Kesimpta (Ofatumumab) Pregnancy Registry

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05634967

Collaborator

(none)

725

Enrollment

Location

121.8

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The Kesimpta Pregnancy Registry is an observational, exposure cohort designed study to examine pregnancy and infant outcomes in women and infants who are exposed to Kesimpta (ofatumumab) during pregnancy to treat MS.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis Pregnancy	Other: Kesimpta

Detailed Description

The study is expected to enroll for approximately 7 years and follow the pregnant women and their infant(s) over a maximum of 21 months.

The study will be conducted as two sub-studies leveraging independent ongoing pregnancy registries:

The Organization of Teratology Information Specialists (OTIS) Research Group, University of California, San Diego, USA (referred to as "OTIS") will serve as data source for the Kesimpta-OTIS sub-study;
The German MS and pregnancy registry - Deutschsprachigen Multiple Sklerose und Kinderwunsch Register (DMSKW) at Katholisches Klinikum Bochum gGmbH, St Josef Hospital, Bochum, Germany (referred to as "DMSKW") will serve as data source for the Kesimpta- DMSKW sub-study.

Both registries will independently collect and assess data related to the pregnancy and infant outcomes of interest and provide aggregate data which will be further combined (metaanalyses) by Novartis (referred to as the Sponsor) or a designated contract research organization (CRO).

Study Design

Study Type:

Observational

Anticipated Enrollment :

725 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Post-Authorization Safety Study for Assessment of Pregnancy and Infant Outcomes in Patients Treated With Kesimpta (Ofatumumab) Using OTIS Observational Pregnancy Surveillance Program and DMSKW Registry

Actual Study Start Date :

Jan 5, 2023

Anticipated Primary Completion Date :

Feb 28, 2033

Anticipated Study Completion Date :

Feb 28, 2033

Arms and Interventions

Arm	Intervention/Treatment
Disease-matched cohort (Comparison Group 1) comparison group consisting of women diagnosed with MS who have not used Kesimpta during pregnancy (unexposed disease-matched comparison group).
Healthy cohort (only applicable in the Kesimpta-OTIS sub-study) (Comparison Group 2) healthy women who are not diagnosed with MS or any other autoimmune disease, have not had exposure to a known human teratogen, and have not taken Kesimpta in pregnancy (healthy comparison group). Since the DMSKW register is an MS population specific register that does not collect data on non-MS population, this cohort is only applicable in the Kesimpta-OTIS sub-study.
Kesimpta-exposed cohort women and infants who are exposed to Kesimpta during pregnancy to treat MS.	Other: Kesimpta Prospective non-interventional study. There is no treatment allocation. Patients participating in from the two independent sub-studies, namely the Kesimpta-OTIS sub-study and Kesimpta-DMSKW sub-study, of identical design, conducted in parallel, enrolling pregnant women (MS and non-MS) residing in US or Canada and pregnant women (MS only) from Germany respectively are eligible for enrolling to this study. Other Names: Ofatumumab

Arm

Intervention/Treatment

Disease-matched cohort (Comparison Group 1)

comparison group consisting of women diagnosed with MS who have not used Kesimpta during pregnancy (unexposed disease-matched comparison group).

Healthy cohort (only applicable in the Kesimpta-OTIS sub-study) (Comparison Group 2)

healthy women who are not diagnosed with MS or any other autoimmune disease, have not had exposure to a known human teratogen, and have not taken Kesimpta in pregnancy (healthy comparison group). Since the DMSKW register is an MS population specific register that does not collect data on non-MS population, this cohort is only applicable in the Kesimpta-OTIS sub-study.

Kesimpta-exposed cohort

women and infants who are exposed to Kesimpta during pregnancy to treat MS.

Other: Kesimpta

Prospective non-interventional study. There is no treatment allocation. Patients participating in from the two independent sub-studies, namely the Kesimpta-OTIS sub-study and Kesimpta-DMSKW sub-study, of identical design, conducted in parallel, enrolling pregnant women (MS and non-MS) residing in US or Canada and pregnant women (MS only) from Germany respectively are eligible for enrolling to this study.

