Human Papilloma VirusPhase 3NCT03525210
Study of Safety, Tolerability and Immunogenicity of Gardasil®9 in Immunocompromised Patients
A Phase 3 study testing 9-valent HPV vaccine in people with Human Papilloma Virus and Hiv, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
Patients with immunodeficiencies are at increased risk of developing persistent HPV infection and as such HPV-related disease (genital warts and cancer). In this study HIV-patients and SOT-patients will receive 3 doses of Gardasil®9. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Human Papilloma Virus, Hiv, Organ Transplants
- What is being tested?
- 9-valent HPV vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 271 participants
- Where
- 1 siteBelgium
- Study dates
- 4 Apr 2018to 15 Jul 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Independent Ethics Committee (IEC)-approved written informed consent form (ICF) must be obtained from the subject prior to any study-related procedures (including discontinuation of prohibited medication, if applicable) by the subject is given as required by local law.
- Subject (man or woman) is between the age of 18 years and 0 days and 45 years and 365 days for HIV patients, between 18 years and 0 days and 55 years and 365 days for transplant patients at time of signing the ICF
- Subject is able to understand and adhere to the study procedures (e.g., is not planning to relocate far from the investigational centre during the study period); is able to read, understand, and complete the vaccination diary; is able to understand the risks involved with the study; and voluntarily agrees to participate in the study by giving written informed consent.
- * Since the first day of their last menstrual period through Day 1, female subjects have not had sex with males or has had sex with males and used effective contraception with no failures (an example of a failure is a male condom that ruptures during sexual intercourse). Effective contraception is defined as a marketed, approved contraceptive product that the subject has used per the manufacturer's instructions with every act of sexual intercourse. The subject understands and agrees that during the Day 1 through Month 7 period, she should not have sexual intercourse with males without effective contraception. The use of the rhythm method alone, withdrawal alone, and emergency contraception, are not acceptable methods per the protocol. Subjects who have reached menopause, undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation are eligible without the use of contraceptives. Postmenopausal status is defined as: (1) No menses for >1 year but <3 years and confirmed by follicle stimulating hormone (FSH) levels elevated into the postmenopausal range, or (2) no menses for at least 3 years.
- * Subject has had no temperature ≥37.8°C within 24 hours prior to the first injection.
- Patient considerations
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- HIV patients: have CD4+ T cell count of >200 cells/mm² at the last control (less than 12 months ago).
- SOT patients received their organ transplantation ≥12 months prior to vaccination and has been stable in the past 6 months (i.e. no acute rejection or other immunological reactions).
- Apart from having HIV or received a solid organ transplant, the subject is in stable condition (i.e. no graft-versus-host disease or other immunological reactions) and is judged to be in good physical health on the basis of medical history, physical examination (if deemed necessary), and laboratory testing
- Subject agrees to provide study personnel with a primary telephone number as well as an alternate telephone number for follow-up purposes.
Who cannot join
- Subject has a history of an abnormal Pap test or abnormal cervical biopsy results (showing cervical intraepithelial neoplasia or worse) or cervical disease (i.e., surgical treatment for cervical lesions).
- Subject has history of genital warts, Vulvar Intraepithelial Neoplasia or Vaginal Intraepithelial Neoplasia.
- Subject has a history of a positive test for HPV.
- Subject has a history of known prior vaccination with an HPV vaccine, i.e., received a marketed HPV vaccine, or has participated in an HPV vaccine clinical study and has received either active agent or placebo.
- Subject is pregnant (as determined by serum or urine pregnancy test).
- Subject is, at the time of signing ICF, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems as a result of alcohol use.
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- Subject has a history of severe allergic reaction, including known allergy to any vaccine component, including aluminum, yeast, or BENZONASE® (nuclease, Nycomed [used to remove residual nucleic acids from this and other vaccines]) (e.g., swelling of the mouth and throat, difficulty breathing, hypotension or shock) that met the criteria for serious adverse experiences defined in this protocol.
