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) (AMA-VACC)

• Register: EUCTR
• Last refreshed on: 26 October 2021
• Main ID: EUCTR2020-005752-38-DE
• Date of registration: 19/01/2021
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public 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) (AMA-VACC)
• Scientific 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) (AMA-VACC)
• Date of first enrolment: 18/03/2021
• Target sample size: 60
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-005752-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: max recommended dose at the discretion of the investigator (routinely used first line MS treatments); Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Germany

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent must be obtained prior to participation in the study.
2. One of the following MS treatments as part of clinical routine:
a. Cohort 1: Siponimod treatment according to EU SmPC without interrupting daily dosing for the purpose of vaccination with SARS-CoV-2 modRNA
b. Cohort 2: Siponimod treatment according to EU SmPC interrupting daily dosing for the purpose of vaccination with SARS-CoV-2 modRNA
c. Cohort 3: Dimethylfumarate, glatirameracetate, interferon, teriflunomode as per respective EU SmPC or no current treatment with diagnosis of SPMS or with RRMS at risk to develop SPMS (at the discretion of the treating physician)
3. Planning to receive a SARS-CoV-2 modRNA vaccination as part of clinical routine
4. No change regarding DMT within 4 weeks prior to inclusion to AMA-VACC, i.e. stable on current DMT according to dosing within label, no interruption, start or withdrawal of DMT in this period of time and no planned switch of DMT within following 2 months
5. Patients willing and eligible to receive a modRNA vaccine against COVID-19 as part of clinical routine

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1. History of COVID-19
2. SARS-CoV-2 antibodies at screening
3. Patients likely not being able or willing to complete the study
4. Use of other investigational drugs within 5 half-lives of enrollment/initiation of study treatment (e.g. small molecules) or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer
5. Patients with any medical or psychological condition that, in the investigators opinion, renders the patient unable to understand the nature, scope, and possible consequences of the study and who are therefore not able to comply with the requirements of the study and capable of giving informed consent
6. No person directly associated with the administration of the study is allowed to participate as a study subject
7. No family member of the investigational study staff is allowed to participate in this study
8. Known or suspected clinically relevant allergy, intolerance or hypersensitivity to peanuts, soya (only cohort 1 and 2) or to any of the study treatments designated for the individual subject (DMTs or mRNA vaccines) or drugs of similar chemical classes (active substance or excipients)
9. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 10 days of study treatment after stopping medication.
10. For cohort 3: patients with contraindications for their current MS medication according to the respective EU SmPC


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

secondary progressive multiple sclerosis (SPMS)

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Mayzent 2 mg Filmtabletten
Product Name: Mayzent 2 mg Filmtabletten
Product Code: BAF312A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SIPONIMOD
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
Other descriptive name: Siponimod
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: Mayzent 0,25 mg Filmtabletten
Product Name: Mayzent 0,25 mg Filmtabletten
Product Code: BAF312A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SIPONIMOD
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
Other descriptive name: Siponimod
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Trade Name: Spikevax
Pharmaceutical Form: Dispersion for injection
INN or Proposed INN: COVID-19 mRNA Vaccine (nucleoside modified)
Other descriptive name: COVID-19 mRNA vaccine Moderna (CX-024414)
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DIMETHYL FUMARATE
CAS Number: 624-49-7
Other descriptive name: DIMETHYL FUMARATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 240-

Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TERIFLUNOMIDE
CAS Number: 108605-62-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 14-

Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: GLATIRAMER ACETATE
CAS Number: 147245-92-9
Other descriptive name: GLATIRAMER ACETATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: RECOMBINANT INTERFERON BE

Primary Outcome(s)

Main Objective: To estimate the proportion of those achieving seroconversion (i.e. having SARS-CoV-2 serum functional antibodies) after receiving a modRNA vaccine in participants treated concomitantly with siponimod and siponimod treatment break.

Primary end point(s): Proportion of participants achieving seroconversion as defined by detection of SARS-CoV-2 serum functional antibodies one week after second dose of vaccine in participants treated concomitantly with siponimod and siponimod treatment break (yes/no)

Timepoint(s) of evaluation of this end point: 1 week after second dose of vaccine in participants treated concomitantly with siponimod and siponimod treatment break

Secondary Objective: • Describing SARS-CoV-2 serum functional antibody levels in participants treated concomitantly with siponimod versus siponimod treatment break versus first-line DMTs and in patients currently not on a DMT
• Describing the T cell response to modRNA vaccines in participants treated concomitantly with siponimod versus siponimod treatment break versus first-line DMTs and in patients currently not on a DMT
• Describing safety, incl. AEs related to discontinuation and new onset of siponimod treatment and patients developing COVID-19

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1 week, 1 month and six months after second dose of vaccine plus one month after booster vaccination

Secondary end point(s): • SARS-CoV-2 serum functional antibody levels one week, one month and six months after second dose of vaccine and additionally one month after an optional booster vaccination in participants treated concomitantly with siponimod versus siponimod treatment break versus first-line DMTs and in patients currently not on a DMT
• SARS-CoV-2 specific T-cell levels one week, one month and six months after second dose of vaccine and additionally one month after an optional booster vaccination in participants treated concomitantly with siponimod versus siponimod treatment break versus first-line DMTs and in patients currently not on a DMT measured by e.g. enzyme-linked immunosorbent spot (ELIspot) assay from peripheral blood mononuclear cells that were stimulated with SARS-CoV-2 peptide mix
• AEs, SAEs, incl. patients with clinical confirmed COVID-19, events leading to discontinuation in participants treated concomitantly with siponimod versus siponimod treatment break versus first-line DMTs and in patients currently not on a DMT

Secondary ID(s)

CBAF312ADE03

Source(s) of Monetary Support

Novartis Pharma GmbH

Ethics review

Status: Approved
Approval date: 18/03/2021
Contact: