Study of Safety, Tolerability and Immunogenicity of Gardasil®9 in Immunocompromised Patients
Condition: Human Papilloma Virus; Hiv; Organ Transplants
MeSH terms: Papilloma
Intervention: 9-valent HPV vaccine
Intervention description: Vaccination
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 271.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

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. Safety,
      tolerability and immunogenicity will be evaluated up to one month following the 3rd and last
      dose of Gardasil®9.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. 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

          3. 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.

          4. * 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.

          5. * Subject has had no temperature ≥37.8°C within 24 hours prior to the first injection.

          6. Patient considerations

               -  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).

          7. 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

          8. Subject agrees to provide study personnel with a primary telephone number as well as
             an alternate telephone number for follow-up purposes.

        Exclusion Criteria:

          1. 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).

          2. Subject has history of genital warts, Vulvar Intraepithelial Neoplasia or Vaginal
             Intraepithelial Neoplasia.

          3. Subject has a history of a positive test for HPV.

          4. 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.

          5. Subject is pregnant (as determined by serum or urine pregnancy test).

          6. 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.

          7. 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.

          8. Patient's condition

               1. 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.

               2. 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.

          9. Patient's medication

               1. 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

               2. 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.

         10. 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.

         11. Subject has thrombocytopenia or other coagulation disorder that would contraindicate
             intramuscular injections.

         12. * 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.

         13. Subject is concurrently enrolled in a clinical study of investigational agent.

         14. Subject has a history or current condition of which the investigator believes that it
             might interfere with the study vaccines.

         15. 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.

         16. 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.