- Patient's condition
- Exclusion criterion only for HIV patients: Subject has had a splenectomy, or has been diagnosed as having a congenital immunodeficiency, lymphoma, leukaemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune or immunosuppressive condition, or has a history of any disease, which, in the investigator's opinion, may confound the results of the study or pose an additional risk to the subject.
- Exclusion criterion only for SOT patients: Subject has had a splenectomy, or has been diagnosed as having a congenital or acquired immunodeficiency, HIV infection, lymphoma, leukaemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune or immunosuppressive condition, or has a history of any disease, which, in the investigator's opinion, may confound the results of the study or pose an additional risk to the subject.
- Patient's medication
- Exclusion criterion only for HIV patients: Subject is receiving or has received in the year prior to enrolment the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (tumour necrosis factor-α antagonists, monoclonal antibody therapies (including rituximab [Rituxan]), intravenous gamma globulin, antilymphocyte sera, or other therapy known to interfere with the immune response. With regard to systemic corticosteroids, a subject will be excluded if she is currently receiving steroid therapy, has recently (defined as within 2 weeks of enrolment) received such therapy, or has received 2 or more courses of high dose corticosteroids (≥20mg/day of prednisone [or equivalent] orally or parenterally) lasting at least 1 week in duration in the year prior to enrolment. Subjects using inhaled, nasal, or topical corticosteroids are considered eligible for the study
- Exclusion criterion only for SOT patients: Subject is receiving or has received in the year prior to enrolment the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (tumour necrosis factor-α antagonists, monoclonal antibody therapies (including rituximab [Rituxan]) ,intravenous gamma globulin or antilymphocyte sera.
- Subject has received any immune globulin or blood-derived product within the 3 months prior to the Day 1 vaccination, or plans to receive any such product during Day 1 through Month 7 of the study.
- Subject has thrombocytopenia or other coagulation disorder that would contraindicate intramuscular injections.
- * Subject has received inactivated vaccines within 14 days prior to the Day 1 vaccination or has received replicating (live) vaccines within 28 days prior to the Day 1 vaccination. The administration of the inactivated influenza vaccine is allowed 7 days prior to or after each study vaccine.
- Subject is concurrently enrolled in a clinical study of investigational agent.
- Subject has a history or current condition of which the investigator believes that it might interfere with the study vaccines.
- Subject has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
- Subject is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label Phase III Study to Investigate the Safety, Tolerability and Immunogenicity of a Nine-valent Human Papillomavirus (HPV) Vaccine (Gardasil®9) in Solid Organ Transplant Recipients and HIV-infected Patients
Patients with immunodeficiencies are at increased risk of developing persistent HPV infection and as such HPV-related disease (genital warts and cancer).
In this study HIV-patients and SOT-patients will receive 3 doses of Gardasil®9. Safety, tolerability and immunogenicity will be evaluated up to one month following the 3rd and last dose of Gardasil®9.
Read the detailed description
This is a single-center, open-label study on safety, tolerability and immunogenicity of Gardasil®9 in 18 to 45 year-old HIV patients, in 18 to 55 year-old solid-organ transplant (SOT) patients.
This study will enrol 140 HIV patients with CD4+ (cluster of differentiation 4) count of >200cells/mm² and 170 SOT patients, all of whom have not yet received a prophylactic HPV vaccine. The 170 SOT patients will be equally divided over 3 different SOT patient groups, namely heart, lung and kidney transplant patients. Therefore the target is to include approximately 57 heart transplant patients, 57 lung transplant patients and 57 kidney transplant patients. Enrolment in a SOT subgroup will be stopped when 57 patients have been included unless recruitment cannot be achieved within one of the other SOT-patient population.
All enrolled subjects will receive a 3-dose regimen (Day 1, Month 2, and Month 6) of GARDASIL®9. Serum samples will be collected on Day 1 and Month 7 for anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibody determination.. The time point for comparison of immune responses will be Month 7, or approximately 4 weeks after the administration of the third dose. The safety/tolerability profile of the vaccine will be evaluated in all subjects in the study. Safety information will be collected on Day 1 through 1 month following the third vaccination or for a total of approximately 7 months for each subject.
