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

Novartis

Status: Enrolling

Conditions: Multiple Sclerosis

Treatments: Other: Siponimod

Study type: Observational

Funder types: Industry

Identifiers

NCT04933552

CBAF312A2403

Details and patient eligibility

About

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.

Full 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.

Enrollment: 867 estimated patients

Sex: Female

Volunteers: Accepts Healthy Volunteers

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/exclusion criteria as the study progresses.

4. Retrospective enrollment after the outcome of pregnancy is known (i.e. the pregnancy has ended prior to enrollment)

5. 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):

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

2. Women with exposure to any of the following medications within 5 half-lives of conception:

   • Cladribine (Mavenclad)
   • S1P modulators
   • Teriflunomide (Aubagio)
   • Anti CD-20 monoclonal antibody New medications (marketed after 2020) indicated for the treatment of MS will be evaluated for inclusion/exclusion criteria as the study progresses.

3. Women who have enrolled in the siponimod cohort or OMB157G2403 Kesimpta cohort with a previous pregnancy

4. Retrospective enrollment after the outcome of pregnancy is known (i.e. the pregnancy has ended prior to enrollment)

5. 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):

1. Exposure to Kesimpta 166 days before or to siponimod any time from the 4th day post first day of LMP prior to conception to and including end of pregnancy
2. Women who have a diagnosis of a MS or a siponimod approved indication
3. Women who have a current diagnosis of any autoimmune disease
4. Women who have first contact with the project after prenatal diagnosis of any major structural defect
5. Women who have enrolled in the siponimod cohort or Kesimpta cohort study with a previous pregnancy
6. Women treated with Mayzent or Kesimpta for non-MS indication
7. Retrospective enrollment after the outcome of pregnancy is known (i.e. the pregnancy has ended prior to enrollment)
8. 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.
9. Women exposed to a known human teratogen during pregnancy as confirmed by the OTIS Research Center

Trial design

867 participants in 3 patient groups

Siponimod-Exposed

Description:

Pregnant women with MS exposed to siponimod during pregnancy

Treatment:

Other: Siponimod

Disease-Matched Comparison

Description:

Pregnant women with MS not exposed to siponimod during pregnancy

Healthy Comparison

Description:

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