Common Variable ImmunodeficiencyPhase 2EVADNCT01489618
"Prime Boost" Vaccination Strategy Combining Conjugated Anti- Pneumococcal Vaccine (s0) and Polysaccharide Anti- Pneumococcal Vaccine (s4) Compared to Polysaccharide Anti- Pneumococcal Vaccine Alone (s4) In Patients With Common Variable Immunodeficiency
A Phase 2 study testing PPS and PnCJ PPS in people with Common Variable Immunodeficiency, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial summary
The main objective of this study is to evaluate and to compare the specific antibody response to a " prime-boost " vaccine strategy combining the seven valence pneumococcal conjugate vaccine (PnCj) prime at W0 followed by the administration of the pneumococcal capsular polysaccharide vaccine (PPS) boost at W4, to the… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Common Variable Immunodeficiency
- What is being tested?
- PPS and PnCJ PPS
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2009to Mar 2013
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years and < 65 years
- Common variable immunodeficiency according to the WHO criteria,
- Patients treated with intravenous or subcutaneous immunoglobulin.
- Written informed consent
- Absence of acute infections, or other evolutive diseases related to the (cancer, auto-immune disease…)
Who cannot join
- IgG subclass deficiency
- IgA selective deficiency,
- Other primary humoral deficiency (X-linked agammaglobulinemia, Hyper IgM syndrome),
- Long course treatment with corticosteroids > 5mg per day
- Chemotherapy in the last 3 years,
- Prior pneumococcal vaccination in the last 2 years.
Trial locations and contacts
1 site in 1 country.
France1 site
Service d'Immunologie Clinique Hôpital Henri Mondor
Créteil, 94 010
About this study
Official title: Randomised, Multicentric, Phase ii Study of the Immunogenicity of a "Prime Boost" Vaccination Strategy Combining Conjugated Anti- Pneumococcal Vaccine (s0) and Polysaccharide Anti- Pneumococcal Vaccine (s4) Compared to Polysaccharide Anti- Pneumococcal Vaccine Alone (s4) In Patients With Common Variable Immunodeficiency
The main objective of this study is to evaluate and to compare the specific antibody response to a " prime-boost " vaccine strategy combining the seven valence pneumococcal conjugate vaccine (PnCj) prime at W0 followed by the administration of the pneumococcal capsular polysaccharide vaccine (PPS) boost at W4, to the administration of the pneumococcal capsular polysaccharide vaccine (PPS) alone at W4 in patients with common variable immunodeficiency.
Read the detailed description
Main objective :
The main objective of this study is to evaluate and to compare the specific antibody response to a " prime-boost " vaccine strategy combining the seven valence pneumococcal conjugate vaccine (PnCj) prime at W0 followed by the administration of the pneumococcal capsular polysaccharide vaccine (PPS) boost at W4, to the administration of the pneumococcal capsular polysaccharide vaccine (PPS) alone at W4 in patients with common variable immunodeficiency.
Secondary objectives :
- Evaluation and comparison the specific antibody response to seven pneumococcal serotypes, shared by the PnCj and PPS vaccines (4, 6B, 9V, 14, 18C, 19F, 23F), and two serotypes of the PPS vaccine (1, 5) 4 weeks after the single (W8 for patients from Group 1) or the first vaccination (W4 for patients from group 2).
- Evaluation of the duration of the specific antibody response at week 24
- Evaluation of the T CD4 lymphocyte response (proliferation and cytokine production) to the CRM protein
- Study of the Immunoglobulin V gene repertoire (immunoscope) before and after vaccination.
- Safety of the vaccines
- Effect of the vaccine strategies on the frequency of Streptococcus pneumoniae infections (bronchitis, sinusitis and recurrent upper respiratory tract)
EXPERIMENTAL METHODS
Study design
Randomised, multicentric, controlled phase II study of the immunological efficacy of a "prime boost" strategy combining the sequential administration of the PnjC and PPS anti-pneumococcal vaccines, compared to the administration of the PPS vaccine alone, in patients with common variable immunodeficiency.
