GARDASIL: Study to Determine if Gardasil Vaccine is Safe and Effective in Lupus Patients
Study Details
Study Description
Brief Summary
Cervical neoplasia is increased in women with SLE most likely due to cervical infection with human papilloma virus (HPV). 70% of cervical cancer is caused by HPV types 16 and 18. Gardasil vaccine prevents cervical infection with HPV types 16 and 18. Thus lupus patients (who are susceptible to cervical cancer) may benefit from getting Gardasil vaccine which can prevent cervical cancer. Vaccines are generally safe and efficacious in SLE but no studies have been done on the use of this vaccine in SLE. The investigators hypothesize that Gardasil vaccine is safe and effective in SLE. This study will look at vaccine safety in patients with mild to moderate and minimally active or inactive SLE and measure how well they make protective antibodies after receiving the vaccine. In other words this will check how well the vaccine works in SLE.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
To gather safety information and adverse events on the use of Gardasil® in mild to moderate and minimally active or inactive SLE.
To gather information on SLE disease activity flares after vaccination with Gardasil®.
To gather information on the immunogenicity or development of protective anti HPV antibodies SLE after vaccination with Gardasil®.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Gardasil 0.5 ml single dose Gardasil vaccine given at three separate visits |
Drug: Gardasil
0.5 ml Gardasil vaccine in single dose prefilled syringes at Visit 2, Visit 4 and Visit 6
|
Outcome Measures
Primary Outcome Measures
- Frequency of Participants With Adverse Events [1,61,66,181,186,211,330 days]
Frequency of participants with Vaccine site reactions, Frequency of participants with Non Vaccine Adverse Events,
- Number of Non Vaccine Adverse Events [1,61,66,181,186,211,330 days]
the number of non vaccine adverse events
Secondary Outcome Measures
- Seroconversion by HPV Serotypes (HPV 6, HPV 11, HPV 16, HPV 18)as Assessed by Geometric Mean Antibody Titer [Baseline (prevaccine) neutralizing anti HPV antibody titers at visit 1 and anti HPV antibody titers at 1 month post 3rd vaccine shot which is at 7 months in the study.]
1. The percentage of HPV naive women who seroconverted by HPV serotypes was measured using Geometric Mean Titers for HPV serotypes HPV 6, HPV 11, HPV 16, HPV 18
- SLE Disease Activity Flares [1,61,66,181,186,211,330 days]
SELENA-SLEDAI measurements > or = to 2 The SELENA/SLEDAI is a validated instrument which is used to score disease activity and define flares with the SELENA-SLEDAI score range being 0-105, with 0 indicating inactive disease.The SELENA/SLEDAI instrument consists of 24 items, each with a definition of activity; there are 16 clinical items and 8 laboratory items. Although there are no set standards, inactive or minimal disease is generally reflected by a SELENA/SLEDAI score of less than or equal to 2 while more than minimally active disease is reflected by a score of >2.
Eligibility Criteria
Criteria
Inclusion Criteria:
Diagnosis of systemic lupus erythematosis (SLE) by the American College of Rheumatology (ACR) Criteria.
History of a positive antinuclear antibody (ANA) test result at any time in the past.
40 participants with history of mild to moderate SLE disease Minimally active or inactive SLE disease, i.e., (Safety of Estrogens in Lupus Erythematosis National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), SELENA-SLEDAI ≤2 at the start of the study.
Age ≥ 18 years and ≤ 50 years. Gender: females Ability to provide informed consent. Maintenance Prednisone dose ≤ 15 mg/day. Plaquenil ≤ 400 mg/day.
Exclusion Criteria:
Hypersensitivity to any vaccine component Active infections including but not limited to human immunodeficiency virus (HIV positive), Hepatitis B or C, tuberculosis.
Positive purified protein derivative (PPD) test results without evidence of prior treatment or administration of bacilli Calmette-Guerin (BCG) vaccine. A positive PPD is defined as ≥ 5 mm induration 24-38 hours after receiving 5TU (TU=tuberculin units) of PPD.
Pregnancy or desire to become pregnant during the study period. Breast feeding. Inability to complete the immunization series. Received any blood product or component in the previous 6 months before enrollment.
Received any inactivated vaccine product within 14 days before enrollment. Received any live vaccine product within 21 days before enrollment.
