TransplantPhase 3NCT00677677
Safety and Immunogenicity of Human Papillomavirus (HPV) Vaccine in Solid Organ Transplant Recipients
A Phase 3 study testing Human papillomavirus quadrivalent vaccine in people with Transplant, run by University of Alberta at 1 site in Canada.
Trial summary
Human papillomavirus (HPV) affects a significant number of transplant patients. In women, human papillomavirus (HPV) causes genital warts, pre-cancerous areas of the cervix, and cervical cancer. In men, the virus can cause warts of the anal and genital areas. Men can also sexually transmit the virus to their partners. Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Transplant
- What is being tested?
- Human papillomavirus quadrivalent vaccine
- Type of treatment
- Vaccines
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- May 2008to Dec 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and female Age ≥ 18 and ≤ 35
- Solid Organ Transplant ≥ 3 months post-transplant
- Outpatient status
Who cannot join
- Unable to comply with protocol
- Previous HPV vaccination
- Anticoagulation (that precludes intramuscular injection)
- Therapy for acute rejection in the past 2 weeks
- Febrile illness in the past 2 weeks
- Active CMV infection
- History of anogenital warts or cervical intraepithelial neoplasia or cervical cancer
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Immunogenicity of Human Papillomavirus (HPV) Vaccine in Solid Organ Transplant Recipients.
Human papillomavirus (HPV) affects a significant number of transplant patients. In women, human papillomavirus (HPV) causes genital warts, pre-cancerous areas of the cervix, and cervical cancer. In men, the virus can cause warts of the anal and genital areas. Men can also sexually transmit the virus to their partners. A patient who has had an organ transplant is at higher risk of infections as well as cancers because of the lifelong immune suppressive medications. HPV vaccination is effective in the prevention of cervical cancer and is now recommended for all females aged 9-26 years by Alberta Health and Wellness and the Canadian National Advisory Committee on Immunization (NACI). However, how well the vaccine works in transplant patients is not known.
This study is being done to look at response of the immune system to HPV vaccine in men and women up to the age of 35 who have had an organ transplant. Men are also included in this study because they have the potential to get anal / genital warts and transmit the virus to their partners. The total duration of the study is three years. Fifty female and male solid organ transplant recipients (lung, heart, liver, kidney, pancreas, small bowel or combined organ transplants) on immunosuppression will be enrolled in the study.
Read the detailed description
Cervical cancer affects a significant proportion of the female population. In Canada, it is estimated that there will be 1,350 new diagnoses of cervical cancer in 2007 and 390 deaths [1]. Human papillomavirus (HPV) is the causative agent in genital warts, cervical intraepithelial neoplasia, and cervical cancer. In this study, the vaccine will also be given to males, because males can develop anogenital warts and can transmit the virus to their partners. HPV is a nonenveloped DNA virus containing early and late genes. Although approximately 40 HPV types can infect the genital tract, only a few cause the majority of disease. For example, cancer-causing HPV includes HPV 16 whereas benign tumours are caused by HPV 6 [2].
HPV vaccine is a quadrivalent vaccine consisting of HPV types 6,11,16,18. Types 16 and 18 are implicated in the majority (~70%) of cervical cancers and at least half of CIN 2 and 3 lesions. Types 6 and 11 cause 90% of genital warts. The vaccine contains virus-like particles (VLPs) of the L1 proteins of the four serotypes and is adjuvanted with aluminum hydroxyphosphate sulphate. The vaccine does not contain live virions and cannot cause HPV disease. It is administered by intramuscular injection in three doses at 0, 2 months, and 6 months [2].
HPV vaccination is effective in the prevention of high grade cervical lesions and is now recommended for all females aged 9-26 years by the Canadian National Advisory Committee on Immunization (NACI) [3]. Although the vaccine is licensed for females, males can also develop anogenital warts and can transmit the virus to their partners. Immunogenicity trials have shown similar response to vaccine in adolescent males compared to females [15]. In addition, if women have been infected with 1-3 out of the four serotypes, vaccination appears to prevent cervical lesions from the remaining serotypes [16]. Therefore, although the vaccine is licensed for women ≤ 26 years old, it may also be applicable to somewhat older women who may not have acquired all four serotypes.
Solid organ transplantation is a life-saving modality; however, patients are on life-long immunosuppression which puts them at increased risk of infections as well as cancers. Studies have shown a high incidence of HPV infection in transplant recipients ranging from 17.5-45% [4-8]. An evaluation of 105 renal transplant recipients showed that 17.5% patients were infected with HPV [5]. Another study of 39 renal transplant recipients screened for HPV showed the presence of HPV in 30.7% of patients, primarily in the cervix [6]. Therefore, the risk of HPV infection has been estimated to be 17 times greater in renal transplant recipients than a matched immunocompetent population. Ano-genital neoplasia, related to HPV, is about 16-20 times more common in transplant recipients [5,6].
