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

NCT03069703 | Completed Phase 2 DMC

• 2 other identifiers: P1509642016-002888-33
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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.

Conditions

Invasive Pneumococcal Infection

Keywords

Vaccine; ANCA- associated vasculitides; pneumovax; prevenar; pneumovas

Outcome Measures

Primary Outcomes (1)

• Immunogenicity

  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

  6 months

Secondary Outcomes (2)

• Local and/or systemic solicited reactions 7 days following each vaccination

  18 months

• Any adverse event during the trial related or possibly related to vaccine immunization

  18 months

Other Outcomes (9)

• Any adverse event during the trial related to vaccine immunization and leading to discontinuation of the immunization regimen

  18 months

• Any serious adverse event during the study, regardless of the relationship to vaccine immunisation

  18 months

• Proportion of patients with vasculitis flare according to EULAR criteria during the study period, and time to disease relapse.

  18 months

Study Arms (3)

Prime-boost strategy

ACTIVE COMPARATOR

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)

Biological: PCV13; Biological: PPV23; Drug: Rituximab

Innovative vaccine strategy 1

EXPERIMENTAL

2 doses of PCV13 at Day 0 and 2 doses of PCV13 at Day 7, followed by a single dose of PPV23 at M5

Biological: PCV13; Biological: PPV23; Drug: Rituximab

Innovative vaccine strategy 2

EXPERIMENTAL

4 doses of PCV13 at Day 0, followed by a single dose of PPV23 at M5

Biological: PCV13; Biological: PPV23; Drug: Rituximab

Interventions

PCV13 BIOLOGICAL

one dose of PCV13 at D0 (arm A) or two double doses at D0 and D7 (Arm B) or one quadruple dose at D0 (arm C)

Also known as: Prevenar

Innovative vaccine strategy 1; Innovative vaccine strategy 2; Prime-boost strategy

PPV23 BIOLOGICAL

one dose of PPV23 at M5

Also known as: Pneumovax

Innovative vaccine strategy 1; Innovative vaccine strategy 2; Prime-boost strategy

Rituximab DRUG

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

Innovative vaccine strategy 1; Innovative vaccine strategy 2; Prime-boost strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Participants (males and females) aged of 18 years or older
• 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
• Participants with an active disease defined as a BVAS ≥ 3
• Participants planned to receive rituximab as induction therapy using the recommended regimen (i.e. 375 mg/m2/week for 4 consecutive weeks)
• Participants able to give written informed consent prior to participation in the study
• Participants covered by social security regimen or equivalent

You may not qualify if:

• Participants with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) or other vasculitis
• 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),
• Participants treated with rituximab within the previous 12 months,
• Participants who have received blood, blood products, and/or plasma derivatives including parenteral immunoglobulin preparations in the past 3 months before enrolment.
• Participants treated with new other immunosuppressive or immunomodulatory agents within the previous 3 months (including cyclophosphamide, anti-TNF-alpha, intravenous immunoglobulins, abatacept),
• Participants with vaccination with a conjugate anti-pneumococcal vaccine at any time,
• Participants with vaccination with PPV23 within the previous 3 years,
• 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).
• Pregnant women and lactation,
• Participants with contraindication to use rituximab,
• Participants with contraindication to intramuscular injections (hemophilia, anticoagulant therapy (excepted if subcutaneously), thrombocytopenia \< 50 000/mm3).
• Participants with hypersensitivity to previous vaccination
• Participants with hypersensitivity to aluminium phosphate, phenol or protein CRM197 protein from Corynebacterium diphtheria.
• Participants included in another investigational therapeutic study in the month prior D0. Participation to an observational research is allowed.
• Participants under legal guardianship or incapacitation

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• EUCLID Clinical Trial Platform: collaborator
• Recherche Clinique Paris Descartes Necker Cochin Sainte Anne: collaborator
• CIC 1417 Cochin-Pasteur: collaborator
• Groupe Français d'Etude des Vascularites (GFEV): collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Pôle de Médecine Interne, Centre de référence " Maladies systémiques et autoimmunes rares, en particulier Vascularites nécrosantes et Sclérodermies systémiques " Hôpital Cochin, Assistance Publique-Hôpitaux de Paris

Paris, Paris, 75014, France

Location

Related Publications (5)

• doi:10.1136/ard.2010.137778

  BACKGROUND

• doi:10.1136/ard.2008.088302

  BACKGROUND

• Nazi I, Kelton JG, Larche M, Snider DP, Heddle NM, Crowther MA, Cook RJ, Tinmouth AT, Mangel J, Arnold DM. The effect of rituximab on vaccine responses in patients with immune thrombocytopenia. Blood. 2013 Sep 12;122(11):1946-53. doi: 10.1182/blood-2013-04-494096. Epub 2013 Jul 12.

  PMID: 23851398 BACKGROUND

• doi:10.1016/j.vaccine.2011.04.132

  BACKGROUND

• McGregor JG, Negrete-Lopez R, Poulton CJ, Kidd JM, Katsanos SL, Goetz L, Hu Y, Nachman PH, Falk RJ, Hogan SL. Adverse events and infectious burden, microbes and temporal outline from immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis with native renal function. Nephrol Dial Transplant. 2015 Apr;30 Suppl 1(Suppl 1):i171-81. doi: 10.1093/ndt/gfv045.

  PMID: 25805747 BACKGROUND

Related Links

• Website of the necrotizing vasculitides reference center
• Website of the vaccinology clinical center Pasteur Cochin
• Website of the innovative clinical research network in vaccinology

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Heptavalent Pneumococcal Conjugate Vaccine; Pneumococcal Vaccines; Rituximab

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Vaccines, Combined; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Benjamin TERRIER, MD, PhD

  Pôle de Médecine Interne, Centre de référence " Maladies systémiques et autoimmunes rares, en particulier Vascularites nécrosantes et Sclérodermies systémiques " Hôpital Cochin, Assistance Publique-Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Fréderic BATTEUX, PhD

  Laboratoire d'Immunologie Plateforme d'immunomonitoring vaccinal Hôpital Cochin, Assistance Publique-Hôpitaux de Paris

  STUDY CHAIR

• Odile LAUNAY, MD, PhD

  Centre d'Investigation Clinique Cochin Pasteur Hôpital Cochin, Assistance Publique-Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Matthieu GROH, MD

  Hôpital Foch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The central laboratory performing the immunogenicity assessment (ELISA and OPA) will be blinded for the trial arm in order to limit measurement bias.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2017
• First Posted: March 3, 2017
• Study Start: February 5, 2018
• Primary Completion: November 24, 2020
• Study Completion: November 21, 2021
• Last Updated: November 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)