Natalizumab in Preventing Post-partum Relapses in Multiple Sclerosis

Phase 4

Completed

• Conditions: Multiple Sclerosis
• Interventions: Drug: Natalizumab

• Registration Number: NCT03046251
• Lead Sponsor: State University of New York at Buffalo

Brief Summary

The purpose of this study is to evaluate if monthly natalizumab, initiated after delivery, is effective in preventing postpartum relapses.

Detailed Description

Postpartum patients with a diagnosis of multiple sclerosis (MS) will be given the opportunity to enroll in this study that will evaluate the efficacy of IV natalizumab to prevent postpartum relapses. Natalizumab, administered as 300mg IV q 4 weeks, will be initiated postpartum (0-30 days post-delivery).

Patients who decline natalizumab treatment postpartum will be given the opportunity to enroll in the study in the control group. The control group will have similar inclusion and exclusion criteria as well as scheduled visit and study procedures as the active natalizumab treatment group.

The primary objective of the trial is to assess the efficacy of IV administered natalizumab, monthly for 1 year, in preventing relapses during the postpartum period.

The secondary objectives of the trial are to assess the efficacy of natalizumab in decreasing the risk for disability progression during the postpartum period and to prevent the appearance of new and/or enlarging brain MRI lesions as measured by qualitative MRI analysis.

The tertiary objective is to assess the association of the clinical outcomes with subject evaluations including patient reported outcomes.

Study Timeline

• Study Start: 2015-08
• Study First Submitted: 2017-02-03
• Study First Submitted QC: 2017-02-03
• Study First Posted: 2017-02-08
• Primary Completion: 2023-12
• Study Completion: 2023-12
• Results First Submitted: 2024-09-13
• Results First Submitted QC: 2024-12-30
• Status Verified: 2025-01
• Results First Posted: 2025-01-22
• Last Update Submitted: 2025-01-22
• Last Update Posted: 2025-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

1. Female subjects postpartum, 0-30 days postpartum at the time of informed consent.
2. Diagnosis of relapsing form of MS.
3. Willing to initiating natalizumab and enroll in the TOUCH system.
4. Willing and able to comply with the study procedures for the duration of the trial.
5. Signed informed consent and HIPAA authorization.

Exclusion Criteria

1. Diagnosis of primary progressive MS.
2. Breastfeeding
3. Use of IVIG in Tysabri treated subjects.
4. Significant renal or hepatic impairment (in the opinion of the investigator) or other significant disease (e.g., cognitive impairment) that would compromise adherence and completion of the trial.
5. History of hypersensitivity to previous exposure or presence of antibodies to natalizumab.
6. Any other factor that, in the opinion of the investigator, would make the subject unsuitable for participation in this study.
7. Patients that experience relapses and/or initiated DMT's during pregnancy

The Control group will consist of relapsing MS patients post-delivery who decline natalizumab therapy but open to enroll in the study.

Similar Inclusion and Exclusion criteria as the natalizumab group with the exception of requiring TOUCH enrollment program. The Control group will be allowed to initiate any FDA approved DMT at any time post delivery or remain on no therapy while breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
natalizumab	Natalizumab	Participants in this group are those who opt to receive treatment with natalizumab IV 300mg/day given q 4 weeks for 48 weeks.

Primary Outcome Measures

Name	Time	Method
Relapses Post Partum	52 weeks	The primary endpoint are the relapses during 1 year post-delivery in patients treated with natalizumab. This will be compared to the relapse frequency in the parallel control group.

Secondary Outcome Measures

Name	Time	Method
Expanded Disability Status Scale (EDSS) Worsening	52 weeks	EDSS scores were determined at multiple timepoints, with scores nearest to week 52 selected for analysis. The difference between EDSS scores at baseline and week 52 were calculated, categorizing patients into two groups: stable or worsened. EDSS worsening was defined as a 1.0 increase for baseline scores below 6.0, or a 0.5-point increase for baseline scores of 6.0 or higher.
Difference in Mean Expanded Disability Status Scale (EDSS) Scores Between Persons With MS (pwMS) Treated With Natalizumab Versus Other Disease-modifying Therapies (DMT)	52 weeks	The Expanded Disability Status Scale (EDSS) is a standardized measure of disability progression in multiple sclerosis (MS), ranging from 0 to 10 in 0.5-unit increments, with higher scores indicating greater disability. EDSS scores were determined at multiple timepoints, with scores nearest to week 52 selected for analysis.
Change in MRI	52 weeks	The patients with MS (pwMS) underwent at least two MRI examinations: the first occurring 1-3 months postpartum (before the first post-partum dose of natalizumab) and a follow-up MRI closest to the week 52 visit. For this study, T2-FLAIR and T1-weighted sequences were acquired before and after gadolinium contrast administration. A licensed and experienced neuroradiologist analyzed the MRI scans, determining the number of new or newly enlarging T2 lesions and new T1 contrast-enhancing (GdE) lesions. The identification of new lesions was based on comparisons with pre-pregnancy scans.
Percent of Relapse Free Patients	52 weeks	Percent of relapse free patients between the groups

Trial Locations

Locations (1)

SUNY Buffalo; 🇺🇸 Buffalo, New York, United States