Ignite Creation Date:
2025-12-24 @ 7:35 PM
Ignite Modification Date:
2026-01-04 @ 10:44 AM
Study NCT ID:
NCT03069703
Status:
COMPLETED
Last Update Posted:
2025-11-20
First Post:
2017-02-27
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Innovative Anti-pneumococcal Vaccine Strategies in Patients With ANCA-associated Vasculitis Receiving Rituximab Therapy
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Study Overview
Official Title:
Multicenter Randomized Controlled Trial Comparing Immunogenicity and Safety of Two Innovative Anti-pneumococcal Vaccine Strategies to Standard Vaccination Regimen in Patients With ANCA-associated Vasculitis Receiving Rituximab Therapy
Status:
COMPLETED
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PNEUMOVAS
Brief Summary:
The study hypothesis is that a "reinforced" pneumococcal combined vaccine strategy in patients with ANCA-associated vasculitides treated with rituximab will induce a better immune response than the current standard regimen, with an acceptable safety profile.
This study therefore aims at evaluating the immunogenicity and safety of two "reinforced" innovative pneumococcal vaccine regimen \[one double dose at day0 and one double dose at day7 or a quadruple dose of 13-valent anti-pneumococcal conjugate vaccine (PCV13) followed by one dose of 23-valent unconjugated vaccine (PPV23) at month 5\], compared to the standard regimen (one dose of PCV13 followed by one dose of PPV23 at month 5), in patients with ANCA-associated vasculitides receiving rituximab therapy.
This study therefore aims at evaluating the immunogenicity and safety of two "reinforced" innovative pneumococcal vaccine regimen \[one double dose at day0 and one double dose at day7 or a quadruple dose of 13-valent anti-pneumococcal conjugate vaccine (PCV13) followed by one dose of 23-valent unconjugated vaccine (PPV23) at month 5\], compared to the standard regimen (one dose of PCV13 followed by one dose of PPV23 at month 5), in patients with ANCA-associated vasculitides receiving rituximab therapy.
Detailed Description:
Description of research methodology
Experimental plan This is a comparative, multicenter, prospective, randomized, open label, phase 2 trial in France, comparing two innovative "reinforced" anti-pneumococcal vaccine strategies to standard vaccination regimen in patients with ANCA-associated vasculitides receiving rituximab therapy.
Participants will be randomized 1:1:1 to three parallel arms to receive:
* Arm A (standard vaccination regimen): prime-boost strategy combining a single dose of 13-valent pneumococcal conjugate vaccine (Prevenar, PCV13) at Day 0 (lying within a window of ± 2 days of the first infusion of rituximab), followed by a single dose of 23-valent unconjugated vaccine (Pneumovax, PPV23) at month 5 (M5)
* Arm B (innovative vaccine strategy 1): prime-boost strategy combining 2 doses of PCV13 at Day 0 and 2 doses of PCV13 at Day 7, followed by a single dose of PPV23 at M5
* Arm C (innovative vaccine strategy 2): prime-boost strategy combining 4 doses of PCV13 at Day 0, followed by a single dose of PPV23 at M5
All participants will receive rituximab at 375 mg/m2/week for 4 consecutive weeks, at Days 0 ± 2 days, Day 7 ± 2 days, Day 14 ± 2 days and Day 21 ± 2 days, as induction therapy of vasculitis flare, followed by 500 mg-rituximab infusion every 6 months as maintenance therapy, i.e. at Month 6, Month 12 and Month 18 (Stone, NEJM, 2010, Jones, NEJM, 2010; Guillevin, NEJM, 2014), as recommended.
Day 0 will be defined as the first vaccine injection (within ± 2 days of the first infusion of rituximab).
PCV13 vaccine injections will be performed at Day 0, and at Day 7 ± 1 day in the Arm B. PPV23 injections will be performed at M5 ± 7 days in all arms.
Analysis of immune responses will be performed in a centralized laboratory blinded for the trial arm, by ELISA at Day 0 (pre-vaccination sample), M1, M5, M6, M12, and M18 for the 12 serotypes common to both conjugate and unconjugated vaccines, by OPA at Day 0, M6, M12, and M18 for the 12 serotypes common to both conjugate and unconjugated vaccines, and by ELISA at Day 0 and M6 for the 3 specific serotypes of PPV23.
