32 EU/ml Interval 424.6 to 9273.0	1171.10 EU/ml Interval 201.0 to 9659.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-18 at 12 Months	409.57 EU/ml Interval 71.67 to 3745.0	478.98 EU/ml Interval 77.0 to 8920.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-6 at Baseline	NA EU/ml Interval 7.0 to 7.0 Geometric mean is below the detectable limit (\<7).	12.24 EU/ml Interval 7.0 to 29.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-6 at 7 Months	955.77 EU/ml Interval 275.2 to 3452.0	598.90 EU/ml Interval 89.0 to 3180.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-6 at 12 Months	311.15 EU/ml Interval 34.4 to 3218.0	286.07 EU/ml Interval 43.0 to 1670.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-6 at 24 Months	280.22 EU/ml Interval 62.19 to 2058.0	186.13 EU/ml Interval 68.0 to 694.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-6 at 36 Months	189.82 EU/ml Interval 63.14 to 1417.0	169.78 EU/ml Interval 57.0 to 504.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-11 at Baseline	7.00 EU/ml Interval 7.0 to 7.0	14.61 EU/ml Interval 7.0 to 29.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-11 at 7 Months	1873.68 EU/ml Interval 677.6 to 9992.0	1159.81 EU/ml Interval 165.0 to 3937.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-11 at 12 Months	611.98 EU/ml Interval 85.85 to 5620.0	457.23 EU/ml Interval 145.0 to 2195.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-11 at 24 Months	477.21 EU/ml Interval 137.4 to 2806.0	232.88 EU/ml Interval 91.0 to 732.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-11 at 36 Months	285.92 EU/ml Interval 100.8 to 1997.0	171.53 EU/ml Interval 81.0 to 401.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-16 at 7 Months	1943 EU/ml Interval 424.6 to 9273.0	2876 EU/ml Interval 601.13 to 18831.61
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-16 at 12 Months	523.7 EU/ml Interval 71.67 to 3745.0	1155 EU/ml Interval 286.08 to 14845.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-16 at 24 Months	359.7 EU/ml Interval 43.05 to 1462.0	665 EU/ml Interval 148.01 to 6428.56
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-16 at 36 Months	295 EU/ml Interval 47.19 to 1132.0	611 EU/ml Interval 211.49 to 5401.17
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-18 at Baseline	7.00 EU/ml Interval 7.0 to 7.0	8.04 EU/ml Interval 7.0 to 168.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-18 at 24 Months	253.70 EU/ml Interval 43.05 to 1462.0	301.76 EU/ml Interval 101.0 to 2856.0
Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age HPV-18 at 36 Months	202.29 EU/ml Interval 47.19 to 1132.0	289.66 EU/ml Interval 97.0 to 1756.0

SECONDARY outcome

Timeframe: At study entry

Population: This outcome measure was not done because no participants were enrolled in Cohort 2 - 0.5 mL dose injected intramuscular (IM) group.

Match per the HIV level at study entry to compare between cohort 1 and 2.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, and months 1, 3, 7 and 12

Population: Only Cohort 1 is applicable for this outcome measure.

Within each cohort, the number of participants with a change in log\^10 HIV-1 RNA levels will be determined between day 1 and day 7 and will be evaluated to see if the values at the two time points are not statistically different from one another. HIV-1 RNA levels below the lower limits of detection (50 copies/ml) will be expressed as 1.69 log\^10 on a logarithmic scale equivalent to 49 copies/ml. There is at least 95% power to detect a change from day 1 to day 7 with an effect size of 1 standard deviation (SD) and a 0.025 two-sided alpha level test (0.05/2 cohorts) after allowing for a Bonferroni adjustment.

Outcome measures

Outcome measures
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) n=8 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Number of Participants With Log Change in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels After Human Papilloma Virus (HPV) Vaccination 3 Months	NA Participants HIV RNA was undetectable or lower than baseline.	—
Number of Participants With Log Change in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels After Human Papilloma Virus (HPV) Vaccination Baseline	1 Participants	—
Number of Participants With Log Change in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels After Human Papilloma Virus (HPV) Vaccination 1 Month	NA Participants HIV RNA was undetectable or lower than baseline.	—
Number of Participants With Log Change in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels After Human Papilloma Virus (HPV) Vaccination 7 Months	1 Participants	—
Number of Participants With Log Change in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels After Human Papilloma Virus (HPV) Vaccination 12 Months	NA Participants HIV RNA was undetectable or lower than baseline.	—

SECONDARY outcome

Timeframe: Months 7, 12, 24 and 36

Population: A different number of samples were available for the assay at 7, 12, 24 and 36 months as noted in the table.