The immunogenicity and the safety data will be analyzed per group of patients. More specifically a separate analysis of HIV and SOT patients is planned, since it is expected that the immunosuppressive therapy of SOT patients might have a more profound effect on immunogenicity following vaccination.
This study will provide a comparison of immunogenicity of Gardasil ®9 in immunocompromised patients, with historical controls (15, 18). The number of subjects to be enrolled in the study was determined based on the primary immunogenicity objective.
- Conditions
- Human Papilloma Virus, Hiv, Organ Transplants
- Being tested
- 9-valent HPV vaccine
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
9-valent HPV vaccineBiological
Also called Gardasil9
Vaccination
| Study group | Role | What they receive |
|---|---|---|
| HIV patients | Other | All HIV patients will receive the study vaccines Receives: Biological: 9-valent HPV vaccine |
| SOT patients | Other | All SOT patients will receive the study vaccines Receives: Biological: 9-valent HPV vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seroconversion Following 3 Doses of 9-valent HPV Vaccines
Seroconversion rates of neutralizing antibodies against each HPV vaccine genotypes (6/11/16/18/31/33/45/52/58) one month after completion of a three doses schedule (0, 2 and 6 months) in patients seronegative at baseline for these antibodies.
Measured: 7 months (for each subject)
Secondary outcomes (1)
Adverse Reactions Following 9-valent HPV Vaccination
Number and percentage of subjects with local and systemic sollicited (up to 7 days following each vaccination) and unsollicited adverse events (up to 1 month after the 3rd HPV vaccine) will be analysed
Measured: 7 months (for each subject)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2018
- Study start4 Apr 2018
- Primary completion1 Sep 2019
- Study completion15 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Human Papilloma VirusStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 271 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Corinne Vandermeulen, MD, PhD, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03525210
- Sponsor's protocol ID
- 503-IC
- Status last verified
- Nov 2020
- First submitted
- 2 May 2018
- Last updated
- 11 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase III Study to Investigate the Safety, Tolerability and Immunogenicity of a Nine-valent Human Papillomavirus (HPV) Vaccine (Gardasil®9) in Solid Organ Transplant Recipients and HIV-infected Patients
- ClinicalTrials.gov ID
- NCT03525210
- Acronym / sponsor ID
- 503-IC
- Conditions
- Human Papilloma Virus, Hiv, Organ Transplants
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 271 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 4 Apr 2018 (actual)
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 15 Jul 2020 (actual)
- First posted
- 15 May 2018 (actual)
- Results
- Posted 11 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with immunodeficiencies are at increased risk of developing persistent HPV infection and as such HPV-related disease (genital warts and cancer).
In this study HIV-patients and SOT-patients will receive 3 doses of Gardasil®9. Safety, tolerability and immunogenicity will be evaluated up to one month following the 3rd and last dose of Gardasil®9.
Detailed description
This is a single-center, open-label study on safety, tolerability and immunogenicity of Gardasil®9 in 18 to 45 year-old HIV patients, in 18 to 55 year-old solid-organ transplant (SOT) patients.
This study will enrol 140 HIV patients with CD4+ (cluster of differentiation 4) count of >200cells/mm² and 170 SOT patients, all of whom have not yet received a prophylactic HPV vaccine. The 170 SOT patients will be equally divided over 3 different SOT patient groups, namely heart, lung and kidney transplant patients. Therefore the target is to include approximately 57 heart transplant patients, 57 lung transplant patients and 57 kidney transplant patients. Enrolment in a SOT subgroup will be stopped when 57 patients have been included unless recruitment cannot be achieved within one of the other SOT-patient population.
All enrolled subjects will receive a 3-dose regimen (Day 1, Month 2, and Month 6) of GARDASIL®9. Serum samples will be collected on Day 1 and Month 7 for anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibody determination.. The time point for comparison of immune responses will be Month 7, or approximately 4 weeks after the administration of the third dose. The safety/tolerability profile of the vaccine will be evaluated in all subjects in the study. Safety information will be collected on Day 1 through 1 month following the third vaccination or for a total of approximately 7 months for each subject.