Safety monitoring Relevant adverse events related to vaccination will be continuously monitored throughout the trial, and pausing rules have been specified in the protocol that trigger an ad-hoc iDSMB meeting in case of any safety concern
Number of participating centres
This multicenter research will involve the participation of the French Vasculitis Study Group (FVSG) network, which includes more than 100 clinical departments involved in the management of ANCA-associated vasculitides.
As previous trials conducted by the FVSG on this topic, around 50 centers will participate in the PNEUMOVAS research.
Randomization Participants who fulfill all eligibility criteria for the study will be enrolled and randomized in a ratio of 1:1:1 between the three different parallel arms.
Randomization will be stratified on: personal history of PPV23 injection and age (≥ 65 or \< 65 years).
Blinding methods and provisions put in place to maintain blinding
Trial participants and site staff are not blinded to the vaccine arm. The central laboratory performing the immunogenicity assessment (ELISA and OPA) will be blinded for the trial arm in order to limit measurement bias.
Experimental plan This is a comparative, multicenter, prospective, randomized, open label, phase 2 trial in France, comparing two innovative "reinforced" anti-pneumococcal vaccine strategies to standard vaccination regimen in patients with ANCA-associated vasculitides receiving rituximab therapy.
Participants will be randomized 1:1:1 to three parallel arms to receive:
* Arm A (standard vaccination regimen): prime-boost strategy combining a single dose of 13-valent pneumococcal conjugate vaccine (Prevenar, PCV13) at Day 0 (lying within a window of ± 2 days of the first infusion of rituximab), followed by a single dose of 23-valent unconjugated vaccine (Pneumovax, PPV23) at month 5 (M5)
* Arm B (innovative vaccine strategy 1): prime-boost strategy combining 2 doses of PCV13 at Day 0 and 2 doses of PCV13 at Day 7, followed by a single dose of PPV23 at M5
* Arm C (innovative vaccine strategy 2): prime-boost strategy combining 4 doses of PCV13 at Day 0, followed by a single dose of PPV23 at M5
All participants will receive rituximab at 375 mg/m2/week for 4 consecutive weeks, at Days 0 ± 2 days, Day 7 ± 2 days, Day 14 ± 2 days and Day 21 ± 2 days, as induction therapy of vasculitis flare, followed by 500 mg-rituximab infusion every 6 months as maintenance therapy, i.e. at Month 6, Month 12 and Month 18 (Stone, NEJM, 2010, Jones, NEJM, 2010; Guillevin, NEJM, 2014), as recommended.
Day 0 will be defined as the first vaccine injection (within ± 2 days of the first infusion of rituximab).
PCV13 vaccine injections will be performed at Day 0, and at Day 7 ± 1 day in the Arm B. PPV23 injections will be performed at M5 ± 7 days in all arms.
Analysis of immune responses will be performed in a centralized laboratory blinded for the trial arm, by ELISA at Day 0 (pre-vaccination sample), M1, M5, M6, M12, and M18 for the 12 serotypes common to both conjugate and unconjugated vaccines, by OPA at Day 0, M6, M12, and M18 for the 12 serotypes common to both conjugate and unconjugated vaccines, and by ELISA at Day 0 and M6 for the 3 specific serotypes of PPV23.
Safety monitoring Relevant adverse events related to vaccination will be continuously monitored throughout the trial, and pausing rules have been specified in the protocol that trigger an ad-hoc iDSMB meeting in case of any safety concern
Number of participating centres
This multicenter research will involve the participation of the French Vasculitis Study Group (FVSG) network, which includes more than 100 clinical departments involved in the management of ANCA-associated vasculitides.
As previous trials conducted by the FVSG on this topic, around 50 centers will participate in the PNEUMOVAS research.
Randomization Participants who fulfill all eligibility criteria for the study will be enrolled and randomized in a ratio of 1:1:1 between the three different parallel arms.
Randomization will be stratified on: personal history of PPV23 injection and age (≥ 65 or \< 65 years).
Blinding methods and provisions put in place to maintain blinding
Trial participants and site staff are not blinded to the vaccine arm. The central laboratory performing the immunogenicity assessment (ELISA and OPA) will be blinded for the trial arm in order to limit measurement bias.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2016-002888-33 | EUDRACT_NUMBER | None | View |