Fever (temperature > 100°F) at the time of enrollment. Inability to provided informed consent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | DCaTS-Clinical Research Center | Detroit | Michigan | United States | 48201 |
Sponsors and Collaborators
- Wayne State University
- Merck Sharp & Dohme LLC
Investigators
- Principal Investigator: Patricia J Dhar, MD, Wayne State University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 0412GARDASIL
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Gardasil |
|---|---|
| Arm/Group Description | Single treatment arm: 0.5 ml single dose Gardasil vaccine given at three separate visits Gardasil: 0.5 ml Gardasil vaccine in single dose prefilled syringes at Visit 2, Visit 4 and Visit 6 Total of 7 study visits with vaccines given at visits 2,4 and 6 |
| Period Title: Overall Study | |
| STARTED | 37 |
| COMPLETED | 34 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | Gardasil |
|---|---|
| Arm/Group Description | Single treatment arm: 0.5 ml single dose Gardasil vaccine given at three separate visits Gardasil: 0.5 ml Gardasil vaccine in single dose prefilled syringes at Visit 2, Visit 4 and Visit 6 Total of 7 study visits with vaccines given at visits 2,4 and 6 |
| Overall Participants | 34 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
38.1
(7.9)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
34
100%
|
| Male |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
27
79.4%
|
| White |
6
17.6%
|
| More than one race |
1
2.9%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
34
100%
|
Outcome Measures
| Title | Frequency of Participants With Adverse Events |
|---|---|
| Description | Frequency of participants with Vaccine site reactions, Frequency of participants with Non Vaccine Adverse Events, |
| Time Frame | 1,61,66,181,186,211,330 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Gardasil |
|---|---|
| Arm/Group Description | Single treatment arm: 0.5 ml single dose Gardasil vaccine given at three separate visits Gardasil: 0.5 ml Gardasil vaccine in single dose prefilled syringes at Visit 2, Visit 4 and Visit 6 Total of 7 study visits with vaccines given at visits 2,4 and 6 |
| Measure Participants | 34 |
| vaccine site reactions |
21
61.8%
|
| non vaccine site reactions |
33
97.1%
|
| Title | Number of Non Vaccine Adverse Events |
|---|---|
| Description | the number of non vaccine adverse events |
| Time Frame | 1,61,66,181,186,211,330 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of non vaccine adverse events |
| Arm/Group Title | Gardasil |
|---|---|
| Arm/Group Description | Single treatment arm: 0.5 ml single dose Gardasil vaccine given at three separate visits Gardasil: 0.5 ml Gardasil vaccine in single dose prefilled syringes at Visit 2, Visit 4 and Visit 6 Total of 7 study visits with vaccines given at visits 2,4 and 6 |
| Measure Participants | 34 |
| non vaccine adverse events |
493
|
| serious adverse events |
9
|
| Title | Seroconversion by HPV Serotypes (HPV 6, HPV 11, HPV 16, HPV 18)as Assessed by Geometric Mean Antibody Titer |
|---|---|
| Description | 1. The percentage of HPV naive women who seroconverted by HPV serotypes was measured using Geometric Mean Titers for HPV serotypes HPV 6, HPV 11, HPV 16, HPV 18 |
| Time Frame | Baseline (prevaccine) neutralizing anti HPV antibody titers at visit 1 and anti HPV antibody titers at 1 month post 3rd vaccine shot which is at 7 months in the study. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The percentage of Human Papilloma Virus (HPV) naive women for HPV serotypes 6, 11, 16 and 18 that seroconverted |
| Arm/Group Title | HPV Serotype Naive Women |
|---|---|
| Arm/Group Description | Single treatment arm: 0.5 ml single dose Gardasil vaccine given at three separate visits Gardasil: 0.5 ml Gardasil vaccine in single dose prefilled syringes at Visit 2, Visit 4 and Visit 6 Total of 7 study visits with vaccines given at visits 2,4 and 6 |
| Measure Participants | 34 |
| HPV 6 Serotype |
100
|
| HPV 11 Serotype |
100
|
| HPV 16 Serotype |
100
|
| HPV 18 Serotype |
100
|
| Title | SLE Disease Activity Flares |
|---|---|
| Description | SELENA-SLEDAI measurements > or = to 2 The SELENA/SLEDAI is a validated instrument which is used to score disease activity and define flares with the SELENA-SLEDAI score range being 0-105, with 0 indicating inactive disease.The SELENA/SLEDAI instrument consists of 24 items, each with a definition of activity; there are 16 clinical items and 8 laboratory items. Although there are no set standards, inactive or minimal disease is generally reflected by a SELENA/SLEDAI score of less than or equal to 2 while more than minimally active disease is reflected by a score of >2. |
