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The purpose of this study is to evaluate if monthly natalizumab, initiated after delivery, is effective in preventing postpartum relapses.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| natalizumab | Other | Participants in this group are those who opt to receive treatment with natalizumab IV 300mg/day given q 4 weeks for 48 weeks. |
|
| Control | No Intervention | Participants in this group may initiate any FDA approved DMT at any time post delivery or remain on no therapy. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Natalizumab | Drug |
|
| 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 |
| 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. |
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Bianca Weinstock-Guttman, MD | SUNY Buffalo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| SUNY Buffalo | Buffalo | New York | 14203 | United States |
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Post-delivery patients enrolled and followed for 52 weeks. Study had difficulty in enrollment locally (Buffalo).
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| ID | Title | Description |
|---|---|---|
| FG000 | Natalizumab | Participants in this group are those who opt to receive treatment with natalizumab IV 300mg/day given q 4 weeks for 48 weeks. Natalizumab |
| FG001 | Control | Participants in this group may initiate any FDA approved DMT at any time post delivery or remain on no therapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Only 30 patients enrolled
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| ID | Title | Description |
|---|---|---|
| BG000 | Natalizumab | Participants in this group are those who opt to receive treatment with natalizumab IV 300mg/day given q 4 weeks for 48 weeks. Natalizumab |
| BG001 | Control | Participants in this group may initiate any FDA approved DMT at any time post delivery or remain on no therapy. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Two of the 4 natalizumab users reported post-partum relapses, compared to 7 out of the 24 who were not using natalizumab post-partum. | Posted | Count of Participants | Participants | 52 weeks |
|
52 weeks
Serious side effects Infections Jaundice Anemia Allergy or infection in the brain Acute hypersensitivity reactions Cholelithiasis
Common side effects Headache Fatigue Urinary tract infection Joint pain Lung infection Depression Pain in arms or legs Diarrhea Vaginitis Rash Relapse not requiring hospitalization
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Natalizumab | Participants in this group are those who opt to receive treatment with natalizumab IV 300mg/day given q 4 weeks for 48 weeks. Natalizumab |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| MS relapse | Nervous system disorders | Non-systematic Assessment | MS relapse not requiring hospitalization |
The study's nature required long waiting periods for pregnancies, and not all pregnant pwMS were open to enrollment. The demands of early motherhood led to significant drop-out rates over the four follow-up visits. Many patients opted out of starting natalizumab post-delivery as initially intended. These factors, combined with the COVID-19 pandemic, which significantly impacted research participation, resulted in a small sample size and diminishing cases throughout the follow-up period.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Bianca Weinstock-Guttman | Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY, USA. | 716-829-4415 | bw8@buffalo.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 15, 2019 | Sep 10, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 2, 2021 | Sep 10, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| ID | Term |
|---|---|
| D000069442 | Natalizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| 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 |
| 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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Expanded Disability Status Scale (EDSS) | The Expanded Disability Status Scale (EDSS) is a measure used to assess disability levels in individuals with multiple sclerosis. It ranges from 0 (no disability) to 10 (death due to MS). Scores from 1.0 to 4.5 indicate patients with significant ambulatory abilities, while scores from 5.0 to 9.5 reflect progressive loss of mobility. | Mean | Standard Deviation | units on a scale |
|
|
|
| Secondary | 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. | Number of patients who worsened in EDSS scores comparing baseline visit to visit closest to 52 weeks. | Posted | Count of Participants | Participants | 52 weeks |
|
|
|
| Secondary | 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. | Persons with MS with available EDSS scores comparing the visit closest to 52 weeks between those treated with natalizumab vs other DMTs. | Posted | Mean | Standard Deviation | score on a scale | 52 weeks |
|
|
|
| Secondary | 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. | Patients with MS (pwMS) with available MRI data | Posted | Count of Participants | Participants | 52 weeks |
|
|
|
| Secondary | Percent of Relapse Free Patients | Percent of relapse free patients between the groups | Relapse free at 52 weeks | Posted | Count of Participants | Participants | 52 weeks |
|
|
|
| Other Pre-specified | 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. | Worsening of MSIS physical, mental, or FSMC worsening comparing baseline to week 52. | Posted | Count of Participants | Participants | 52 weeks |
|
|
|
| Other Pre-specified | 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. | Persons with MS (pwMS) who participated in this study. | Posted | Count of Participants | Participants | 52 weeks |
|
|
|
| Other Pre-specified | 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. | Persons with MS (pwMS) who participated in this study. | Posted | Mean | Standard Deviation | score on a scale | 52 weeks |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 2 |
| 4 |
| EG001 | Control | Participants in this group may initiate any FDA approved DMT at any time post delivery or remain on no therapy. | 0 | 26 | 0 | 26 | 7 | 26 |
|
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| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| NEW GdE lesions |
|
|
| FSMC Worsening |
|