Trial record 2 of 7 for:    Miller Fisher Syndrome

Study Assessing Risk of Autoimmune Diseases in Females (9 - 25 Years) Exposed to Cervarix® in United Kingdom

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01953822
First received: September 26, 2013
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

This is an observational cohort study to assess the risk of autoimmune disease(s) within 12 months of receiving the first dose of Cervarix® in the exposed cohort and over a comparable period in the unexposed cohorts.

This is an alternative study by GSK using the CPRD database in the UK to fulfil the US FDA safety commitment. The UK has had sufficient Cervarix® vaccination coverage during the period mid-September 2008 to 2011 to allow suitable data to be collected.


Condition Intervention
Autoimmune Diseases in Subjects Receiving Cervarix®
Other: Data collection

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: An Observational Cohort Study to Assess the Risk of Autoimmune Diseases in Adolescent and Young Adult Women Aged 9 to 25 Years Exposed to Cervarix® in the United Kingdom

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Occurrence of new onset of confirmed autoimmune disease for neuroinflammatory/ophthalmic autoimmune diseases [ Time Frame: During the period of 1 year following administration of the first dose of Cervarix® (risk period) among an exposed cohort and during an equivalent time period in the unexposed cohorts ] [ Designated as safety issue: No ]
    Neuroinflammatory/ophthalmic autoimmune diseases: -Multiple Sclerosis; -Transverse myelitis; -Optic neuritis; -Guillain-Barré syndrome, including Miller Fisher syndrome and other variants; -Other demyelinating diseases: -Acute disseminated encephalomyelitis, including site specific variants: e.g. non-infectious encephalitis, encephalomyelitis, myelitis, myeloradiculomyelitis; -AI peripheral neuropathies and plexopathies (including chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and polyneuropathies associated with monoclonalgammopathy); -Auto-immune uveitis;

  • Occurrence of new onset of confirmed autoimmune disease for other autoimmune diseases [ Time Frame: During the period of 1 year following administration of the first dose of Cervarix® (risk period) among an exposed cohort and during an equivalent time period in the unexposed cohorts ] [ Designated as safety issue: No ]
    Other autoimmune diseases: -Systemic lupus erythematous; -Autoimmune (AI) disease with rheumatologic conditions: -Rheumatoid arthritis (RA);-Juvenile rheumatoid arthritis (JRA); -Still's disease; -Psoriatic arthritis; -Ankylosing Spondylitis; -AI haematological conditions: -Idiopathic thrombocytopenic purpura (ITP); -AI haemolytic anaemia; -AI endocrine conditions: -Type 1 diabetes mellitus; -AI thyroiditis including Hashimoto's disease, Graves' /Basedows' disease; -Inflammatory bowel / hepatic diseases: -Crohn's diseases; -Ulcerative colitis; -Autoimmune hepatitis;


Secondary Outcome Measures:
  • Occurrence of Guillain Barré syndrome (including Miller Fisher syndrome and other variants), and autoimmune haemolytic anaemia [ Time Frame: Within 2 months following the administration of the first dose of Cervarix® ] [ Designated as safety issue: No ]
  • Occurrence of idiopathic thrombocytopenic purpura (ITP) [ Time Frame: Within six months following the administration of the first dose of Cervarix® ] [ Designated as safety issue: No ]
  • Occurrence of new onset of individual confirmed autoimmune disease [ Time Frame: Within 1 year following the administration of the first dose of Cervarix® ] [ Designated as safety issue: No ]
    Occurrence of multiple sclerosis, transverse myelitis, optic neuritis, other demyelinating diseases, auto-immune uveitis, systemic lupus erythematous (SLE), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), Still's disease, psoriatic arthritis, ankylosing spondylitis, type 1 diabetes mellitus, auto-immune thyroiditis (including Hashimoto's disease, Graves'/Basedows' disease), and inflammatory bowel / hepatic disease (Crohn's disease, ulcerative colitis and autoimmune hepatitis)


Estimated Enrollment: 260000
Study Start Date: October 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Cervarix vaccinated (exposed) female cohort
Female subjects vaccinated with at least one dose of Cervarix® between the ages of 9 to 25 years.
Other: Data collection
Data collection from an existing electronic healthcare databases - Clinical Practice Research Datalink (CPRD) GOLD.
Unexposed historical female cohort
Unexposed female subjects identified from historical data, will be frequency matched for age and practice region identifier to the subjects included in the vaccinated (exposed) cohort.
Other: Data collection
Data collection from an existing electronic healthcare databases - Clinical Practice Research Datalink (CPRD) GOLD.
Unexposed concurrent male cohort
Male population is composed of 9- to 25-year-old male subjects not vaccinated with Cervarix®.
Other: Data collection
Data collection from an existing electronic healthcare databases - Clinical Practice Research Datalink (CPRD) GOLD.
Unexposed historical male cohort
Male population is composed of 9- to 25-year-old male subjects not vaccinated with Cervarix®. Comparison of the unexposed concurrent male cohort with the unexposed historical male cohort will be used as an internal control for changes over time in Clinical Practice Research Datalink (CPRD) GOLD in reporting New Onset of Autoimmune Diseases (NOAD). The male subjects will be frequency matched for age and practice region identifier to the subjects included in the vaccinated (exposed) cohort.
Other: Data collection
Data collection from an existing electronic healthcare databases - Clinical Practice Research Datalink (CPRD) GOLD.

