Invasive Pneumococcal InfectionsPhase 2DREVACNCT02274415
Immunogenicity Study of an Anti-pneumococcal Vaccination Strategy in Patients With Sickle Cells Disease
A Phase 2 study testing Vaccination with the combined vaccine (Prevenar13 ®) and Vaccination with the polysaccharide vaccine (Pneumo 23 ®) in people with Invasive Pneumococcal Infections and Sickle Cells Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Streptococcus pneumoniae is the major cause of bacterial infection in patients with sickle cells disease. The 23-valent pneumococcal polysaccharide vaccine (PSV) is supposed to be poorly immunogenic in these patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Pneumococcal Infections, Sickle Cells Disease
- What is being tested?
- Vaccination with the combined vaccine (Prevenar13 ®) and Vaccination with the polysaccharide vaccine (Pneumo 23 ®)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 1 siteFrance
- Study dates
- 16 Sep 2013to 10 Apr 2019
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Adult patient with sickle cell anemia (SS homozygous, SC heterozygous compound Sbetathal heterozygous)
Who cannot join
- Heterozygous sickle cell anemia
- Active infection
- Hypersensitivity known or suspected to Prevenar 13® or to Pneumo 23® or to any of the excipients included in the formulation or in the administration system
- Coagulation abnormality indicating against an intramuscular injection (Platelets <50 000 or TP<50%)
- Current chemotherapy or radiotherapy, except for using Siklos®/Hydrea® in the context of sickle cell anemia
- Vaccination whatever in the last 2 months before the protocol vaccination, except influenza vaccination (within 30 days)
Show all 14Show fewer
- Vaccination whatever, provided in the first 2 months following the protocol vaccinations, except influenza vaccination (within the first month following the protocol vaccinations))
- History of pneumococcal vaccination with Pneumo 23® in the previous year
- End-stage renal failure(dialyzed patient, clearance<10ml/mn)
- HIV infection at baseline
- Pregnancy or breastfeeding (A dosage of betaHCG will be conducted for women in childbearing age),contraception recommendation the first 8 weeks of the test for women in childbearing age
- Participation in a clinical research protocol using a drug within the month prior to inclusion.
- No medical assurance
- Adults under tutelage
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of the Immunogenicity of a Prime Boost Vaccination Strategy Combining Conjugated Anti-pneumococcal and Polysaccharide Anti-pneumococcal Vaccine Compared to Polysaccharide Anti -Pneumococcal Vaccine Alone in Patients With Sickle Cells Disease
Streptococcus pneumoniae is the major cause of bacterial infection in patients with sickle cells disease.
The 23-valent pneumococcal polysaccharide vaccine (PSV) is supposed to be poorly immunogenic in these patients. We want to evaluate whether a prime with a 13-valent pneumococcal conjugate vaccine (PCV), able to induce immunologic memory, would improve the immune response against SP polysaccharides (SPP).
Read more
Primary objective: To evaluate and compare the specific antibody response to a prime-boost vaccine strategy combining PCV prime at W0 followed by the administration of PSV boost at W4, to the administration of PSV alone at W4 in patients with sickle cells disease.
Secondary objectives: Evaluation and comparison of the specific antibody response to the thirteen pneumococcal serotypes shared by the PCV and PSV vaccines, 4 weeks after the single PSV vaccination for patients from Group 1 or 4 weeks after the boost PSV vaccination for patients from group 2. Evaluation of the duration of the specific antibody response at W24 and 96. Evaluation of the T CD4 lymphocyte response to the CRM 197 protein. Safety of the vaccines.