| Time Frame | 1,61,66,181,186,211,330 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of patients who had a lupus flare defined by a SELENA -SLEDAI > or = to 2 |
| Arm/Group Title | Gardasil |
|---|---|
| Arm/Group Description | Single treatment arm: 0.5 ml single dose Gardasil vaccine given at three separate visits Gardasil: 0.5 ml Gardasil vaccine in single dose prefilled syringes at Visit 2, Visit 4 and Visit 6 Total of 7 study visits with vaccines given at visits 2,4 and 6 |
| Measure Participants | 34 |
| Count of Participants [Participants] |
0
0%
|
Adverse Events
| Time Frame | Data was collected for 18 months for each patient over the trial study period | |
|---|---|---|
| Adverse Event Reporting Description | Adverse events (AEs) were collected by: 30 minute post vaccine unsolicited AEs--via 30 minute post vaccine AE recording sheet 7 day post vaccine solicited AEs-- via 7 day memory aide recording sheet and reminder phone call 72 to 96 hours after each vaccination 30 day post vaccine unsolicited AEs-- via 30 day diary and weekly phone calls. weekly phone calls once per month scripted phone calls | |
| Arm/Group Title | Gardasil | |
| Arm/Group Description | Single treatment arm: 0.5 ml single dose Gardasil vaccine given at three separate visits Gardasil: 0.5 ml Gardasil vaccine in single dose prefilled syringes at Visit 2, Visit 4 and Visit 6 Total of 7 study visits with vaccines given at visits 2,4 and 6 | |
All Cause Mortality |
||
| Gardasil | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/34 (0%) | |
Serious Adverse Events |
||
| Gardasil | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/34 (2.9%) | |
| Gastrointestinal disorders | ||
| nausea and vomiting with hypertensive crisis | 1/34 (2.9%) | 1 |
| Immune system disorders | ||
| shortness of breath and itching after eating peanut butter | 1/34 (2.9%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Chest pain and arm pain | 1/34 (2.9%) | 1 |
| Chest pain and shortness of breath with left sided numbness | 1/34 (2.9%) | 1 |
| chest pain non cardiogenic | 1/34 (2.9%) | 1 |
| swollen left leg with ulcer | 1/34 (2.9%) | 1 |
| Pregnancy, puerperium and perinatal conditions | ||
| unplanned pregnancy | 1/34 (2.9%) | 1 |
| unplanned pregnancy | 1/34 (2.9%) | 1 |
| Reproductive system and breast disorders | ||
| pain, swelling and discharge of the right breast | 1/34 (2.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Gardasil | ||
| Affected / at Risk (%) | # Events | |
| Total | 33/34 (97.1%) | |
| Blood and lymphatic system disorders | ||
| Blood and Lymphatic system disorders | 3/34 (8.8%) | 3 |
| Cardiac disorders | ||
| Cardiac disorders | 2/34 (5.9%) | 2 |
| Ear and labyrinth disorders | ||
| Ear and labyrinth disorders | 3/34 (8.8%) | 4 |
| Eye disorders | ||
| Eye disorders | 3/34 (8.8%) | 3 |
| Gastrointestinal disorders | ||
| Gastrointestinal disorders | 18/34 (52.9%) | 49 |
| General disorders | ||
| General disorders | 17/34 (50%) | 45 |
| Hepatobiliary disorders | ||
| Hepatobiliary disorders-other | 1/34 (2.9%) | 1 |
| Immune system disorders | ||
| immune system disorders | 4/34 (11.8%) | 4 |
| Infections and infestations | ||
| infections | 21/34 (61.8%) | 44 |
| Injury, poisoning and procedural complications | ||
| injury poisoning and procedural complications | 3/34 (8.8%) | 3 |
| Metabolism and nutrition disorders | ||
| Metabolism and nutrition disorders | 7/34 (20.6%) | 8 |
| Musculoskeletal and connective tissue disorders | ||
| musculoskeletal | 24/34 (70.6%) | 106 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| neoplasms benign, malignant and unspecified (incl dysts and polyps) | 2/34 (5.9%) | 2 |
| Nervous system disorders | ||
| nervouus system | 25/34 (73.5%) | 106 |
| Pregnancy, puerperium and perinatal conditions | ||
| Pregnancy , puerperium and perinatal conditions | 2/34 (5.9%) | 2 |
| Psychiatric disorders | ||
| psychiatric disorders | 5/34 (14.7%) | 12 |
| Renal and urinary disorders | ||
| renal and urinary disorders | 6/34 (17.6%) | 6 |
| Reproductive system and breast disorders | ||
| reproductive system and breast disorders | 6/34 (17.6%) | 7 |
| Respiratory, thoracic and mediastinal disorders | ||
| respiratory disorder | 12/34 (35.3%) | 29 |
| Skin and subcutaneous tissue disorders | ||
| dermatologic | 17/34 (50%) | 45 |
| Surgical and medical procedures | ||
| Surgical and medical procedures | 3/34 (8.8%) | 5 |
| Vascular disorders | ||
| vascular disorder | 10/34 (29.4%) | 18 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Dr. J. Patricia Dhar, MD, Principal Investigator |
|---|---|
| Organization | Wayne State University School of Medicine |
| Phone | 313-577-6011 |
| pdhar@med.wayne.edu |
- 0412GARDASIL