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Invasive Pneumococcal InfectionPhase 2PNEUMOVASNCT03069703

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

A Phase 2 study testing PCV13, PPV23 and Rituximab in people with Invasive Pneumococcal Infection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Invasive Pneumococcal Infection
What is being tested?
PCV13, PPV23 and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
1 siteFrance
Study dates
5 Feb 2018to 21 Nov 2021
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 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
  • 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

Who cannot join

  • Participants with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) or other vasculitis
  • Participants with acute infections or chronic active infections at inclusion visit.
  • Documented positive serology result for HIV, HBV (Ag Hbs), HCV at inclusion.
  • 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.
Show all 18Show fewer
  • Participants treated with new other immunosuppressive or immunomodulatory agents within the previous 3 months (including cyclophosphamide, anti-TNF-alpha, intravenous immunoglobulins, abatacept),
  • Participants treated with prednisone dose >10 mg/day for a duration greater than 21 days before inclusion,
  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • 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

Other trials in France

About this study

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

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.

Read the 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.

Being tested
PCV13, PPV23, Rituximab
Keywords
Vaccine, ANCA- associated vasculitides, pneumovax, prevenar, pneumovas
Medical subject headings
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PCV13Biological

    Also called Prevenar

    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)

  • PPV23Biological

    Also called Pneumovax

    one dose of PPV23 at M5

  • RituximabDrug

    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

Study groups in NCT03069703
Study groupRoleWhat they receive
Prime-boost strategyActive comparatora 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)
Receives: Biological: PCV13; Biological: PPV23; Drug: Rituximab
Innovative vaccine strategy 1Experimental2 doses of PCV13 at Day 0 and 2 doses of PCV13 at Day 7, followed by a single dose of PPV23 at M5
Receives: Biological: PCV13; Biological: PPV23; Drug: Rituximab
Innovative vaccine strategy 2Experimental4 doses of PCV13 at Day 0, followed by a single dose of PPV23 at M5
Receives: Biological: PCV13; Biological: PPV23; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 months

Secondary outcomes (2)

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

    proportion of participants with an event; number, nature, grade and time of occurrence.

    Measured: 18 months

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

    proportion of participants with an event; number, nature, grade and time of occurrence.

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2017
  2. Study start5 Feb 2018
  3. Primary completion24 Nov 2020
  4. Study completion21 Nov 2021

Resources

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
Single blind
Who is masked
Outcomes assessor
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03069703
Sponsor's protocol ID
P150964
Other IDs
2016-002888-33, 2016
Acronym
PNEUMOVAS
Status last verified
Oct 2025
First submitted
27 Feb 2017
Last updated
20 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • doi:10.1136/ard.2010.137778

  • doi:10.1136/ard.2008.088302

  • 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.

    PubMed 23851398

  • doi:10.1016/j.vaccine.2011.04.132

  • 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.

    PubMed 25805747

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PCV13, PPV23 and Rituximab in people with Invasive Pneumococcal Infection, run by Assistance Publique - Hôpitaux de Paris 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 8 inclusion and 18 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: finished, as of the sponsor's last update on 20 Nov 2025. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Immunogenicity (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03069703, which also lists 5 linked publications.

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 20 Nov 2025.

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