Study Design: Randomised, monocentric, controlled phase II study of the immunological efficacy of a prime boost strategy combining the sequential administration of the PCV and PSV, compared to the administration of the PSV alone. 180 adults patients with sickle cells disease will be included. The primary endpoint : proportion of responders at W8 to at least 10 of thirteen serotypes. Secondary endpoints : Proportion of responders at W8 according to 4 categories of responders: 5-7; 3-4; 2-1 and 0. Evaluation of the pneumococcal opsonophagocytic activity (OPA) at baseline and W8 for each serotype, defined as the proportion of patients with OPA > 1:8 geometric mean of the specific antibody titers proportion of patients who experienced an increase of specific antibody levels 1 g/ml. Evaluation of the priming effect of the PCV vaccine in the group 1. Duration of the specific antibody responses at week 24 and W96. CD4 T lymphocyte responses to the CRM 197 protein (proliferative and cytokine production) at weeks 0, 8 and 12. Safety of the vaccines frequency of Streptococcus pneumoniae infections.
Statistical Considerations: With a sample size of 180 patients, and a randomization ration of 1:1, the study will have a power of at least 90% to show a difference of 25% category between the group receiving PCV and PSV vs the group receiving PSV alone (two-sided type I error = 5%). The primary comparison between both groups will be performed using a Chi2 test for independent groups or a Fisher exact test where appropriate.
- Being tested
- Vaccination with the combined vaccine (Prevenar13 ®), Vaccination with the polysaccharide vaccine (Pneumo 23 ®)
- Keywords
- Streptococcus pneumoniae, Sickle cell disease, Immunogenicity, Antibody response
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaccination with the combined vaccine (Prevenar13 ®)Biological
Vaccination with the polysaccharide vaccine (Pneumo 23 ®)Biological
| Study group | Role | What they receive |
|---|---|---|
| PCV vaccine following by the PSV vaccine | Experimental | Group 1: patients will receive a first boost with 13-valent pneumococcal conjugate vaccine (PCV) (one dose at W0) and then one administration of the PSV vaccines (one dose at W4). Receives: Biological: Vaccination with the combined vaccine (Prevenar13 ®); Biological: Vaccination with the polysaccharide vaccine (Pneumo 23 ®) |
| vaccine Pneumo 23 | Active comparator | Group 2: patients will receive a single administration of 23-valent pneumococcal polysaccharide vaccine (PSV) (one dose at W4) Receives: Biological: Vaccination with the polysaccharide vaccine (Pneumo 23 ®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
the proportion of responders at least to 10 of thirteen serotypes
A responder is defined by a rise least two fold from baseline) of antibody titers specific to pneumococcal serotypes;
Measured: at Week 8
Secondary outcomes (7)
Proportion of responders according to 4 categories of responders: 5-7; 3-4; 2-1 and 0.
Response is defined as fold rise of antibody titers (W8 to baseline)
Measured: at Week 8
Evaluation of the pneumococcal opsonophagocytic activity (OPA) for each serotype,
defined as the proportion of patients with OPA > 1:8.
Measured: at baseline and Week 8
The antibody response of the conjugate vaccine
The antibody response to the 13 serotypes of the conjugate vaccine in terms of geometric mean of the specific antibody titers (µg/ml)
Measured: at week 4
The antibody response to the 13 serotypes of the conjugate vaccine in terms of proportion of patients
Measured: at week 4
In the group 1 antibodies titers (µg/ml)
Measured: at week 24 and W96
Number of T CD4 cells responsive to the CRM 197 protein (proliferative and cytokine production) in the two groups of the study
Measured: at weeks 0, 8 and 12.
Number of Streptococcus pneumoniae infections
Number of Streptococcus pneumoniae infections (bacteremia, meningitis, pneumonia, sinusitis, upper respiratory tract infections)
Measured: between baseline and W96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2014 (estimated)
- Study start16 Sep 2013
- Primary completion18 Sep 2017
- Study completion10 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Invasive Pneumococcal InfectionsStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yves LEVY, PHD, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02274415
- Sponsor's protocol ID
- AOM10028
- Other IDs
- P100105
- Acronym
- DREVAC
- Status last verified
- Oct 2017
- First submitted
- 22 Sep 2014
- Last updated
- 9 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Melica G, Bartolucci P, Audureau E, Le Corvoisier P, Habibi A, Gellen J, Selmane D, Michel M, Lacabaratz C, Levy Y. Immunological Efficacy of Pneumococcal Vaccination Including the 13-Valent Pneumococcal Conjugate Vaccine in Adult Patients With Sickle Cell Disease: Results of the Randomized DREVAC Controlled Trial. Clin Infect Dis. 2023 Jun 8;76(11):1949-1958. doi: 10.1093/cid/ciad037.
