Assessing pregnancy outcomes in women treated with Mayzent for Multiple Sclerosis

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

This study looks at how pregnancy and baby health are affected in women with Multiple Sclerosis who have taken Mayzent compared to those who haven't and healthy women without MS.

Quick facts

• Study type: Observational
• Enrollment: 867 (estimated)
• Sex: Female
• Sponsor: Novartis (industry)
• Locations: 1 site (La Jolla, California)
• Trial ID: NCT04933552 on ClinicalTrials.gov

What this trial studies

This observational study aims to evaluate pregnancy and infant outcomes in women who have been treated with siponimod (Mayzent) for Multiple Sclerosis. It will compare these outcomes with two groups: women with MS who have not used siponimod and healthy women without MS. Participants will be recruited voluntarily and can withdraw at any time. The study will follow a prospective cohort design to gather data on the effects of siponimod during pregnancy.

Who should consider this trial

Good fit: Ideal candidates include pregnant women diagnosed with Multiple Sclerosis who have been treated with siponimod.

Not a fit: Patients who are not pregnant or those who have not been treated with siponimod for Multiple Sclerosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide valuable insights into the safety of siponimod during pregnancy, helping to inform treatment decisions for pregnant women with Multiple Sclerosis.

How similar studies have performed: Other studies have explored pregnancy outcomes in women with MS, but this specific approach to assessing siponimod exposure is novel.

Eligibility criteria

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

Where this trial is running

La Jolla, California

• Novartis Investigative Site — La Jolla, California, United States (RECRUITING)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions: Multiple Sclerosis, MS, PASS, Post-Authorization Safety Study, Mayzent, Siponimod, Pregnancy