Systemic Lupus Erythematosus
Conditions
Keywords
Lupus
Brief summary
The purpose of this study is to evaluate the immunogenicity and safety of the HPV vaccine Gardasil in young women.
Detailed description
Female patients with systemic lupus erythematosus (SLE) have been found have higher rates of persistent HPV infections and precancerous lesions compared to the healthy population. The HPV vaccine Gardasil has been found to be safe and efficacious in females aged 9 to 26 years. There are no data on the immunogenicity and safety of Gardasil in females with SLE. Immune dysfunction related to SLE itself and the immunosuppression secondary to treatment of SLE might prevent patients with SLE from developing an adequate immune response to the vaccine. Also, theoretically, the vaccine might induce a disease exacerbation or production of new autoantibodies. The purpose of this study is to evaluate immunogenicity and safety of Gardasil and its effects on autoantibody profile in female SLE patients aged 9-26 years
Interventions
BIOLOGICALGardasil
0.5 ml Gardasil vaccine will be administered to each patient at months 0,2 and 6.
Sponsors
Merck Sharp & Dohme LLC
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
9 Years to 26 Years
Healthy volunteers
No
Inclusion criteria
* Age: 9 to 26 years of age * Gender: Female * All patients must fulfill the revised American College of Rheumatology Classification Criteria for SLE diagnosis. * Current SLEDAI score ≤ 6 * Written, witnessed informed consent and/or assent will be obtained from the subject and the subject's parents (if under 18 years of age) or legally acceptable representative prior to enrollment
Exclusion criteria
* Acute exacerbation of disease within past 30 days which required increase in corticosteroid dose, initiation of a new immunosuppressive medication, or hospitalization * Current SLEDAI score \> 6 * Patients who have received rituximab in the last 6 months, or are currently on cyclophosphamide treatment * History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine * Previous administration of any HPV vaccine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SLEDAI Change Score | 7 months | Systemic Lupus Erythematosus Disease Activity Index (SLEDAI): change from baseline to 7 months. The SLEDAI scale is a weighted sum of 16 clinical and 8 laboratory items. Scores range from 0 to 105 with higher scores indicating worse outcome. The variable analyzed here is the 7 month score minus the baseline score. Therefore negative values indicate an improvement in outcome. |
| Anti-HPV 16 GMT | 7 months | Geometric mean titre in milli-Merck units per ml (mMu/ml) |
| Anti-HPV 18 Seroconversion | 7 months | % Seropositive |
| Anti-HPV 18 GMT | 7 months | Geometric mean titre in milli-Merck units per ml (mMu/ml) |
| Anti-HPV 6 Seroconversion | 7 months | Percent Seropositive |
| Anti-HPV 6 GMT | 7 months | Geometric mean titre in milli-Merck units per ml (mMu/ml) |
| Anti-HPV 11 Seroconversion | 7 months | % Seropositive |
| Anti-HPV 11 GMT | 7 months | Geometric mean titre in milli-Merck units per ml (mMu/ml) |
| Anti-HPV 16 Seroconversion | 7 months | % Seropositive |
Secondary
| Measure | Time frame |
|---|---|
| Induction or Increase of Autoantibodies (Conversion From Negative Smith to Positive Smith) | 7 months |
| Induction or Increase of Autoantibodies (Conversion From Lupus Anticoagulant Negative to Lupus Anticoagulant Positive) | 7 months |
| Induction or Increase of Autoantibodies (Conversion From Negative Anti-RNP to Positive Anti-RNP) Anti-RNP | 7 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gardasil Vaccine 0.5 ml Gardasil vaccine at months 0, 2, and 6 | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Pregnancy | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Gardasil Vaccine |
|---|---|
| Age, Continuous | 20.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 27 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 27 |
| serious Total, serious adverse events | 2 / 27 |
Outcome results
Primary
Anti-HPV 11 GMT
Geometric mean titre in milli-Merck units per ml (mMu/ml)
Time frame: 7 months
Population: 4 patients did not have month 7 samples available for analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Gardasil Vaccine | Anti-HPV 11 GMT | 596.7 mMu/ml |
Primary
Anti-HPV 11 Seroconversion
% Seropositive
Time frame: 7 months
Population: 4 patients did not have month 7 samples available for analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccine | Anti-HPV 11 Seroconversion | 100 percentage of participants |
Primary
Anti-HPV 16 GMT
Geometric mean titre in milli-Merck units per ml (mMu/ml)
Time frame: 7 months
Population: 4 patients did not have month 7 samples available for analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Gardasil Vaccine | Anti-HPV 16 GMT | 2263.2 mMu/ml |
Primary
Anti-HPV 16 Seroconversion
% Seropositive
Time frame: 7 months
Population: 4 patients did not have month 7 samples available for analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccine | Anti-HPV 16 Seroconversion | 100 percentage of participants |
Primary
Anti-HPV 18 GMT
Geometric mean titre in milli-Merck units per ml (mMu/ml)
Time frame: 7 months
Population: 4 patients did not have month 7 samples available for analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Gardasil Vaccine | Anti-HPV 18 GMT | 331.9 mMu/ml |
Primary
Anti-HPV 18 Seroconversion
% Seropositive
Time frame: 7 months
Population: 4 patients did not have month 7 samples available for analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccine | Anti-HPV 18 Seroconversion | 93.8 percentage of participants |
Primary
Anti-HPV 6 GMT
Geometric mean titre in milli-Merck units per ml (mMu/ml)
Time frame: 7 months
Population: 4 patients did not have month 7 samples available for analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Gardasil Vaccine | Anti-HPV 6 GMT | 427.0 mMu/ml |
Primary
Anti-HPV 6 Seroconversion
Percent Seropositive
Time frame: 7 months
Population: 4 patients did not have month 7 samples available for analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccine | Anti-HPV 6 Seroconversion | 93.8 percentage of participants |
Primary
SLEDAI Change Score
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI): change from baseline to 7 months. The SLEDAI scale is a weighted sum of 16 clinical and 8 laboratory items. Scores range from 0 to 105 with higher scores indicating worse outcome. The variable analyzed here is the 7 month score minus the baseline score. Therefore negative values indicate an improvement in outcome.
Time frame: 7 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gardasil Vaccine | SLEDAI Change Score | -1.65 units on a scale |
Secondary
Induction or Increase of Autoantibodies (Conversion From Lupus Anticoagulant Negative to Lupus Anticoagulant Positive)
Time frame: 7 months
Population: 17 patients were Lupus anticoagulant negative at entry.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gardasil Vaccine | Induction or Increase of Autoantibodies (Conversion From Lupus Anticoagulant Negative to Lupus Anticoagulant Positive) | 2 Participants |
Secondary
Induction or Increase of Autoantibodies (Conversion From Negative Anti-RNP to Positive Anti-RNP) Anti-RNP
Time frame: 7 months
Population: 8 patients were negative for anti-RNP at entry
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gardasil Vaccine | Induction or Increase of Autoantibodies (Conversion From Negative Anti-RNP to Positive Anti-RNP) Anti-RNP | 0 Participants |
Secondary
Induction or Increase of Autoantibodies (Conversion From Negative Smith to Positive Smith)
Time frame: 7 months
Population: 13 patients were Smith negative at entry.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gardasil Vaccine | Induction or Increase of Autoantibodies (Conversion From Negative Smith to Positive Smith) | 0 Participants |