PubMed 36705266
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Immunogenicity of a Prime Boost Vaccination Strategy Combining Conjugated Anti-pneumococcal and Polysaccharide Anti-pneumococcal Vaccine Compared to Polysaccharide Anti -Pneumococcal Vaccine Alone in Patients With Sickle Cells Disease
- ClinicalTrials.gov ID
- NCT02274415
- Acronym / sponsor ID
- DREVAC / AOM10028
- Keywords
- Streptococcus pneumoniae, Sickle cell disease, Immunogenicity, Antibody response
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 16 Sep 2013 (actual)
- Primary completion
- 18 Sep 2017 (actual)
- Study completion
- 10 Apr 2019 (actual)
- First posted
- 24 Oct 2014 (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.
Streptococcus pneumoniae is the major cause of bacterial infection in patients with sickle cells disease.
The 23-valent pneumococcal polysaccharide vaccine (PSV) is supposed to be poorly immunogenic in these patients. We want to evaluate whether a prime with a 13-valent pneumococcal conjugate vaccine (PCV), able to induce immunologic memory, would improve the immune response against SP polysaccharides (SPP).
Primary objective: To evaluate and compare the specific antibody response to a prime-boost vaccine strategy combining PCV prime at W0 followed by the administration of PSV boost at W4, to the administration of PSV alone at W4 in patients with sickle cells disease.
Secondary objectives: Evaluation and comparison of the specific antibody response to the thirteen pneumococcal serotypes shared by the PCV and PSV vaccines, 4 weeks after the single PSV vaccination for patients from Group 1 or 4 weeks after the boost PSV vaccination for patients from group 2. Evaluation of the duration of the specific antibody response at W24 and 96. Evaluation of the T CD4 lymphocyte response to the CRM 197 protein. Safety of the vaccines.
Study Design: Randomised, monocentric, controlled phase II study of the immunological efficacy of a prime boost strategy combining the sequential administration of the PCV and PSV, compared to the administration of the PSV alone. 180 adults patients with sickle cells disease will be included. The primary endpoint : proportion of responders at W8 to at least 10 of thirteen serotypes. Secondary endpoints : Proportion of responders at W8 according to 4 categories of responders: 5-7; 3-4; 2-1 and 0. Evaluation of the pneumococcal opsonophagocytic activity (OPA) at baseline and W8 for each serotype, defined as the proportion of patients with OPA > 1:8 geometric mean of the specific antibody titers proportion of patients who experienced an increase of specific antibody levels 1 g/ml. Evaluation of the priming effect of the PCV vaccine in the group 1. Duration of the specific antibody responses at week 24 and W96. CD4 T lymphocyte responses to the CRM 197 protein (proliferative and cytokine production) at weeks 0, 8 and 12. Safety of the vaccines frequency of Streptococcus pneumoniae infections.