The immunogenicity and the safety data will be analyzed per group of patients. More specifically a separate analysis of HIV and SOT patients is planned, since it is expected that the immunosuppressive therapy of SOT patients might have a more profound effect on immunogenicity following vaccination.
This study will provide a comparison of immunogenicity of Gardasil ®9 in immunocompromised patients, with historical controls (15, 18). The number of subjects to be enrolled in the study was determined based on the primary immunogenicity objective.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV patients | Other | Biological: 9-valent HPV vaccineAll HIV patients will receive the study vaccines |
| SOT patients | Other | Biological: 9-valent HPV vaccineAll SOT patients will receive the study vaccines |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Independent Ethics Committee (IEC)-approved written informed consent form (ICF) must be obtained from the subject prior to any study-related procedures (including discontinuation of prohibited medication, if applicable) by the subject is given as required by local law.
- Subject (man or woman) is between the age of 18 years and 0 days and 45 years and 365 days for HIV patients, between 18 years and 0 days and 55 years and 365 days for transplant patients at time of signing the ICF
- Subject is able to understand and adhere to the study procedures (e.g., is not planning to relocate far from the investigational centre during the study period); is able to read, understand, and complete the vaccination diary; is able to understand the risks involved with the study; and voluntarily agrees to participate in the study by giving written informed consent.
- * Since the first day of their last menstrual period through Day 1, female subjects have not had sex with males or has had sex with males and used effective contraception with no failures (an example of a failure is a male condom that ruptures during sexual intercourse). Effective contraception is defined as a marketed, approved contraceptive product that the subject has used per the manufacturer's instructions with every act of sexual intercourse. The subject understands and agrees that during the Day 1 through Month 7 period, she should not have sexual intercourse with males without effective contraception. The use of the rhythm method alone, withdrawal alone, and emergency contraception, are not acceptable methods per the protocol. Subjects who have reached menopause, undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation are eligible without the use of contraceptives. Postmenopausal status is defined as: (1) No menses for >1 year but <3 years and confirmed by follicle stimulating hormone (FSH) levels elevated into the postmenopausal range, or (2) no menses for at least 3 years.
- * Subject has had no temperature ≥37.8°C within 24 hours prior to the first injection.
Key exclusion criteria (20 listed)
- Subject has a history of an abnormal Pap test or abnormal cervical biopsy results (showing cervical intraepithelial neoplasia or worse) or cervical disease (i.e., surgical treatment for cervical lesions).
- Subject has history of genital warts, Vulvar Intraepithelial Neoplasia or Vaginal Intraepithelial Neoplasia.
- Subject has a history of a positive test for HPV.
- Subject has a history of known prior vaccination with an HPV vaccine, i.e., received a marketed HPV vaccine, or has participated in an HPV vaccine clinical study and has received either active agent or placebo.
- Subject is pregnant (as determined by serum or urine pregnancy test).
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 |
|---|---|---|
| 9-valent HPV vaccineAlso: Gardasil9Vaccination | Biological | HIV patients, SOT patients |
Primary outcome
Seroconversion Following 3 Doses of 9-valent HPV Vaccines
Time frame: 7 months (for each subject)
Seroconversion rates of neutralizing antibodies against each HPV vaccine genotypes (6/11/16/18/31/33/45/52/58) one month after completion of a three doses schedule (0, 2 and 6 months) in patients seronegative at baseline for these antibodies.
1 secondary outcome
Adverse Reactions Following 9-valent HPV Vaccination
Time frame: 7 months (for each subject)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Corinne Vandermeulen, MD, PhD principal investigator
UZ Leuven
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 9-valent HPV vaccine in people with Human Papilloma Virus and Hiv, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 10 inclusion and 20 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 11 Dec 2020. 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 Belgium. 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?
Yes. Results are posted in the registry (first posted 11 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Seroconversion Following 3 Doses of 9-valent HPV Vaccines (time frame: 7 months (for each subject)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Dec 2020.