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

Secondary Progressive Multiple Sclerosis Clinical Trial

— AMA-VACC  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04792567
• Other study ID #: CBAF312ADE03
• Secondary ID: 2020-005752-38
• Status: Completed
• Phase: Phase 4
• Start date: April 19, 2021
• Est. completion date: August 15, 2022

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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..

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: August 15, 2022
• Est. primary completion date: September 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Neoplasm Metastasis
• Sclerosis
• Secondary Progressive Multiple Sclerosis

Intervention

Drug:
• BAF312
taken orally once per day (dose depends on CYP2C9 genotype)
• Baseline disease modifying therapies (DMTs)
DMTs: Dimethylfumarate, glatirameracetate, interferon, teriflunomode according to respective SmPC

Biological:
• BNT162
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-1273
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

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Bogen
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Düsseldorf
Germany	Novartis Investigative Site	Mittweida	Sachsen
Germany	Novartis Investigative Site	Neuburg an der Donau
Germany	Novartis Investigative Site	Pforzheim
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Ruelzheim
Germany	Novartis Investigative Site	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 1 week after vaccination period (defined as 1 week after second dose of vaccine)
Secondary	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.	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)
Secondary	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.	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)

External Links

•   Patient Lay Trial Summary