Statistical Considerations: With a sample size of 180 patients, and a randomization ration of 1:1, the study will have a power of at least 90% to show a difference of 25% category between the group receiving PCV and PSV vs the group receiving PSV alone (two-sided type I error = 5%). The primary comparison between both groups will be performed using a Chi2 test for independent groups or a Fisher exact test where appropriate.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PCV vaccine following by the PSV vaccine | Experimental | Biological: Vaccination with the combined vaccine (Prevenar13 ®), Biological: Vaccination with the polysaccharide vaccine (Pneumo 23 ®)Group 1: patients will receive a first boost with 13-valent pneumococcal conjugate vaccine (PCV) (one dose at W0) and then one administration of the PSV vaccines (one dose at W4). |
| vaccine Pneumo 23 | Active comparator | Biological: Vaccination with the polysaccharide vaccine (Pneumo 23 ®)Group 2: patients will receive a single administration of 23-valent pneumococcal polysaccharide vaccine (PSV) (one dose at W4) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age ≥ 18 years
- Adult patient with sickle cell anemia (SS homozygous, SC heterozygous compound Sbetathal heterozygous)
Key exclusion criteria (14 listed)
- Heterozygous sickle cell anemia
- Active infection
- Hypersensitivity known or suspected to Prevenar 13® or to Pneumo 23® or to any of the excipients included in the formulation or in the administration system
- Coagulation abnormality indicating against an intramuscular injection (Platelets <50 000 or TP<50%)
- Current chemotherapy or radiotherapy, except for using Siklos®/Hydrea® in the context of sickle cell anemia
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 |
|---|---|---|
| Vaccination with the combined vaccine (Prevenar13 ®) | Biological | PCV vaccine following by the PSV vaccine |
| Vaccination with the polysaccharide vaccine (Pneumo 23 ®) | Biological | PCV vaccine following by the PSV vaccine, vaccine Pneumo 23 |
Primary outcome
the proportion of responders at least to 10 of thirteen serotypes
Time frame: at Week 8
A responder is defined by a rise least two fold from baseline) of antibody titers specific to pneumococcal serotypes;
7 secondary outcomes
Proportion of responders according to 4 categories of responders: 5-7; 3-4; 2-1 and 0.
Time frame: at Week 8
Evaluation of the pneumococcal opsonophagocytic activity (OPA) for each serotype,
Time frame: at baseline and Week 8
The antibody response of the conjugate vaccine
Time frame: at week 4
The antibody response to the 13 serotypes of the conjugate vaccine in terms of proportion of patients
Time frame: at week 4
In the group 1 antibodies titers (µg/ml)
Time frame: at week 24 and W96
Number of T CD4 cells responsive to the CRM 197 protein (proliferative and cytokine production) in the two groups of the study
Time frame: at weeks 0, 8 and 12.
Number of Streptococcus pneumoniae infections
Time frame: between baseline and W96
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 9 Sep 2022.
- Derived from this study: PubMed 36705266Melica G, Bartolucci P, Audureau E, Le Corvoisier P, Habibi A, Gellen J, Selmane D, Michel M, Lacabaratz C, Levy Y. Immunological Efficacy of Pneumococcal Vaccination Including the 13-Valent Pneumococcal Conjugate Vaccine in Adult Patients With Sickle Cell Disease: Results of the Randomized DREVAC Controlled Trial. Clin Infect Dis. 2023 Jun 8;76(11):1949-1958. doi: 10.1093/cid/ciad037.
Related trials for Invasive Pneumococcal Infections
RecruitingObservational study
National, Non Interventional Study of Invasive Pneumococcal Disease in Children and Newborns
Pneumococcal Infections, Pneumococcal Conjugate Vaccine
Not yet recruitingObservational study
Epidemiology of Invasive Bacterial Infections in Children With Sickle Cell Disease in France Between 2020 and 2025
Sickle Cell Disease (SCD), Invasive Bacterial Infections
RecruitingPhase 1
Serum Collection Study for Assay Development
Pneumococcal Disease, Invasive, Pneumococcal Disease
Active, not recruitingPhase 2
Phase 2 Trial to Evaluate Safety and Immunogenicity of Inventprise's (IVT) 25-valent Pneumococcal Conjugate Vaccine (IVT PCV-25) in Healthy Infants
Pneumococcal Disease, Invasive
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.
Yves LEVY, PHD, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vaccination with the combined vaccine (Prevenar13 ®) and Vaccination with the polysaccharide vaccine (Pneumo 23 ®) in people with Invasive Pneumococcal Infections and Sickle Cells Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 2 inclusion and 14 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 9 Sep 2022. 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 France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 proportion of responders at least to 10 of thirteen serotypes (time frame: at Week 8). 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 NCT02274415, which also lists 1 linked publication.
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 9 Sep 2022.