Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, MS, PASS, Post-Authorization Safety Study, Mayzent, Siponimod, Pregnancy
Brief summary
This study will utilize a prospective, observational, exposure cohort design to examine pregnancy and infant outcomes in women and infants who are exposed to siponimod during pregnancy to treat MS.
Detailed description
The prevalence of each outcome in women exposed to siponimod and their infants will be compared to those observed in two unexposed comparator groups: a disease-matched comparison group of women who have not used siponimod during pregnancy but have been diagnosed with MS (disease-matched unexposed comparison group), and a comparison group of healthy women who do not have diagnosis of MS, have not had exposure to a known human teratogen, and have not taken siponimod in pregnancy (healthy comparison group). Pregnant women exposed to siponimod who do not meet the prospective cohort criteria will also be followed as part of an exposure series. All participants will be recruited via voluntary participant registration following informed consent by the pregnant woman for her participation. Participants may withdraw from the study at any time.
Interventions
OTHERSiponimod
Prospective observational cohort study. There is no treatment allocation. Patients administered siponimod, that have started before inclusion of the patient into the study will be enrolled.
Sponsors
Novartis Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
Inclusion criteria
Participants must meet all the criteria listed under the respective cohorts to enroll in that particular cohort of the registry: Cohort 1: Siponimod-Exposed Cohort 1. Pregnant women 2. Diagnosed with MS, with the indication validated by medical records when possible 3. Exposure to siponimod for the treatment of MS, for any number of days, at any dose, and at any time from the 4th day post the first day of LMP prior to conception up to and including the end of pregnancy 4. Agree to the conditions and requirements of the study including the interview schedule, release of medical records, the dysmorphology examination of live born infants, and the Ages and Stages Questionnaire (ASQ) in live born children Cohort 2: Disease-Matched Comparison Cohort (Comparison Group 1) 1. Pregnant women 2. Diagnosed with MS, with the indication validated by medical records when possible 3. May or may not have taken another medication for MS in the current pregnancy 4. Agree to the conditions and requirements of the study including the interview schedule, release of medical records, the dysmorphology examination of live born infants, and the ASQ in live born children Cohort 3: Healthy Comparison Cohort (Comparison Group 2): 1. Pregnant women 2. Agree to the conditions and requirements of the study including the interview schedule, release of medical records, the dysmorphology examination of live born infants, and the ASQ in live born children
Exclusion criteria
Women meeting any of the following criteria will be excluded from the cohort study: Cohort 1: Siponimod-Exposed Cohort 1. Women who have enrolled in the siponimod cohort study with a previous pregnancy 2. Women who have used siponimod for an indication other than a currently approved indication 3. Women with exposure to any of the following medications within 5 half-lives prior to conception: * Cladribine (Mavenclad) * Based on the US label, animal studies indicate that there is positive evidence of teratogenicity for Cladribine * All other S1P modulators including fingolimod (Gilenya), ozanimod, etc. * S1P modulatros are in the same class of drug as siponimod * Teriflunomide (Aubagio) * The teratogenicity of teriflunomide is unknown and currently under investigation * Other anti-CD20 monoclonal antibody: same class as Kesimpta * New medications (marketed after 2020) indicated for the treatment of MS will be evaluated for inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of major structural defects | Up to 10,5 years | A major structural defect is defined as a defect that has either cosmetic or functional significance to the child (e.g., a cleft lip). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of stillbirth | Up to 10,5 years | stillbirth is defined as non-deliberate fetal death anytime in gestation at or after 20 weeks post-LMP. |
| Number of elective termination | Up to 10,5 years | elective termination/abortion is defined as deliberate termination of pregnancy at any time in gestation. Reasons for elective abortions are captured and are classified as due to medical reasons or social reasons. |
| Number of premature delivery | Up to 10,5 years | premature delivery is defined as live birth prior to 37.0 weeks gestation as counted from LMP (or calculated from first-trimester ultrasound-derived due date if last menstrual period uncertain or more than 1 week discrepant). Elective caesarian deliveries or inductions prior to 37.0 completed weeks will be considered separately. |
| Number of preeclampsia / eclampsia | Up to 1 10,5 years | preeclampsia or eclampsia reported by maternal interview with confirmation in medical record or report by medical record only is captured. Preeclampsia is defined as a new onset of hypertension and proteinuria during pregnancy or postpartum. Eclampsia is the new onset of seizures or coma in a pregnant woman with preeclampsia. These seizures are not related to an existing brain condition. |
| Number of spontaneous abortion/miscarriage | Up to 10,5 years | Spontaneous abortion/miscarriage is defined as non-deliberate fetal death which occurs prior to less than 20.0 weeks post-LMP. |
| Small for gestational age | Up to 10,5 years | small for gestational age is defined as birth size (weight, length or head circumference) less than or equal to the 10th centile for sex and gestational age using standard pediatric CDC growth curves for full term or preterm infants (CDC, 2000; Olsen et al., 2010). |
| Postnatal growth small for age at approximately one year of age | Up to 10,5 years | postnatal growth deficiency is defined as postnatal size (weight, length or head circumference) less than or equal to the 10th centile for sex and age using National Center for Health Statistics (NCHS) pediatric growth curves, and adjusted postnatal age for premature infants if the postnatal measurement is obtained at less than one year of age (CDC, 2000). |
| Developmental performance at approximately one year of age | Up to 10,5 years | Screening of Developmental Milestones: one or more domains scored as abnormal on the Ages and Stages Questionnaire completed by the mother when the infant is approximately one year of age will define achievement of developmental milestones. |
| Serious or opportunistic infections in the first year of life | Up to 10,5 years | serious or opportunistic infections are defined as any one or more diagnoses of tuberculosis, x-ray proven pneumonia, neonatal sepsis, meningitis, bacteremia, invasive fungal infection, pneumocysitis, septic arthritis, osteomyelitis, abcess (deep tissue), and infections requiring hospitalization identified in live born infants up to one year of age. |
| Pattern of 3 or more minor structural defects | Up to 10,5 years | A minor structural defect is defined as a defect which has neither cosmetic nor functional significance to the child (e.g., complete 2,3 syndactyly of the toes). Minor structural defects will be identified only through the study dysmorphology examination for live born infants using the study-specific checklist. |
Countries
United States
Contacts
Primary ContactNovartis Pharmaceuticals
Backup ContactDiana Johnson
Outcome results
None listed