Fold change in anti-HPV titer with baseline T-lymphocytes (CD4) count. Fold change is a measure of the antibody titer after vaccination divided by the baseline titer.

Outcome measures

Outcome measures
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) n=8 Blood Samples 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) n=14 Blood Samples 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-6 at 7 months	142.64 Fold Change Interval 39.32 to 493.1	90.22 Fold Change Interval 12.65 to 432.46
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-6 at 36 months	16.70 Fold Change Interval 9.02 to 202.47	24.37 Fold Change Interval 8.13 to 67.37
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-11 at 7 months	235.69 Fold Change Interval 96.79 to 1427.45	189.84 Fold Change Interval 23.57 to 532.02
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-11 at 12 months	68.90 Fold Change Interval 12.26 to 802.92	71.57 Fold Change Interval 6.58 to 296.64
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-6 at 12 months	42.00 Fold Change Interval 4.91 to 459.65	28.48 Fold Change Interval 6.08 to 223.17
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-6 at 24 months	55.00 Fold Change Interval 8.88 to 293.98	18.35 Fold Change Interval 9.05 to 92.65
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-11 at 24 months	69.29 Fold Change Interval 19.63 to 400.79	37.47 Fold Change Interval 4.92 to 98.87
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-11 at 36 months	23.69 Fold Change Interval 14.4 to 285.29	22.22 Fold Change Interval 11.57 to 54.14
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-16 at 7 months	589.91 Fold Change Interval 211.16 to 2978.1	382.60 Fold Change Interval 24.1 to 2690.23
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-16 at 12 months	183.15 Fold Change Interval 59.14 to 805.85	142.79 Fold Change Interval 9.84 to 2120.71
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-16 at 24 months	137.73 Fold Change Interval 40.47 to 437.2	59.87 Fold Change Interval 7.52 to 918.37
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-16 at 36 months	78.30 Fold Change Interval 0.0 to 321.86	30.81 Fold Change Interval 20.34 to 250.89
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-18 at 7 months	145.36 Fold Change Interval 60.66 to 1324.73	142.60 Fold Change Interval 7.66 to 1379.84
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-18 at 12 months	55.35 Fold Change Interval 10.24 to 535.03	39.58 Fold Change Interval 4.64 to 1274.25
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-18 at 24 months	36.63 Fold Change Interval 6.15 to 208.86	22.46 Fold Change Interval 3.28 to 408.05
Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline) anti-HPV-18 at 36 months	94.24 Fold Change Interval 10.0 to 161.72	20.34 Fold Change Interval 13.88 to 250.89

SECONDARY outcome

Timeframe: Baseline

Baseline T-lymphocytes (CD4) count.

Outcome measures

Outcome measures
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) n=8 Blood Samples 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) n=14 Blood Samples 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
T-lymphocytes (CD4) Count (Only at Baseline)	643 Cells/mm^3 Interval 457.0 to 1232.0	753 Cells/mm^3 Interval 425.0 to 2041.0

SECONDARY outcome

Timeframe: Baseline

Population: Data not collected.

Human papillomavirus (HPV) deoxyribonucleic acid (DNA) positivity by oral/buccal swabs was performed by swabbing the oral/buccal mucosa and

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 36 months

HPV DNA positivity by anogenital swabs was performed by Papanicolaou test (PAP) test. PAPs were not conducted when the participant stated that she was not sexually active.

Outcome measures

Outcome measures
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) n=8 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) n=18 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Number of Participants With Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Positivity by Anogenital Swabs	2 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline

Population: Participant data is combined for this outcome measure as pre-specified by the protocol. No statistical comparisons between cohorts were planned.

Here are the number of participants who properly completed (i.e., answered correctly) the YRBSS. The human papilloma virus (HPV) \& human immunodeficiency virus (HIV) knowledge and risk and sexual behaviors was assessed by a middle school or high school version of web-based Youth Risk Behavior Survey developed by Centers for Disease Control and Prevention (CDC). The Youth Risk Behavior Surveillance System (YRBSS) developed by the CDC was used to monitor six categories of priority health risk behaviors among middle school and high school youth: behaviors that contribute to unintentional injuries and violence; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infections; unhealthy dietary behaviors; and physical inactivity and determine the number of participants who answered correctly on the assessment tool (i.e., YRBSS).

Outcome measures

Outcome measures
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) n=26 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Number of Participants Who Completed The Youth Risk Behavior Surveillance System (YRBSS)	26 Participants	—

SECONDARY outcome

Timeframe: 0, 1, 2, 3, 6, 7, 12, 18, 24, 30, 36, 42, and 48 hours

Population: The lab assigned to do this assay was not able to perform the study.