Other Names:

Ofatumumab

Outcome Measures

Primary Outcome Measures

Number of participants with major structural defects [Up to 21 months]
Number of participants with major structural defects will be collected

Secondary Outcome Measures

Number of participants with spontaneous abortion/miscarriage [Up to 21 months]
Number of participants with spontaneous abortion/miscarriage will be collected
Number of stillbirth cases [Up to 21 months]
Number of stillbirth cases will be collected
Number of elective termination cases [Up to 21 months]
Number of elective termination cases will be collected
Number of preterm delivery cases [Up to 21 months]
Number of preterm delivery cases will be collected
Number of preeclampsia / eclampsia cases [Up to 21 months]
Number of preeclampsia / eclampsia cases will be collected
Number of cases with pattern of 3 or more minor structural defects [Up to 21 months]
Number of cases with pattern of 3 or more minor structural defects will be collected
Number of participants small for gestational age [Up to 21 months]
Number of participants small for gestational age will be collected
Number of participants with postnatal growth small for age at one year of age [Up to 21 months]
Number of participants with postnatal growth small for age at one year of age will be collected
Developmental performance at approximately one year of age: Michaelis developmental milestones questionnaires [Up to 21 months]
The Michaelis developmental milestones questionnaires will be used to assess the developmental performance in live born infants.
Developmental performance at approximately one year of age: Denver developmental screening test [Up to 21 months]
Denver developmental screening test will be used to assess the developmental performance in live born infants;
Number of serious or opportunistic infections in the first year of life. [Up to 21 months]
Number of serious or opportunistic infections in the first year of life will be collected

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

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: Kesimpta-Exposed Cohort

Pregnant women
Diagnosed with MS, with the indication validated by medical records when possible
Administered Kesimpta for the treatment of MS at any time from 166 days prior to the first day of the LMP, or 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 (OTIS specific), and validated developmental performance questionnaire 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 (OTIS specific), and validated developmental performance questionnaire in live born children

Cohort 3: Healthy Comparison Cohort (Comparison Group 2):Kesimpta-OTIS sub-study specific

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 validated developmental performance questionnaire in live born children

Exclusion Criteria:

Women meeting any of the following criteria will be excluded from the cohort study:

Cohort 1: Kesimpta-Exposed Cohort

Women who have enrolled in the Kesimpta cohort study with a previous pregnancy
Women who have used Kesimpta for an indication other than a currently approved indication
Women with exposure to any of the following medications within 5 half-lives (or pharmacodynamic effect when relevant) prior to conception:

Other anti-CD20 monoclonal antibody: same class as Kesimpta
S1P modulators: same class as Mayzent
Cladribine (Mavenclad): Based on the US label, animal studies indicate that there is positive evidence of teratogenicity for Cladribine
Teriflunomide (Aubagio): The teratogenecity of teriflunomide is unknown and currently under investigation.
New medications (marketed after 2021) 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 diagnostic test(s) that 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)

Administered Kesimpta 166 days before the first day of LMP or anytime during pregnancy
Women with exposure to any of the following medications within 5 half-lives (or pharmacodynamic effect when relevant) of conception:

Anti CD-20 monoclonal antibody
Cladribine (Mavenclad)
S1P modulators
Teriflunomide (Aubagio) New medications (marketed after 2021) indicated for the treatment of MS will be evaluated for inclusion/exclusion criteria as the study progresses.

Women who have enrolled in the Kesimpta cohort or BAF312A2403 Mayzent cohort with a previous pregnancy
Retrospective enrollment after the outcome of pregnancy is known (i.e. the pregnancy has ended prior to enrollment)
Results of diagnostic test(s) that 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): Only applicable to Kesimpta-OTIS sub-study

Administered Kesimpta 166 days before or Mayzent 4 days after the first day of LMP or anytime during pregnancy
Women who have a diagnosis of a MS
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 treated with Mayzent or Kesimpta for non-MS indication
Retrospective enrollment after the outcome of pregnancy is known (i.e. the pregnancy has ended prior to enrollment)
Results of diagnostic test(s) that 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 teratogenic drugs during pregnancy