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Secondary Progressive Multiple SclerosisPhase 4AMA-VACCNCT04792567

Exploring the Immune Response to SARS-CoV-2 modRNA Vaccines in Patients With Secondary Progressive Multiple Sclerosis (AMA-VACC)

A Phase 4 study testing BAF312, Baseline disease modifying therapies (DMTs) and BNT162 in people with Secondary Progressive Multiple Sclerosis, run by Novartis Pharmaceuticals at 10 sites in Germany.

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 purpose of this study was to understand whether participants could mount an immune response to SARS-CoV-2 modRNA vaccines administered either during continuous siponimod treatment or during a treatment break versus while on treatment with first-line DMTS or no current MS treatment.. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Secondary Progressive Multiple Sclerosis
What is being tested?
BAF312, Baseline disease modifying therapies (DMTs) and BNT162
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
10 sitesGermany
Study dates
19 Apr 2021to 15 Aug 2022
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Secondary Progressive Multiple Sclerosis (SPMS) diagnosis or with Relapsing Remitting Multiple Sclerosis (RRMS) at risk to develop SPMS (at the discretion of the treating physician)
  • on stable MS treatment (Siponimod, dimethylfumarate, glatirameracetate, interferon, teriflunomode) or no current treatment
  • no recent treatment changes

Who cannot join

  • prior or current COVID-19 disease
  • SARS-CoV-2 antibodies at screening Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Germany10 sites

  • Novartis Investigative Site

    Bogen, 94327

  • Novartis Investigative Site

    Chemnitz, 09117

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Düsseldorf, 40211

  • Novartis Investigative Site

    Mittweida, Saxony, 09648

  • Novartis Investigative Site

    Neuburg an der Donau, 86633

  • Novartis Investigative Site

    Pforzheim, 75172

  • Novartis Investigative Site

    Regensburg, 93059

  • Novartis Investigative Site

    Rülzheim, 76761

  • Novartis Investigative Site

    Ulm, 89073

Other trials in Germany

About this study

Official title: An Open-label Multicenter Study to Assess Response to SARS-CoV-2 modRNA Vaccines in Participants With Secondary Progressive Multiple Sclerosis Treated With Mayzent (Siponimod)

The purpose of this study was to understand whether participants could mount an immune response to SARS-CoV-2 modRNA vaccines administered either during continuous siponimod treatment or during a treatment break versus while on treatment with first-line DMTS or no current MS treatment..

Read the detailed description

This was a three cohort, multicenter, open-label, study of 60 planned (optionally up to 90) multiple sclerosis (MS) patients who were on treatment with siponimod or a first-line disease modifying therapy (DMT) or without MS treatment planning to undergo a SARS-CoV-2 modRNA vaccination as part of clinical routine.

  • The first cohort enrolled participants who did not interrupt their siponimod therapy for the purpose of a SARS-CoV-2 modRNA vaccination.
  • The second cohort enrolled participants who interrupted their siponimod therapy for the purpose of a SARS-CoV-2 modRNA vaccination for approximately 2-3 months
  • The third cohort enrollled participants who received modRNA vaccination while on treatment with the following first-line DMTs (dimethylfumarate, glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine.

The study consists of a screening period, vaccination period and investigational period. During the screening period of up to one month eligibility and SARS-CoV-2 antibodies at baseline were assessed. The 3-4 week vaccination period started with first dose of modRNA vaccine on Day 1 and ended with second dose of modRNA vaccine 3-4 weeks after first dose depending on EU SmPC.

The investigational period lasted 12 months, during which blood samples for primary and secondary endpoint analyses were drawn at 1 week (Visit 1), 1 Month (Visit 2) and 6 months (Visit 3) after completion of vaccination (i.e. second dose of vaccine). 12 months after completion of vaccination a COVID-19 follow-up call was scheduled.

As patients were treated according to clinical routine, the start of treatment was defined as the date the informed consent was signed.

Booster vaccinations were allowed as per local regulations, physician's discretion and as part of clinical routine. This booster may have been any type of SARS-CoV2 vaccine and introduction of a treatment break for the purpose of booster vaccination was at the discretion of the treating physician or patient for all three cohorts. In case of booster vaccinations an additional blood sample was collected 1 month after the booster vaccination (booster Visit).

The planned study duration for each participant was 56-64 weeks, depending on the length of the screening period.

The study investigated the development of functional anti-SARS-CoV-2 antibodies and T-cell titers for six months after the participants' vaccination.

