| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Pneumococcal infection in HIV infected subjects |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061353 |
| E.1.2 | Term | Pneumococcal infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the immune responses 1 month after 3 doses of 13vPnC compared to 1 month after 2 doses of 13vPnC as measured by fold rises of serotype-specific immunoglobulin G (IgG) geometric mean antibody concentrations (GMC) in individuals ≥6 years of age.
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| E.2.2 | Secondary objectives of the trial |
· To evaluate the immune responses 1 month after 3 doses of 13vPnC compared to 1 month after 2 doses of 13vPnC as measured by serotype-specific IgG GMCs in individuals ≥6 years of age.
· To evaluate the immune responses 1 month after 3 doses of 13vPnC compared to 1 month after 2 doses of 13vPnC as measured by serotype-specific opsonophagocytic activity (OPA) geometric mean antibody titers (GMT) and fold rise OPA GMTs in individuals ≥6 years of age.
· To evaluate the immune responses 1 month after 3 doses of 13vPnC compared to 1 month after 2 doses of 13vPnC as measured by serotype-specific IgG GMCs, fold rise IgG GMCs, OPA GMTs and fold rise OPA GMTs in the pediatric subgroup (6 to <18 years of age) and in the adult subgroup (≥18 years of age). |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Male or female subjects aged 6 years or older at the time of enrollment.
2.HIV-infection with viral load <50,000 copies/mL obtained on the most recent 2 occasions within 6 months before article administration.
3.CD4+ T cell count ≥ 200 cells/µL obtained on the most recent 2 occasions within 6 months before test article administration.
4.Receiving stable dose of HAART for at least 6 weeks before test article administration, or not currently receiving any antiretroviral therapy.
5.Subject is naïve to any licensed or experimental pneumococcal vaccine.
6.Determined by medical history, physical examination, and clinical judgment to be eligible for the study. (Note: Subjects with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease 6 weeks before test article administration, are eligible.)
7.Subject or their parent/legal guardian, if appropriate, must be able to complete an electronic diary (e-diary) and complete all relevant study procedures during study participation.
8.Subject is available for the entire study period (approximately 8 months), and who themselves or, where appropriate, whose parent/legal guardian can be contacted by telephone throughout the study.
9.All female and male subjects who are biologically capable of having children must agree to abstinence or commit to the use of a reliable method of birth control from the signing of the informed consent form (ICF) until 3 months after the last dose of test article. A subject is biologically capable of having children even if he or she is using contraceptives, or if his or her sexual partner is sterile or using contraceptives. |
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| E.4 | Principal exclusion criteria |
1.Subject with active immune deficiency syndrome (AIDS) related illness, including opportunistic infections or malignancy.
2.Current illicit substance and/or alcohol abuse.
3.History of active chronic viral hepatitis with biochemical evidence of AST or ALT values greater than 5 times higher than the upper limit of normal within 6 months before enrollment.
4.Previous anaphylactic reaction to any vaccine or vaccine-related component.
5.History of culture-proven invasive disease caused by Streptococcus pneumoniae within 12 months before enrollment.
6.In the opinion of the investigator, unable to receive a vaccination in the deltoid muscle of either arm due to insufficient muscle mass.
7.Pregnant or breastfeeding females, as defined by history or by positive human chorionic gonadotropin (hCG) urine test. A urine pregnancy test must be performed prior to vaccination for all female subjects who are post-menarche and who are not surgically sterile or post-menopausal (>1 year).
8.Subject who is a direct relative (child, grandchild, parent or grandparent) of a study personnel, or is a study personnel.
9.Current residence in a nursing home, long-term care facility or other similar institution, or requirement of semi-skilled nursing care. (Note: An ambulatory subject who is a resident of a retirement home or village is eligible for the trial.)
10.Evidence of dementia or other severe cognitive impairment.
11.Current anticoagulant therapy or a history of bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection (Note: use of antiplatelet drugs such as aspirin and clopidogrel are permitted.)
12.Receipt of any blood products, including immunoglobulin, within 42 days before test article administration until the last blood draw for the study (approximately 4 months after the first test article administration).
13.Use of immunosuppressive agents, to include systemic corticosteroids and cancer chemotherapeutic agents. Use of systemic corticosteroids for 14 days or more is considered immunosuppressive. (Note: such individuals are not eligible to receive test article until at least 28 days after systemic corticosteroid therapy has been discontinued, or for immunosuppressive agents other than corticosteroids, at least 28 days after levels have been reached that are not associated with immunosuppression. Corticosteroids administered by other routes such as by inhalation, topically or intra-articularly are permitted.)
14.Serious chronic disorders or any other disorders that in the investigator’s opinion precludes the subject from participating in the study. (Note: serious chronic disorders include metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, end-stage renal disease with or without dialysis, and clinically unstable cardiac disease.)
15.Participation in another study using an investigational product from 28 days before study enrollment until the end of the study. (Note: participation in purely observational studies is acceptable.)
16.Any major illness/condition that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in, and completion of the study.
17.Any major illness/condition that, in the investigator’s judgment, could preclude the evaluation of the subject’s response to vaccination. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary immunologic comparison of interest is the serotype-specific IgG GMFRs at 1 month after 3 doses of 13vPnC versus that after 2 doses of 13vPnC in subjects ≥6 years of age. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Immune responses after 2 and 3 doses of 13vPnC as measured by serotype-specific igG geometric mean fold rises rises (GMFRs) in all subjects - 1 month after 3 doses of 13vPnC (approx. 3 months)
• Safety of 13vPnC measured by local reactions, systemic events - 14 days post-vaccination doses 1-3
• Safety of 13vPnC measured by AE - Ongoing through study. |
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| E.5.2 | Secondary end point(s) |
• Immune responses after each dose of study vaccine as measured by IgG in all subjects - 1 month post-vaccination dose 1-4
• Immune responses after each dose of study vaccine as measured by IgG in the peaditric & adult subgroups - 1 month post vaccination dose 1-4
• Immune responses after each dose of study vaccine as measured by opsonophagocytic activity in all subjects - 1 ;onth post-vaccination doses 1-4
• Immune responses after each dose of study vaccine as measured by opsonophagocytic activity in the pediatric & adult subgroups - 1 month post-vaccination doses 1-4 |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Immune responses after each dose of study vaccine as measured by IgG in all subjects and in the peaditric & adult subgroups - 1 month post-vaccination dose 1-4
• Immune responses after each dose of study vaccine as measured by opsonophagocytic activity in all subjects and in the pediatric & adult subgroups - 1 month post-vaccination doses 1-4 |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| Trial ends at the last subject's last visit. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
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