Yearly physical examinations of the anogenital area and annual Pap smears are recommended for transplant recipients [9]. However, there are no data on the immunogenicity of quadrivalent HPV vaccine in solid organ transplant recipients and no formal recommendations for vaccination in transplant recipients exist. Given that this is a patient population that is uniquely susceptible to HPV infection and its sequelae, it is important that vaccine immunogenicity be studied in transplant recipients.
- Conditions
- Transplant
- Being tested
- Human papillomavirus quadrivalent vaccine
- Keywords
- Lung transplant, Liver transplant, Kidney transplant, Pancreas transplant, HPV, Human Papillomavirus Quadrivalent Vaccine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human papillomavirus quadrivalent vaccineBiological
Also called Gardasil
Patients meeting the inclusion / exclusion criteria will be enrolled from outpatient transplant clinics. Upon enrolment, baseline serum will be obtained and patients will be given the first dose of vaccine. Two months later, serum will again be obtained and the second dose of vaccine will be administered. Finally, at month 6, serum will be obtained and the third dose of vaccine will be given. The final serum samples will be collected at months 7, 12 and 36. At 48 hours and 7 days after each vaccination, patients will be contacted by telephone for local and systemic adverse effect reporting.
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome will be a 2-fold rise in the type-specific HPV titer for at least one of the four sertypes contained in the vaccine at month 7.
Measured: 36 months
Secondary outcomes (1)
Vaccine adverse events including episodes of rejection up to 1 year after study enrolment. Immunogenicity at 36 months post-vaccination.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2008 (estimated)
- Study startMay 2008
- Primary completionApr 2011
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for TransplantStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deepali Kumar, University of Alberta
- Investigators
- Deepali Kumar, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00677677
- Sponsor's protocol ID
- 7350
- Status last verified
- Dec 2014
- First submitted
- 12 May 2008
- Last updated
- 1 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Barr E, Tamms G. Quadrivalent human papillomavirus vaccine. Clin Infect Dis. 2007 Sep 1;45(5):609-7. doi: 10.1086/520654. Epub 2007 Jul 25.
PubMed 17682997FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27. doi: 10.1056/NEJMoa061741.
PubMed 17494925Human papillomavirus infection. Am J Transplant. 2004 Nov;4 Suppl 10:95-100. doi: 10.1111/j.1600-6135.2004.00732.x. No abstract available.
PubMed 15504222Kumar D, Unger ER, Panicker G, Medvedev P, Wilson L, Humar A. Immunogenicity of quadrivalent human papillomavirus vaccine in organ transplant recipients. Am J Transplant. 2013 Sep;13(9):2411-7. doi: 10.1111/ajt.12329. Epub 2013 Jul 9.
PubMed 23837399
Study at a glance
From the registry record, last updated by the sponsor on 1 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Immunogenicity of Human Papillomavirus (HPV) Vaccine in Solid Organ Transplant Recipients.
- ClinicalTrials.gov ID
- NCT00677677
- Acronym / sponsor ID
- 7350
- Conditions
- Transplant
- Keywords
- Lung transplant, Liver transplant, Kidney transplant, Pancreas transplant, HPV, Human Papillomavirus Quadrivalent Vaccine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 14 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Human papillomavirus (HPV) affects a significant number of transplant patients. In women, human papillomavirus (HPV) causes genital warts, pre-cancerous areas of the cervix, and cervical cancer. In men, the virus can cause warts of the anal and genital areas. Men can also sexually transmit the virus to their partners. A patient who has had an organ transplant is at higher risk of infections as well as cancers because of the lifelong immune suppressive medications. HPV vaccination is effective in the prevention of cervical cancer and is now recommended for all females aged 9-26 years by Alberta Health and Wellness and the Canadian National Advisory Committee on Immunization (NACI). However, how well the vaccine works in transplant patients is not known.
This study is being done to look at response of the immune system to HPV vaccine in men and women up to the age of 35 who have had an organ transplant. Men are also included in this study because they have the potential to get anal / genital warts and transmit the virus to their partners. The total duration of the study is three years. Fifty female and male solid organ transplant recipients (lung, heart, liver, kidney, pancreas, small bowel or combined organ transplants) on immunosuppression will be enrolled in the study.
Detailed description
Cervical cancer affects a significant proportion of the female population. In Canada, it is estimated that there will be 1,350 new diagnoses of cervical cancer in 2007 and 390 deaths [1]. Human papillomavirus (HPV) is the causative agent in genital warts, cervical intraepithelial neoplasia, and cervical cancer. In this study, the vaccine will also be given to males, because males can develop anogenital warts and can transmit the virus to their partners. HPV is a nonenveloped DNA virus containing early and late genes. Although approximately 40 HPV types can infect the genital tract, only a few cause the majority of disease. For example, cancer-causing HPV includes HPV 16 whereas benign tumours are caused by HPV 6 [2].
