Natalizumab in Preventing Post-partum Relapses in Multiple Sclerosis (NAPPREMS)

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

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Natalizumab

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14203
      • SUNY Buffalo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: natalizumab; Participants in this group are those who opt to receive treatment with natalizumab IV 300mg/day given q 4 weeks for 48 weeks.	Drug: Natalizumab
No Intervention: Control; Participants in this group may initiate any FDA approved DMT at any time post delivery or remain on no therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapses Post Partum	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.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expanded Disability Status Scale (EDSS) Worsening	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.	52 weeks
Difference in Mean Expanded Disability Status Scale (EDSS) Scores Between Persons With MS (pwMS) Treated With Natalizumab Versus Other Disease-modifying Therapies (DMT)	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.	52 weeks
Change in MRI	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.	52 weeks
Percent of Relapse Free Patients	Percent of relapse free patients between the groups	52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in QoL Measures	The study participants completed multiple patient-reported outcome (PRO) questionnaires: the Multiple Sclerosis Impact Scale-29 (MSIS-29) and the Fatigue Scale for Motor and Cognitive Function (FSMC). The MSIS-29 is a psychometrically validated 29-item measure widely used in MS treatment trials, consisting of two domains: a 20-item physical impact subscale and a 9-item psychological impact subscale. The FSMC is a 20-item scale designed to assess fatigue in MS patients, with 10 items each for cognitive and motor fatigue. Both scales have proven to be valuable tools in assessing the impact of MS on patients' daily lives and are frequently used in clinical trials and research settings.	52 weeks
Proportion of Postpartum MS Patients With Disability Progression Comparing Those Who Used a Disease Modifying Therapy (DMT) After Delivery vs Those Who Did Not Re-start a DMT After Delivery.	To evaluate the impact of postpartum DMT use on disability progression, we compared the proportion of patients experiencing confirmed EDSS worsening at 52 weeks between those who restarted DMT after delivery and those who did not. Confirmed EDSS worsening was defined as an increase of ≥1.0 point from baseline for patients with baseline EDSS <6.0, or ≥0.5 points for patients with baseline EDSS ≥6.0, sustained for at least 12 weeks.	52 weeks
Difference in EDSS Scores Between Patients With MS (pwMS) Who Used a Disease Modifying Therapy (DMT) After Delivery vs Those Who Did Not Re-start a DMT After Delivery.	To evaluate the impact of postpartum DMT use on disability progression, we compared the mean EDSS scores (a standardized measure of MS disability ranging from 0-10) at 52 weeks between patients who restarted DMT after delivery and those who did not.	52 weeks

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Investigators: Principal Investigator: Bianca Weinstock-Guttman, MD, SUNY Buffalo

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: February 3, 2017
• First Submitted That Met QC Criteria: February 3, 2017
• First Posted (Estimated): February 8, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 22, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Immunologic Factors; Physiological Effects of Drugs; Natalizumab
• Other Study ID Numbers: US-TYS-14-10720

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes