A Phase 4 interventional study of Two-dose M0-M2 vaccination schedule and Two-dose M0-M6 vaccination schedule in Vaccine, Varicella-zoster Virus and Multiple Sclerosis, sponsored by University Hospital, Toulouse. Not yet recruiting at 24 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-14.
Sponsored by University Hospital, Toulouse · Phase 4, Interventional, and Treatment
Immunocompromised individuals, such as patients with multiple sclerosis (MS) or diseases of the neuromyelitis optica spectrum (NMOSD) treated with an anti-CD20 monoclonal antibody, present an increased risk of shingles. The immunogenicity - and therefore the clinical effectiveness - of the recombinant vaccine against the varicella zoster virus based on glycoprotein E, recently recommended according to two-dose schedule two months apart in immunocompromised patients aged ≥ 18 years, could be significantly decreased when administered one month before and one month after the infusion of anti-CD20.
We hypothesize that, in patients with MS or NMOSD treated with anti-CD20 administered every six months, a two-dose M0-M6 vaccination schedule consisting of deferring the second dose six months after the first infusion, that is, five months after the anti-CD20 infusion, could improve vaccine immunogenicity and, consequently, the effectiveness of the vaccine.
Shingles, caused by reactivation of varicella zoster virus (VZV), is a common condition in immunocompromised people. Its prevention, which has long remained a medical need unmet among these patients, was improved thanks to the availability of the recombinant glycoprotein-based VZV vaccine E (gE). Based on demonstrated clinical efficacy and safety profile in the general population as well as in immunocompromised patients, this vaccine is recommended in France according to a two-person schedule doses spaced two months apart in immunocompromised patients aged ≥ 18 years. However, further studies are needed in order to optimize vaccination strategies according to the different types of immunosuppression.
Patients with MS or NMOSD, who are at increased risk of herpes zoster, are extensively treated with anti-CD20 monoclonal antibodies, which are known to significantly alter immune responses to vaccines, in particular when vaccination is carried out early after the infusion of anti-CD20.
We hypothesize that in patients with MS or NMOSD treated with anti-CD20 administered every six months, a two-dose M0-M6 vaccination schedule, consisting of deferring the second dose to six months after the first, that is, five months after the anti-CD20 infusion, could improve vaccine immunogenicity and, consequently, the effectiveness of the vaccine.
In this phase IV randomized, controlled, open-label, parallel-group trial, we will compare, within a homogeneous population of patients with MS or NMOSD receiving antiCD20, the humoral response induced by a two-dose vaccination schedule administered at 2 months (M0-M2, "2-month" or standard group) or 6 months (M0-M6, "6-month" or experimental group). After the screening and inclusion phase, patients randomized to the M0-M2 (standard) and M0-M6 (experimental) groups will receive a first dose of recombinant herpes zoster vaccine (RZV) one month before the next scheduled infusion of anti-CD20 monoclonal antibodies (M1). The second dose of RZV will be given at either 2 months ("2-month group", M2) or 6 months ("6-month group", M6). Patients will receive their usual anti-CD20 monoclonal antibody infusions at the appropriate time M1, M7 and M13. The primary outcome will be evaluated one month after the second vaccine dose (M3 for the "2 months" group and M7 for the "6 months" group). The kinetics, intensity, and persistence of humoral and cellular immune responses, as well as safety, will be analyzed as criteria for secondary judgments during the scheduled follow-up visits until M13.
180 studies on the registry are indexed under Chickenpox; 28 are open to participants now.
This study's planned enrollment of 160 is below the median of 475 across 149 interventional studies indexed under Chickenpox.
Browse Chickenpox studies →University Hospital, Toulouse is the lead sponsor of 807 studies on the registry; 209 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Hypersensitivity to the active substance or to any of the excipients Severe, active infections Severe immunodeficiency Severe heart failure or severe uncontrolled heart disease Known progressive
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients will receive the standard vaccination schedule in two doses in 2 months.
Biological: Two-dose M0-M2 vaccination schedule
Patients will receive a vaccination schedule in two doses in 6 months.
Biological: Two-dose M0-M6 vaccination schedule
Patients randomized to the "2 months" vaccination group will receive their first dose of RZV vaccine one month before the next scheduled infusion anti-CD20 monoclonal antibody (M0 corresponding to the visit during the first dose of vaccine, M1 at the time of scheduled anti-CD20 infusion). The second dose of RZV vaccine will be administered 2 months later. Patients will receive their regular anti-CD20 infusions at times M1, M7, and M13.
Patients randomized to the "6 months" vaccination group will receive their first dose of RZV vaccine one month before the next scheduled infusion anti-CD20 monoclonal antibody (M0 corresponding to the visit during the first dose of vaccine, M1 at the time of scheduled anti-CD20 infusion). The second dose of RZV vaccine will be administered 6 months later. Patients will receive their regular anti-CD20 infusions at times M1, M7, and M13.
Humoral vaccine response rate for IgG anti-VZV gE response
It will be defined as the proportion of patients with at least a 4-fold increase in anti-VZV gE antibody titers (measured by ELISA) at 1 month after the 2nd vaccine dose compared to baseline (M0), or seroconversion for those who were seronegative at M0.