After randomisation (at W-4) 72 patients will be assigned to the two following groups:
- Group 1: patients will a single administration of the PPS (one dose at W4). 25 patients will be randomised in this group.
- Group 2: patients will receive a first boost with the PnCj (one dose at W0) and then one administration of the PPS vaccines (one dose at W4). 47 patients will be randomised in this group.
R : 1 :2 (Group1 :2)
The final evaluation of this study is at week 12; i.e 4 weeks after the administration of the PPS vaccine in the two groups of patients. A follow up of patients until week 48 will be proposed to patients in order to evaluate the duration of the antibody response at wek 48.
DURATION OF THE STUDY
- Inclusion period : 18 months
- vaccination period: 2 months
- Patients follow-up : 7 months
Number of patients : 72
PRIMARY AND SECONDARY EFFICACY ENDPOINTS
The pneumococcal conjugate vaccine (PnCj) vaccin contains the following 7 pneumococcal serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F.
The pneumococcal capsular polysaccharide vaccine (PPS) contains 23 pneumococcal serotypes and shares the seven serotypes included in PnCJ.
Primary endpoint :
The primary end point of this study is the proportion of responders to each serotype contained in the PnjC vaccine in the two groups of this study according to 4 categories: 5-7; 3-4; 2-1 and 0. A responder is defined by a rise (at least two fold from baseline) of antibody titers specific to pneumococcal serotypes.
Secondary endpoints :
- The following parameters will be evaluated and compared in the two groups of the study : La réponse immunitaire anticorps vis-à-vis des différents sérotypes vaccinaux communs
- geometric mean of the specific antibody titers
- proportion of patients who experienced an increase of specific antibody levels >1 µg/ml
- Evaluation of the priming effect of the PnCj vaccine in the group 2
- Duration of the specific antibody reponses at week 24
- CD4 T lymphocyte responses to the CRM protein (proliferative and cytokine production) in the two groups of the study at weeks 0, 8 and 12.
- Safety of the vaccines
- Effect of the vaccine stategies on the frequency of Streptococcus pneumoniae infections (bronchitis, sinusitis and recurrent upper respiratory tract)
STATISTICAL CONSIDERATIONS
The initial hypothesis for this study is the superiority of the priming strategy. Expected responses are : 0% in group 1 (PPS alone) and 30% in group 2 (PnCj vace and PPS). The number of patients is based on power of 84%.
The primary end point is the proportion of responders to each serotype contained in the PnCj vaccine in the 2 groups. The percentage of patients in each group will be compared by a Fisher's exact test. Mann-Whitney test and Wilcoxon paired test will be used for the comparison of antibody levels and percentage of responding patients respectively.
- Conditions
- Common Variable Immunodeficiency
- Being tested
- PPS, PnCJ PPS
- Keywords
- Common variable immunodeficiency, pneumococcal vaccine, prime boost
- Medical subject headings
- Common Variable Immunodeficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PPSBiological
POLYSACCHARIDE ANTI- PNEUMOCOCCAL VACCINE
PnCJ PPSBiological
PRIMEBOOST CONJUGATED ANTI- PNEUMOCOCCAL VACCINE (Week 0) POLYSACCHARIDE ANTI- PNEUMOCOCCAL VACCINE (Week 4)
| Study group | Role | What they receive |
|---|---|---|
| PPS | Active comparator | Group 1: patients will a single administration of the PPS (one dose at W4). 25 patients will be randomised in this group. Receives: Biological: PPS |
| PnCJ PPS | Experimental | Group 2: patients will receive a first boost with the PnCj (one dose at W0) and then one administration of the PPS vaccines (one dose at W4). 47 patients will be randomised in this group. Receives: Biological: PnCJ PPS |
What is being measured
The primary outcome is the main question the study is designed to answer.