Being tested
BAF312, Baseline disease modifying therapies (DMTs), BNT162, mRNA-1273
Keywords
COVID-19, SARS-CoV-2 mRNA vaccine, Siponimod, Secondary Progressive Multiple Sclerosis, SPMS, adult, MS
Medical subject headings
Multiple Sclerosis, Chronic Progressive, COVID-19

What participants receive

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

  • BAF312Drug

    Also called Siponimod

    taken orally once per day (dose depends on CYP2C9 genotype)

  • Baseline disease modifying therapies (DMTs)Drug

    DMTs: Dimethylfumarate, glatirameracetate, interferon, teriflunomode according to respective SmPC

  • BNT162Biological

    Also called Comirnaty®

    Administerd according to the respective EU SmPC at the discretion of the treating physician independent of AMA-VACC. If suggested by local regulations and performed as part of clinical routine any type of booster/refresher vaccination (e.g. mRNA, vector, peptide) was allowed in this study.

  • mRNA-1273Biological

    Also called Spikevax®

    Administerd according to the respective EU SmPC at the discretion of the treating physician independent of AMA-VACC. If suggested by local regulations and performed as part of clinical routine any type of booster/refresher vaccination (e.g. mRNA, vector, peptide) was allowed in this study

Study groups in NCT04792567
Study groupRoleWhat they receive
Siponimod - continuousExperimentalContinuous treatment with siponimod (oral, daily, dose depending on CYP2C9 genotype: 2mg or 1 mg) during SARS-CoV-2 mRNA vaccination
Receives: Drug: BAF312; Biological: BNT162; Biological: mRNA-1273
Siponimod- interruptedExperimentalSiponimod (oral, daily, dose depending on CYP2C9 genotype: 2mg or 1 mg) with treatment interruption (for approx. 2-3 months) for the purpose of a SARS-CoV-2 mRNA vaccination
Receives: Drug: BAF312; Biological: BNT162; Biological: mRNA-1273
ComparatorActive comparatorBaseline DMTs or no treatment during SARS-CoV-2 mRNA vaccination
Receives: Drug: Baseline disease modifying therapies (DMTs); Biological: BNT162; Biological: mRNA-1273

What is being measured

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

  1. Percentage of Participants Achieving Seroconversion One Week After Receiving Second Vaccine (EAS)

    Participants who had detectable SARS-CoV-2 serum functional antibodies one week after second dose of vaccine.

    Measured: At 1 week after vaccination period (defined as 1 week after second dose of vaccine)

Secondary outcomes (2)

  1. SARS-CoV-2 Functional Antibodies (% Inhibition) by Visits (SAF/EAS)

    Measurement of antibody-mediated blockage (i.e. presence of functional SARS-CoV-2 antibodies) was performed to quantify functional SARS-CoV-2 neutralizing antibodies and was calculated as % inhibition to the in-assay control.

    Measured: Baseline; Week 1, Month 1 and Month 6 after second dose of vaccine; 1 month after booster (up to Month 12 after second dose of vaccine)

  2. Number of Patients Reactive to INFg or IL-2 SARS-CoV-2 by Visit SAF/EAS

    The release of IFNg or IL-2 after stimulation with a SARS-CoV-2/PAN corona peptide-mix measured by enzyme-linked immunosorbent spot (ELIspot) assay from peripheral blood mononuclear cells indicates the presence of SARS-CoV-2 reactive T-cells, i.e. a T-cell response.

    Measured: Baseline; Week 1, Month 1 and Month 6 after second dose of vaccine; 1 month after booster (up to Month 12 after second dose of vaccine)

Timeline

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

  1. First posted11 Mar 2021
  2. Study start19 Apr 2021
  3. Primary completion6 Sep 2021
  4. Study completion15 Aug 2022

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 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04792567
Sponsor's protocol ID
CBAF312ADE03
Other IDs
2020-005752-38
Acronym
AMA-VACC
Status last verified
Jun 2024
First submitted
8 Mar 2021
Last updated
20 Jun 2024
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Publications

  • Ziemssen T, Groth M, Rauser B, Bopp T. Assessing the immune response to SARS-CoV-2 mRNA vaccines in siponimod-treated patients: a nonrandomized controlled clinical trial (AMA-VACC). Ther Adv Neurol Disord. 2022 Nov 8;15:17562864221135305. doi: 10.1177/17562864221135305. eCollection 2022.

    PubMed 36381503

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing BAF312, Baseline disease modifying therapies (DMTs) and BNT162 in people with Secondary Progressive Multiple Sclerosis, run by Novartis Pharmaceuticals at 10 sites in Germany.

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 3 inclusion and 2 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 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants Achieving Seroconversion One Week After Receiving Second Vaccine (EAS) (time frame: At 1 week after vaccination period (defined as 1 week after second dose of vaccine)). 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 NCT04792567, which also lists 1 linked publication.

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 Jun 2024; AzTrials last refreshed its copy on 6 Nov 2026.

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