Participants collection Tube: 10ml red top tube (RTT) send via courier to National Cancer Institute (NCI) FCRF for processing, aliquoting and cryopreservation by Baselar lab. Batched specimens to be sent to Merck for HPV antibody titers.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 7 months

Population: 15/18 participants were analyzed in Cohort 3 because one participant was a screen failure, one participant withdrew from study and one participant was taken off study.

Month 7 anti-HPV Ab titer was correlated with Neutralization Assay (PBNA) antibody titers and analyzed by the secreted alkaline phosphatase (SEAP)/enzyme-linked immunosorbent assay (ELISA) R.

Outcome measures

Outcome measures
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) n=8 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) n=15 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Functional Human Papilloma Virus (HPV) Antibody Neutralization Assays HPV-16	0.90476 Coefficient	0.81071 Coefficient
Functional Human Papilloma Virus (HPV) Antibody Neutralization Assays HPV-18	0.97619 Coefficient	0.88571 Coefficient

SECONDARY outcome

Timeframe: 0, 1, 3, 7, 12, 24, 36, and 48 hours

Population: Samples were not available to perform the study. This type of immune assay requires a large number of PBMCs in pairs including baseline samples, but the collection was inadequate for the assay and the assay was not done.

Participants collection tube: 6 tubes sodium heparin 10ml green top tube (GTT) (60ml total) send via courier to National Cancer Institute (NCI) FCRF for processing, aliquoting and cryopreservation by Baselar lab according to protocol provided by the investigator. Note: HIV lymphocyte proliferation assays will only be performed in HIV-infected subjects

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0, 1, 3, 7, 12, 18, 24, 30, 36, 42, and 48 hours

Population: Samples were not available to perform the study. This type of immune assays requires a large number of PBMCs in pairs including baseline samples, but the collection was inadequate for the assay and the assay was not done.

Extended FACS/Quantitative lymphocyte subpopulation studies human immunodeficiency virus (HIV)-infected subjects only (Cohorts 1 and 2) using a 10ml sodium heparin green top tube (GTT).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0, 1, 2, 3, 6, 7, 12, 18, 24, 30, 36, 42, and 48 hours

Population: This outcome measure was not done because there were not enough samples available to do a series (e.g., multiple timepoints).

Collection tube: 10ml red top tube (RTT) send via courier to National Cancer Institute (NCI) FCRF for processing, aliquoting and cryopreservation by Baselar lab.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0, 7, 12, 24, 36, and 48 Months

Population: Data not collected.

Three collection tube: 6ml purple top ethylenediamine tetraacetic acid (EDTA) tubes (18ml total)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 0 only

Population: Data not collected.

Two collection tubes: 10ml sodium heparin green top tube (GTT) (20ml total) from HIV infected subjects only (Cohorts 1 and 2).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, up to 43 months and 8 days

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Cohort 1 -.5 mL Dose Injected Intramuscular (IM) n=8 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 -.5 mL Dose Injected Intramuscular (IM) n=18 Participants 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0)	8 Participants	16 Participants

Adverse Events

Cohort 1 - 0.5 mL Dose Injected Intramuscular (IM)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Cohort 3 - 0.5 mL Dose Injected Intramuscular (IM)

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 - 0.5 mL Dose Injected Intramuscular (IM) n=8 participants at risk 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 - 0.5 mL Dose Injected Intramuscular (IM) n=18 participants at risk 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Infections and infestations Infection with unknown absolute neutrophil count (ANC): Lung (pneumonia)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
General disorders Pain: Abdomen Not Otherwise Specified (NOS)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.