proportion of responders to each serotype
The primary end point of this study is the proportion of responders to each serotype contained in the PnjC vaccine in the two groups of this study according to 4 categories: 5-7; 3-4; 2-1 and 0. A responder is defined by a rise (at least two fold from baseline) of antibody titers specific to pneumococcal serotypes.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2011 (estimated)
- Study startJun 2009
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: End of production
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Common Variable ImmunodeficiencyStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01489618
- Sponsor's protocol ID
- RBM04-34
- Other IDs
- 2007-003235-23
- Acronym
- EVAD
- Status last verified
- Feb 2016
- First submitted
- 8 Dec 2011
- Last updated
- 24 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Multicentric, Phase ii Study of the Immunogenicity of a "Prime Boost" Vaccination Strategy Combining Conjugated Anti- Pneumococcal Vaccine (s0) and Polysaccharide Anti- Pneumococcal Vaccine (s4) Compared to Polysaccharide Anti- Pneumococcal Vaccine Alone (s4) In Patients With Common Variable Immunodeficiency
- ClinicalTrials.gov ID
- NCT01489618
- Acronym / sponsor ID
- EVAD / RBM04-34
- Conditions
- Common Variable Immunodeficiency
- Keywords
- Common variable immunodeficiency, pneumococcal vaccine, prime boost
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: End of production
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- Jun 2009
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 9 Dec 2011 (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.
The main objective of this study is to evaluate and to compare the specific antibody response to a " prime-boost " vaccine strategy combining the seven valence pneumococcal conjugate vaccine (PnCj) prime at W0 followed by the administration of the pneumococcal capsular polysaccharide vaccine (PPS) boost at W4, to the administration of the pneumococcal capsular polysaccharide vaccine (PPS) alone at W4 in patients with common variable immunodeficiency.
Detailed description
Main objective :
The main objective of this study is to evaluate and to compare the specific antibody response to a " prime-boost " vaccine strategy combining the seven valence pneumococcal conjugate vaccine (PnCj) prime at W0 followed by the administration of the pneumococcal capsular polysaccharide vaccine (PPS) boost at W4, to the administration of the pneumococcal capsular polysaccharide vaccine (PPS) alone at W4 in patients with common variable immunodeficiency.
Secondary objectives :
- Evaluation and comparison the specific antibody response to seven pneumococcal serotypes, shared by the PnCj and PPS vaccines (4, 6B, 9V, 14, 18C, 19F, 23F), and two serotypes of the PPS vaccine (1, 5) 4 weeks after the single (W8 for patients from Group 1) or the first vaccination (W4 for patients from group 2).
- Evaluation of the duration of the specific antibody response at week 24
- Evaluation of the T CD4 lymphocyte response (proliferation and cytokine production) to the CRM protein
- Study of the Immunoglobulin V gene repertoire (immunoscope) before and after vaccination.
- Safety of the vaccines
- Effect of the vaccine strategies on the frequency of Streptococcus pneumoniae infections (bronchitis, sinusitis and recurrent upper respiratory tract)
EXPERIMENTAL METHODS
Study design
Randomised, multicentric, controlled phase II study of the immunological efficacy of a "prime boost" strategy combining the sequential administration of the PnjC and PPS anti-pneumococcal vaccines, compared to the administration of the PPS vaccine alone, in patients with common variable immunodeficiency.
After randomisation (at W-4) 72 patients will be assigned to the two following groups:
- Group 1: patients will a single administration of the PPS (one dose at W4). 25 patients will be randomised in this group.
- Group 2: patients will receive a first boost with the PnCj (one dose at W0) and then one administration of the PPS vaccines (one dose at W4). 47 patients will be randomised in this group.
R : 1 :2 (Group1 :2)
The final evaluation of this study is at week 12; i.e 4 weeks after the administration of the PPS vaccine in the two groups of patients. A follow up of patients until week 48 will be proposed to patients in order to evaluate the duration of the antibody response at wek 48.
DURATION OF THE STUDY
- Inclusion period : 18 months
- vaccination period: 2 months
- Patients follow-up : 7 months
Number of patients : 72
PRIMARY AND SECONDARY EFFICACY ENDPOINTS
The pneumococcal conjugate vaccine (PnCj) vaccin contains the following 7 pneumococcal serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F.
