Clinical Trial: Innovative Anti-pneumococcal Vaccine Strategies in Patients With ANCA-associated Vasculitis Receiving Rituximab Therapy

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Multicenter Randomized Controlled Trial Comparing Immunogenicity and Safety of Two Innovative Anti-pneumococcal Vaccine Strategies to Standard Vaccination Regimen in Patients With The study hypothesis is that a "reinforced" pneumococcal combined vaccine strategy in patients with ANCRA-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 [a double 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 Summary:

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 1 (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 (Pneumo 23, PPV23) at month 5 (M5)
• Arm 2 (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 3 (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).

Immune response at M6 against 12 pneumococcal serotypes, according to four ordered categories of response: positive response to 0-3, 4-6, 7-9, or 10-12 serotypes common to the PCV13 and PPV23 vaccines. This endpoint will be analyzed as the number and proportion of participants in each of the four response categories using a proportional odds model