Detailed Description:

GSK's vaccine Cervarix® protects against Human Papilloma Virus Types-16 and 18-related pre-cancerous lesions. GSK is committed by the US Food and Drug Administration (FDA) to conduct a safety study to evaluate the incidence of new neurological and eye-related autoimmune diseases and other pre-specified autoimmune diseases in subjects receiving Cervarix® in the US. Because of the very low Cervarix® uptake in the US, the observational GSK study to address this commitment is due to be stopped, as it will take too long to recruit the target subjects.

The unexposed male cohorts will be enrolled in order to assess a possible change over time in the incidence rate of new onset of autoimmune disease(s) (NOAD) in the UK Clinical Practice Research Datalink General Practitioner OnLine database (CPRD GOLD) independent of Cervarix® introduction. The cohorts will be frequency matched for the age (age class of one year) and practice region identifier at reference date (age at first dose of Cervarix).

Additionally, the reference date (time = 0) for the vaccinated (exposed) cohort will be the date of the first dose of Cervarix® recorded in CPRD GOLD. The reference date for the unexposed (unvaccinated) cohorts will be a date randomly selected among the reference dates of the exposed subjects and minus 3 years for the historical cohorts.

The other observational study model is a self-control case-series (SCCS) analysis for confirmed NOAD in the exposed female cohort, using a risk period of one year after the first Cervarix® dose, a control period of one year and a six month buffer period between risk and control periods.

Human Papillomavirus Bivalent (Types 16 and 18) vaccine (recombinant) exposed cohort was investigated between 1-SEP-2008 and 31-AUG-2010.

The unexposed concurrent male cohort was investigated between 1-SEP-2008 and 31-AUG-2010.

Unexposed historical female and male cohorts were investigated between 1-SEP-2005 and 31-AUG-2007.

  Eligibility

Ages Eligible for Study:   9 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Female population is composed of female subjects vaccinated with Cervarix® between the ages of 9 to 25 years and unexposed female subjects identified from historical data. Male population is composed of 9- to 25-year-old male subjects not vaccinated with Cervarix®.

Criteria

Inclusion Criteria:

Note: Other vaccines are allowed in this study regardless of the time of administration and the time interval between subsequent doses.

Inclusion criteria for the exposed female cohort:

  • Female aged from 9 to 25 years at the reference date (01 September 2008 through 31 August 2010).
  • Recorded in the CPRD GOLD for at least 12 months before the reference date.
  • The first dose of Cervarix received between 01 September 2008 through 31 August 2010, Full date (day/month/year) of Cervarix vaccination(s) available.
  • Subject defined as acceptable in CPRD GOLD.

Inclusion criteria for the unexposed historical female cohort:

  • Female aged 9 to 25 years at the reference date (01 September 2005 through 31 August 2007).
  • Recorded in the CPRD GOLD for at least 12 months before the reference date.
  • Subject defined as acceptable in CPRD GOLD.

Inclusion criteria for the unexposed concurrent male cohort:

  • Male aged 9 to 25 years at the reference date (01 September 2008 through 31 August 2010).
  • Recorded in the CPRD GOLD for at least 12 months before the reference date.
  • Subject defined as acceptable in CPRD GOLD.

Inclusion criteria for the unexposed historical male cohort:

  • Male aged 9 to 25 years at the reference date (01 September 2005 through 31 August 2007).
  • Recorded in the CPRD GOLD for at least 12 months before the reference date.
  • Subject defined as acceptable in CPRD GOLD.

Exclusion Criteria:

Exclusion criteria for all cohorts:

  • Subjects with a diagnostic code of any auto-immune disease during the year prior to the reference date.
  • Subjects who received at least one dose of unspecified HPV vaccine or Gardasil at any time before the reference date.
  • Subjects who have been included in the other cohort.

Exclusion criteria for the non-exposed cohorts:

• Subjects who received any dose of Cervarix at any time before the reference date.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01953822

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01953822     History of Changes
Other Study ID Numbers: 116239
Study First Received: September 26, 2013
Last Updated: June 5, 2014
Health Authority: United Kingdom: Independent Scientific Advisory Committee (ISAC)

Keywords provided by GlaxoSmithKline:
Observational
Cohort
Autoimmune disease
Cervarix®
Women aged 9 to 25 years
United Kingdom

Additional relevant MeSH terms:
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 16, 2014