The pneumococcal capsular polysaccharide vaccine (PPS) contains 23 pneumococcal serotypes and shares the seven serotypes included in PnCJ.
Primary endpoint :
The primary end point of this study is the proportion of responders to each serotype contained in the PnjC vaccine in the two groups of this study according to 4 categories: 5-7; 3-4; 2-1 and 0. A responder is defined by a rise (at least two fold from baseline) of antibody titers specific to pneumococcal serotypes.
Secondary endpoints :
- The following parameters will be evaluated and compared in the two groups of the study : La réponse immunitaire anticorps vis-à-vis des différents sérotypes vaccinaux communs
- geometric mean of the specific antibody titers
- proportion of patients who experienced an increase of specific antibody levels >1 µg/ml
- Evaluation of the priming effect of the PnCj vaccine in the group 2
- Duration of the specific antibody reponses at week 24
- CD4 T lymphocyte responses to the CRM protein (proliferative and cytokine production) in the two groups of the study at weeks 0, 8 and 12.
- Safety of the vaccines
- Effect of the vaccine stategies on the frequency of Streptococcus pneumoniae infections (bronchitis, sinusitis and recurrent upper respiratory tract)
STATISTICAL CONSIDERATIONS
The initial hypothesis for this study is the superiority of the priming strategy. Expected responses are : 0% in group 1 (PPS alone) and 30% in group 2 (PnCj vace and PPS). The number of patients is based on power of 84%.
The primary end point is the proportion of responders to each serotype contained in the PnCj vaccine in the 2 groups. The percentage of patients in each group will be compared by a Fisher's exact test. Mann-Whitney test and Wilcoxon paired test will be used for the comparison of antibody levels and percentage of responding patients respectively.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PPS | Active comparator | Biological: PPSGroup 1: patients will a single administration of the PPS (one dose at W4). 25 patients will be randomised in this group. |
| PnCJ PPS | Experimental | Biological: PnCJ PPSGroup 2: patients will receive a first boost with the PnCj (one dose at W0) and then one administration of the PPS vaccines (one dose at W4). 47 patients will be randomised in this group. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years and < 65 years
- Common variable immunodeficiency according to the WHO criteria,
- Patients treated with intravenous or subcutaneous immunoglobulin.
- Written informed consent
- Absence of acute infections, or other evolutive diseases related to the (cancer, auto-immune disease…)
Key exclusion criteria (6 listed)
- IgG subclass deficiency
- IgA selective deficiency,
- Other primary humoral deficiency (X-linked agammaglobulinemia, Hyper IgM syndrome),
- Long course treatment with corticosteroids > 5mg per day
- Chemotherapy in the last 3 years,
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 |
|---|---|---|
| PPSPOLYSACCHARIDE ANTI- PNEUMOCOCCAL VACCINE | Biological | PPS |
| PnCJ PPSPRIMEBOOST CONJUGATED ANTI- PNEUMOCOCCAL VACCINE (Week 0) POLYSACCHARIDE ANTI- PNEUMOCOCCAL VACCINE (Week 4) | Biological | PnCJ PPS |
Primary outcome
proportion of responders to each serotype
Time frame: 8 weeks
The primary end point of this study is the proportion of responders to each serotype contained in the PnjC vaccine in the two groups of this study according to 4 categories: 5-7; 3-4; 2-1 and 0. A responder is defined by a rise (at least two fold from baseline) of antibody titers specific to pneumococcal serotypes.
Results and safety
The study was stopped early (reason given: End of production). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2016.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 PPS and PnCJ PPS in people with Common Variable Immunodeficiency, run by Institut National de la Santé Et de la Recherche Médicale, France 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 5 inclusion and 6 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: stopped early, as of the sponsor's last update on 24 Feb 2016. 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 was stopped early (reason given: End of production). Results are not available in the source record.
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?
proportion of responders to each serotype (time frame: 8 weeks). 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 24 Feb 2016.