Post-Authorization Safety Study for Assessment of Pregnancy Outcomes in Patients Treated With Mayzent

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04933552

Collaborator

(none)

867

Enrollment

Location

125.5

Anticipated Duration (Months)

6.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Other: Siponimod

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

867 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Post-Authorization Safety Study for Assessment of Pregnancy Outcomes in Patients Treated With Mayzent (Siponimod): An OTIS Observational Pregnancy Surveillance Study

Actual Study Start Date :

Dec 15, 2021

Anticipated Primary Completion Date :

May 31, 2032

Anticipated Study Completion Date :

May 31, 2032

Arms and Interventions

Arm	Intervention/Treatment
Siponimod-Exposed Pregnant women with MS exposed to siponimod during pregnancy	Other: Siponimod 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. Other Names: Mayzent
Disease-Matched Comparison Pregnant women with MS not exposed to siponimod during pregnancy
Healthy Comparison Pregnant women who are neither diagnosed with MS nor with any other autoimmune disease, and not exposed to siponimod or any known teratogenic agent during pregnancy

Arm

Intervention/Treatment

Siponimod-Exposed

Pregnant women with MS exposed to siponimod during pregnancy

Other: Siponimod

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.

Other Names:

Mayzent

Disease-Matched Comparison

Pregnant women with MS not exposed to siponimod during pregnancy

Healthy Comparison

Pregnant women who are neither diagnosed with MS nor with any other autoimmune disease, and not exposed to siponimod or any known teratogenic agent during pregnancy

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts 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

Pregnant women
Diagnosed with MS, with the indication validated by medical records when possible
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
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)

Pregnant women
Diagnosed with MS, with the indication validated by medical records when possible
May or may not have taken another medication for MS in the current pregnancy
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):

Pregnant women
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

Women who have enrolled in the siponimod cohort study with a previous pregnancy
Women who have used siponimod for an indication other than a currently approved indication
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
New medications (marketed after 2020) indicated for the treatment of MS will be evaluated for inclusion/exclusion criteria as the study progresses.

Retrospective enrollment after the outcome of pregnancy is known (i.e. the pregnancy has ended prior to enrollment)
Results of a diagnostic test are positive for a major structural defect prior to enrollment. However, women who have had any normal or abnormal prenatal screening or diagnostic test prior to enrollment are eligible as long as the test result does not indicate a major structural defect.

Cohort 2: Disease-Matched Comparison Cohort (Comparison Group 1):

Exposure to siponimod any time from the 4th day post the first day of LMP prior to conception up to and including end of pregnancy
Women with exposure to any of the following medications within 5 half-lives of conception:

Cladribine (Mavenclad)
S1P modulators
Teriflunomide (Aubagio) New medications (marketed after 2020) indicated for the treatment of MS will be evaluated for inclusion/exclusion criteria as the study progresses.

Women who have enrolled in the siponimod cohort study with a previous pregnancy
Retrospective enrollment after the outcome of pregnancy is known (i.e. the pregnancy has ended prior to enrollment)
Results of a diagnostic test are positive for a major structural defect prior to enrollment. However, women who have had any normal or abnormal prenatal screening or diagnostic test prior to enrollment are eligible as long as the test result does not indicate a major structural defect.

Cohort 3: Healthy Comparison Cohort (Comparison Group 2):

Exposure to siponimod any time from the 4th days post first day of LMP prior to conception to and including end of pregnancy
Women who have a diagnosis of a MS or a siponimod approved indication
Women who have a current diagnosis of any autoimmune disease
Women who have first contact with the project after prenatal diagnosis of any major structural defect
Women who have enrolled in the siponimod cohort study with a previous pregnancy
Retrospective enrollment after the outcome of pregnancy is known (i.e. the pregnancy has ended prior to enrollment)
Results of a diagnostic test are positive for a major structural defect prior to enrollment. However, women who have had any normal or abnormal prenatal screening or diagnostic test prior to enrollment are eligible as long as the test result does not indicate a major structural defect.
Women exposed to a known human teratogen during pregnancy as confirmed by the OTIS Research Center