Time frame: 3 months for the " 2 months " group and 7 months for the " 6 months " group
The humoral response in terms of Geometric Mean Titer (GMT) at 1 month after the 2nd vaccine dose.
It will be assessed by the ratio (M0-M6 versus M0-M2 groups) of the adjusted Geometric Mean Titer (GMT) of anti-VZV gE IgG at 1 month after the 2nd vaccine dose. The adjusted GMT will correspond to the GMT at 1 month after the 2nd vaccine dose conditionally to the means of the log transformed GMT before vaccination at baseline (M0) calculated across the treatment groups.
Time frame: 3 months for the " 2 months " group and 7 months for the " 6 months " group
Composite criteria of the humoral response up to M13
The kinetics, intensity and persistance will be assessed by the Geometric Mean Titer (GMT) of anti-VZV gE IgG measured at baseline (M0) and up to M13: before the 2nd vaccine dose, 1 month after the 2nd vaccine dose, and prior to the next anti CD20 infusions at M7 and M13.
Time frame: 13 months
Composite criteria of the cellular response at 1 month after the 2nd vaccine dose
It will be assessed by the cellular vaccine response rate for gE-specific CD4\[AIM+\] T response measured 1 month after the 2nd vaccine dose. The cellular VRR is defined as the proportion of patients with a proportion of gE-specific CD4\[AIM+\] T cells at least 2 times above the cutoff after vaccination. The proportion of gE-specific CD4\[AIM+\] T cells among CD4 T cells is defined by the proportion of CD4 T cells expressing at least one Activation-Induced Marker (AIM), as detected by flow cytometry, following in vitro stimulation with a peptide pool covering the entire ectodomain of gE. The AIM include CD69, CD25, OX40, CD40L, and CD137. We will determine the cut-off of gE-specific CD4\[AIM+\] T cells by assessing cellular immune responses across a range of non-vaccinated, healthy individuals.
Time frame: 3 months for the " 2 months " group and 7 months for the " 6 months " group
Composite criteria of the cellular response at M13
The kinetics, intensity and persistance of the cellular response up to M13 will be assessed by the proportion of gE-specific CD4\[AIM+\] T cells among CD4 T cells measured at baseline (M0) and up to M13 : before the 2nd vaccine dose, 1 month after the 2nd vaccine dose, and prior to the next anti-CD20 infusions at M7 and M13.
Time frame: 13 months
The vaccine safety
The safety will be assessed by the adverse events including serious adverse events collected during the study.
Time frame: from M0 to month 13
Composite criteria of the predicted humoral response at M20
Predicted humoral vaccine response rate will be assessed by the predicted humoral vaccine response rates at M20 of the M0-M6 RZV vaccine schedule ("6 months" group) and the M0-M2 RZV vaccine schedule ("2 months" group). Anti-VZV gE IgG at M20 will be assessed by the adjusted Geometric Mean Titers of anti-VZV gE IgG at M20 of the M0-M6 RZV vaccine schedule ("6 months" group) and the M0-M2 RZV vaccine schedule ("2 months" group).
Time frame: 20 months
The overall predicted humoral exposure from M0 to M20
It will be assessed by the areas under the curve (AUC) of anti-VZV gE IgG titers between M0 and M20 of the M0-M6 RZV vaccine schedule ("6 months" group) and the M0-M2 RZV vaccine schedule ("2 months" group).
Time frame: 20 months
The predicted cellular response at M20
It will be assessed by the predicted cellular vaccine rate response proportions of gE specific CD4\[AIM+\] T cells among CD4 T cells of the M0-M6 RZV vaccine schedule ("6 months" group) and the M0-M2 RZV vaccine schedule ("2 months" group).
Time frame: 20 months
The overall predicted cellular exposure from M0 to M20
It will be assessed by the areas under the curve (AUC) of gE-specific CD4\[AIM+\] T cells among CD4 T cells between M0 and M20 of the M0-M6 RZV vaccine schedule ("6 months" group) and the M0-M2 RZV vaccine schedule ("2 months" group).
Time frame: 20 months
Composite criteria of the associated factors with early and persistent, humoral and cellular vaccine responses
The factors which will be studied are : age, sex, number of prior anti-CD20 infusions, type of latest DMT before anti-CD20 therapy, albumin and gammaglobulin levels, Ig G levels, leukocyte counts, T and B cell immunophenotyping, and immune exhaustion and immunosenescence markers throughout the study.
Time frame: 20 months
The correlation between the titers of anti-VZV gE IgG by ELISA and the titers of total IgG anti-VZV by the commercial Diasorin serological test.
It will be assessed by the correlation between ELISA gE titer and the total anti-VZV glycoproteins IgG measured by the Liaison XL® Diasorin serological test.
Time frame: 20 months
Plan to share: Undecided
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Start is estimated for Oct 2026; primary completion for Jun 2030, 44 months later.
Of 14 phase 4 interventional studies under Chickenpox, half reached primary completion within 4 months of starting (the median), counting those still running; a quarter within 2 and three quarters within 22. This study's planned 44 months is above that.
How these figures are worked out, and which studies are left out of them.
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