Safety of Exposure to Natalizumab During Pregnancy

Multiple Sclerosis Clinical Trial

— BABYZUMAB-2  

Official title:

Safety of Exposure to Natalizumab During Pregnancy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05209815
• Other study ID #: CHUBX 2020/65
• Status: Completed
• Start date: June 20, 2022
• Est. completion date: December 22, 2023

Study information

• Verified date: January 2024
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Multiple sclerosis (MS) preferentially affects young adults with a female predominance. MS is not associated with an increased risk of complications or abnormal pregnancy outcomes. Nevertheless, disease-modifying therapies can have a teratogenic effect. Discussions about discontinuation should be made with a view to or upon discovery of pregnancy, taking into account the risk of untreated relapses and the risk of toxicity to the fetus.

Natalizumab (NTZ) is a humanized anti-alpha4-integrin monoclonal antibody used as a treatment for highly active relapsing-remitting MS (RRMS). When it is stopped, there is frequent reactivation of the disease with possible relapses and a rebound effect could occur. At present, depending on the center, attitudes of neurologist may vary and 3 main scenarios can be observed: Pregnancy and postpartum under NTZ (group1), Pregnancy partially under NTZ (with or without immunomodulator (IM) supplementation, group 2), or NTZ stopped before pregnancy (with or without IM supplementation, group3).

The first part of the BABYZUMAB study, a retrospective study of Natalizumab exposure during pregnancy, analysed the comparison the clinical activity of the disease (annualized relapse rate) according to these 3 scenarios of NTZ treatment The investigators analyzed the annual relapse rate (ARR) during a two-year period (9 months before and 15 months after the beginning of the pregnancy) in 117 patients identified in the OFSEP database. The investigators showed that the risk of relapses was four times higher in Group 2 versus Group 1 (p=0,014) and six times higher in Group 3 versus Group 1 (p=0,001).

In the literature, there are few studies of newborns from NTZ-exposed pregnancies. No specific pattern of birth defects has been found, but mild to moderate transient thrombocytopenia and anemia have been reported in infants born to NTZ-exposed mothers in the third trimester of pregnancy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: December 22, 2023
• Est. primary completion date: December 22, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age greater than 18 years at the index date (date of pregnancy onset) of data collection,

• RRMS according to McDonald's 2017 criteria (Thompson et al., 2018)

• Affiliated person or beneficiary of a social security scheme.

• followed up at one of the participating centers (OFSEP centers)

• NTZ exposure during pregnancy according to 3 pre-defined sub-groups: continuation of NTZ throughout pregnancy and postpartum (Group 1), exposure during the first trimester (Group 2) exposure during the first and the second trimester (Group 3).

• Participants capable of expressing non objection

• French-speaking, without comprehension disorders

Exclusion Criteria:

• Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent)

Related Conditions & MeSH terms

• Multiple Sclerosis

Intervention

Behavioral:
• Questionnaire
Questionnaire

Locations

Country	Name	City	State
France	CHRU de Besançon - service de neurologie	Besançon
France	CHU de Bordeaux - service de neurologie	Bordeaux
France	HCL - service de neurologie	Bron
France	CH Sud Francilien - service de neurologie	Corbeil-Essonnes
France	AP-HP - Hôpital de Créteil - service de neurologie	Créteil
France	CHU de Dijon-Bourgogne	Dijon
France	CHU de Grenoble-Alpes	La Tronche
France	CHRU de Lille - service de neurologie	Lille
France	CHU de Limoges - service de neurologie	Limoges
France	AP-HM - service de neurologie	Marseille
France	CHU de Montpellier - service de neurologie	Montpellier
France	CHRU de Nancy - service de neurologie	Nancy
France	CHU de Nantes - service de neurologie	Nantes
France	CHU de Nice - service de neurologie	Nice
France	CHU de Nîmes - service de neurologie	Nîmes
France	AP-HP - Hôpital La Pitié Salpétrière - service de neurologie	Paris
France	AP-HP - Hôpital Saint-Antoine - service de neurologie	Paris
France	Fondation Rothschild - service de neurologie	Paris
France	CHU de Poitiers - service de neurologie	Poitiers
France	CHU de Rennes - service de neurologie	Rennes
France	CHU de Rouen - service de neurologie	Rouen
France	CH de Saint-Denis - service de neurologie	Saint-Denis
France	CHU d'Amiens - service de neurologie	Salouël
France	CHRU de Strasbourg - service de neurologie	Strasbourg
France	CHU de Toulouse - service de neurologie	Toulouse
France	CHU de Tours - service de neurologie	Tours
Martinique	CHU de Fort de France - service de neurologie	Fort-de-France

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Biogen

Countries where clinical trial is conducted

France,  Martinique, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who presented serious adverse events (SAE) during their pregnancy		At baseline (Day 0)
Secondary	Proportion of patients who presented pregnancy complications		At baseline (day 0)
Secondary	Proportion of patients who presented delivery complications		At baseline (day 0)
Secondary	Proportion of patients who presented postpartum AEs of interest		At baseline (day 0)
Secondary	Proportion of viable children at birth		At baseline (day 0)
Secondary	Average weight at birth		At baseline (day 0)
Secondary	apgar score at birth		At baseline (day 0)
Secondary	Number of child AEs of interest (haematological, infectious, malformations) at birth		At baseline (day 0)
Secondary	Number of child AEs of interest (haematological, infectious, malformations) two years after birth		At baseline (day 0)