Other adverse events

Additional Information

Dr. Hoyoung Maeng

National Cancer Institute

Phone: 240-781-3253

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1 - 0.5 mL Dose Injected Intramuscular (IM) n=8 participants at risk 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) cell count \> 350 cells/mm\^3, Human immunodeficiency virus type 1 (HIV-1) Ribonucleic acid (RNA) level by reverse transcription-polymerase chain reaction (RT PCR) \<20,000	Cohort 3 - 0.5 mL Dose Injected Intramuscular (IM) n=18 participants at risk 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0 Gardasil: 0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months Survey: Administration of online risk behavior and knowledge survey done at week 0. Healthy, Human immunodeficiency virus (HIV)-negative controls
Metabolism and nutrition disorders ALT, SGPT (serum glutamic pyruvic transaminase)	87.5% 7/8 • Number of events 11 • Date treatment consent signed to date off study, up to 43 months and 8 days.	16.7% 3/18 • Number of events 4 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders AST, SGOT(serum glutamic oxaloacetic transaminase)	37.5% 3/8 • Number of events 5 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	62.5% 5/8 • Number of events 7 • Date treatment consent signed to date off study, up to 43 months and 8 days.	22.2% 4/18 • Number of events 4 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Alkaline phosphatase	62.5% 5/8 • Number of events 5 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Immune system disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Bicarbonate, serum-low	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	12.5% 1/8 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.	11.1% 2/18 • Number of events 7 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders CPK (creatine phosphokinase)	50.0% 4/8 • Number of events 7 • Date treatment consent signed to date off study, up to 43 months and 8 days.	22.2% 4/18 • Number of events 7 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Calcium, serum-high (hypercalcemia)	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	11.1% 2/18 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Gastrointestinal disorders Colitis	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Colitis, infectious (e.g., Clostridium difficile)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 2/8 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Creatinine	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	11.1% 2/18 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Renal and urinary disorders Cystitis	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (Lesion)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (Macular eruption)	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (Papulopustular eruption)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (Wart)	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Gastrointestinal disorders Diarrhea	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	11.1% 2/18 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Nervous system disorders Dizziness	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
General disorders Fatigue (asthenia, lethargy, malaise)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	16.7% 3/18 • Number of events 4 • Date treatment consent signed to date off study, up to 43 months and 8 days.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
General disorders Flu-like syndrome	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Blood and lymphatic system disorders Hemoglobin	37.5% 3/8 • Number of events 4 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Gastrointestinal disorders Hemorrhage, GI::Rectum	12.5% 1/8 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Reproductive system and breast disorders Hemorrhage, GU::Vagina	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Respiratory, thoracic and mediastinal disorders Hemorrhage, pulmonary/upper respiratory::Nose	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection - Other (Flu)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection - Other (H1N1 influenza)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection - Other (Herpes)	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection - Other (Upper airway NOS)	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection - Other (Upper airway strep infection)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils::Lip/perioral	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils::Middle ear (otitis media)	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils::Pharynx	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils::Soft tissue NOS	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils::Vagina	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with unknown ANC::Middle ear (otitis media)	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with unknown ANC::Skin (cellulites)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with unknown ANC::Upper airway NOS	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with unknown ANC::Urinary tract NOS	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Infections and infestations Infection with unknown ANC::Vagina	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Skin and subcutaneous tissue disorders Injection site reaction/extravasation changes	62.5% 5/8 • Number of events 13 • Date treatment consent signed to date off study, up to 43 months and 8 days.	55.6% 10/18 • Number of events 22 • Date treatment consent signed to date off study, up to 43 months and 8 days.
General disorders Insomnia	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Blood and lymphatic system disorders Leukocytes (total WBC)	25.0% 2/8 • Number of events 4 • Date treatment consent signed to date off study, up to 43 months and 8 days.	22.2% 4/18 • Number of events 6 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Blood and lymphatic system disorders Lymphopenia	12.5% 1/8 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.	22.2% 4/18 • Number of events 6 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Magnesium, serum-high (hypermagnesemia)	37.5% 3/8 • Number of events 5 • Date treatment consent signed to date off study, up to 43 months and 8 days.	27.8% 5/18 • Number of events 6 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	37.5% 3/8 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.	22.2% 4/18 • Number of events 4 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Gastrointestinal disorders Mucositis/stomatitis (functional/symptomatic)::Oral cavity	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	12.5% 1/8 • Number of events 6 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Eye disorders Ocular/Visual - Other (Linear visual field deficit OS)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Gastrointestinal disorders Pain::Abdomen NOS	25.0% 2/8 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.	16.7% 3/18 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Musculoskeletal and connective tissue disorders Pain::Extremity-limb	25.0% 2/8 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	12.5% 1/8 • Number of events 4 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Blood and lymphatic system disorders Platelets	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	11.1% 2/18 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Skin and subcutaneous tissue disorders Pruritus/itching	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Skin and subcutaneous tissue disorders Rash/desquamation	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	27.8% 5/18 • Number of events 7 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Sodium, serum-high (hypernatremia)	37.5% 3/8 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.	11.1% 2/18 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Cardiac disorders Supraventricular and nodal arrhythmia::Sinus tachycardia	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	11.1% 2/18 • Number of events 2 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Cardiac disorders Supraventricular and nodal arrhythmia::Supraventricular tachycardia	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Metabolism and nutrition disorders Uric acid, serum-high (hyperuricemia)	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Reproductive system and breast disorders Vaginal discharge (non-infectious)	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
Gastrointestinal disorders Vomiting	0.00% 0/8 • Date treatment consent signed to date off study, up to 43 months and 8 days.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, up to 43 months and 8 days.
General disorders Weight loss	12.5% 1/8 • Number of events 3 • Date treatment consent signed to date off study, up to 43 months and 8 days.	0.00% 0/18 • Date treatment consent signed to date off study, up to 43 months and 8 days.