HPV vaccine is a quadrivalent vaccine consisting of HPV types 6,11,16,18. Types 16 and 18 are implicated in the majority (~70%) of cervical cancers and at least half of CIN 2 and 3 lesions. Types 6 and 11 cause 90% of genital warts. The vaccine contains virus-like particles (VLPs) of the L1 proteins of the four serotypes and is adjuvanted with aluminum hydroxyphosphate sulphate. The vaccine does not contain live virions and cannot cause HPV disease. It is administered by intramuscular injection in three doses at 0, 2 months, and 6 months [2].
HPV vaccination is effective in the prevention of high grade cervical lesions and is now recommended for all females aged 9-26 years by the Canadian National Advisory Committee on Immunization (NACI) [3]. Although the vaccine is licensed for females, males can also develop anogenital warts and can transmit the virus to their partners. Immunogenicity trials have shown similar response to vaccine in adolescent males compared to females [15]. In addition, if women have been infected with 1-3 out of the four serotypes, vaccination appears to prevent cervical lesions from the remaining serotypes [16]. Therefore, although the vaccine is licensed for women ≤ 26 years old, it may also be applicable to somewhat older women who may not have acquired all four serotypes.
Solid organ transplantation is a life-saving modality; however, patients are on life-long immunosuppression which puts them at increased risk of infections as well as cancers. Studies have shown a high incidence of HPV infection in transplant recipients ranging from 17.5-45% [4-8]. An evaluation of 105 renal transplant recipients showed that 17.5% patients were infected with HPV [5]. Another study of 39 renal transplant recipients screened for HPV showed the presence of HPV in 30.7% of patients, primarily in the cervix [6]. Therefore, the risk of HPV infection has been estimated to be 17 times greater in renal transplant recipients than a matched immunocompetent population. Ano-genital neoplasia, related to HPV, is about 16-20 times more common in transplant recipients [5,6].
Yearly physical examinations of the anogenital area and annual Pap smears are recommended for transplant recipients [9]. However, there are no data on the immunogenicity of quadrivalent HPV vaccine in solid organ transplant recipients and no formal recommendations for vaccination in transplant recipients exist. Given that this is a patient population that is uniquely susceptible to HPV infection and its sequelae, it is important that vaccine immunogenicity be studied in transplant recipients.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Male and female Age ≥ 18 and ≤ 35
- Solid Organ Transplant ≥ 3 months post-transplant
- Outpatient status
Key exclusion criteria (7 listed)
- Unable to comply with protocol
- Previous HPV vaccination
- Anticoagulation (that precludes intramuscular injection)
- Therapy for acute rejection in the past 2 weeks
- Febrile illness in the past 2 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Human papillomavirus quadrivalent vaccineAlso: GardasilPatients meeting the inclusion / exclusion criteria will be enrolled from outpatient transplant clinics. Upon enrolment, baseline serum will be obtained and patients will be given the first dose of vaccine. Two months later, serum will again be obtained and the second dose of vaccine will be administered. Finally, at month 6, serum will be obtained and the third dose of vaccine will be given. The final serum samples will be collected at months 7, 12 and 36. At 48 hours and 7 days after each vaccination, patients will be contacted by telephone for local and systemic adverse effect reporting. | Biological | – |
Primary outcome
The primary outcome will be a 2-fold rise in the type-specific HPV titer for at least one of the four sertypes contained in the vaccine at month 7.
Time frame: 36 months
1 secondary outcome
Vaccine adverse events including episodes of rejection up to 1 year after study enrolment. Immunogenicity at 36 months post-vaccination.
Time frame: 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jan 2015.
- Background: PubMed 17682997Barr E, Tamms G. Quadrivalent human papillomavirus vaccine. Clin Infect Dis. 2007 Sep 1;45(5):609-7. doi: 10.1086/520654. Epub 2007 Jul 25.
- Background: PubMed 17494925FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27. doi: 10.1056/NEJMoa061741.
- Background: PubMed 15504222Human papillomavirus infection. Am J Transplant. 2004 Nov;4 Suppl 10:95-100. doi: 10.1111/j.1600-6135.2004.00732.x. No abstract available.
- Derived from this study: PubMed 23837399Kumar D, Unger ER, Panicker G, Medvedev P, Wilson L, Humar A. Immunogenicity of quadrivalent human papillomavirus vaccine in organ transplant recipients. Am J Transplant. 2013 Sep;13(9):2411-7. doi: 10.1111/ajt.12329. Epub 2013 Jul 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deepali Kumar, MD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Human papillomavirus quadrivalent vaccine in people with Transplant, run by University of Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome will be a 2-fold rise in the type-specific HPV titer for at least one of the four sertypes contained in the vaccine at month 7. (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00677677, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jan 2015.