Study to Determine if Gardasil Vaccine is Safe and Effective in Lupus Patients (GARDASIL)

Phase I, Safety and Immunogenicity of Gardasil® in Systemic Lupus Erythematosus.

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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Gardasil

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 Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • DCaTS-Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Participants With Adverse Events	Frequency of participants with Vaccine site reactions, Frequency of participants with Non Vaccine Adverse Events,	1,61,66,181,186,211,330 days
Number of Non Vaccine Adverse Events	the number of non vaccine adverse events	1,61,66,181,186,211,330 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion by HPV Serotypes (HPV 6, HPV 11, HPV 16, HPV 18)as Assessed by Geometric Mean Antibody Titer	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	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.
SLE Disease Activity Flares	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.	1,61,66,181,186,211,330 days

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Patricia J Dhar, MD, Wayne State University

Publications and helpful links

General Publications

• Dhar JP, Essenmacher L, Dhar R, Magee A, Ager J, Sokol RJ. The safety and immunogenicity of Quadrivalent HPV (qHPV) vaccine in systemic lupus erythematosus. Vaccine. 2017 May 9;35(20):2642-2646. doi: 10.1016/j.vaccine.2017.04.001. Epub 2017 Apr 9.

Helpful Links

• Clinical Research Services Center, Wayne State University School of Medicine

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: November 14, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimate): December 4, 2012

Study Record Updates

• Last Update Posted (Actual): November 5, 2018
• Last Update Submitted That Met QC Criteria: February 26, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Lupus
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: 0412GARDASIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No individual data will be shared with any researcher, only aggregated de-identified data