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

• Status: Active, not recruiting
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: CIC 1417 Cochin-Pasteur; CIC Cochin-Pasteur; EUCLID Clinical Trial Platform; EUCLID Clinical Trials Platform; Groupe Français d'Etude des Vascularites (GFEV); Recherche Clinique Paris Descartes Necker Cochin Sainte Anne; URC/CIC Cochin-Necker
• Treatments: Heptavalent Pneumococcal Conjugate Vaccine; Rituximab; Vaccines

Criteria

Inclusion Criteria:

1. Participants with a diagnosis of ANCA-associated vasculitis, either granulomatosis with polyangiitis (GPA, Wegener) or microscopic polyangiitis (MPA), according to ACR 1990 criteria and/or revised Chapel Hill Consensus Conference definitions and/or European Medical Agency algorithm

2. Participants (males and females) aged of 18 years or older

3. Participants with childbearing potential having reliable contraception for all the duration of the study, such as established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that subject); surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation) or true abstinence (when this is in line with the preferred and usual lifestyle of the subject) prior to enrollment at D0

4. Participants with newly-diagnosed disease at the time of inclusion or presenting with a relapse of the disease. For relapsing patients, maintenance therapy at stable dose during the last 3 months will be admitted : prednisone dose ≤10 mg/day, azathioprine dose ≤3 mg/kg/day, methotrexate dose ≤25 mg/week, or mycophenolate mofetil dose ≤3 g/j

5. Participants with an active disease defined as a BVAS ≥ 3

6. Participants planned to receive rituximab as induction therapy using the recommended regimen (i.e. 375 mg/m2/week for 4 consecutive weeks)

7. Participants able to give written informed consent prior to participation in the study

8. Participants covered by social security regimen or equivalent

Exclusion Criteria:

1. Participants with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) or other vasculitis

2. Participants with acute infections or chronic active infections at inclusion visit.

3. Documented positive serology result for HIV, HBV (Ag Hbs), HCV at inclusion.

4. Participants with disease associated with decreased immune response (splenectomy, hematopoietic stem cell transplantation, primary immune deficiency such as common variable immunodeficiency, cancer within the previous 5 years, drepanocytosis),

5. Participants treated with rituximab within the previous 12 months,

6. Participants who have received blood, blood products, and/or plasma derivatives including parenteral immunoglobulin preparations in the past 3 months before enrolment.

7. Participants treated with new other immunosuppressive or immunomodulatory agents within the previous 3 months (including cyclophosphamide, anti-TNF-alpha, intravenous immunoglobulins, abatacept),

8. Participants treated with prednisone dose >10 mg/day for a duration greater than 21 days before inclusion,

9. Participants with vaccination with a conjugate anti-pneumococcal vaccine at any time,

10. Participants with vaccination with PPV23 within the previous 3 years,

11. . Participants who have received any another vaccines within 4 weeks prior to enrolment or who are planning to receive any vaccine within the first 6 months of the study (except annual influenza vaccination and hepatitis B virus vaccination which are permitted before and after each vaccination visit of the study and then allowed at any time during the study follow up).

12. Pregnant women and lactation,

13. Participants with contraindication to use rituximab,

14. Participants with contraindication to intramuscular injections (hemophilia, anticoagulant therapy (excepted if subcutaneously), thrombocytopenia < 50 000/mm3).

15. Participants with hypersensitivity to previous vaccination

16. Participants with hypersensitivity to aluminium phosphate, phenol or protein CRM197 protein from Corynebacterium diphtheria.

17. Participants included in another investigational therapeutic study in the month prior D0. Participation to an observational research is allowed.

18. Participants under legal guardianship or incapacitation