Multiple Sclerosis
Conditions
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.
Interventions
DRUGNatalizumab
Sponsors
State University of New York at Buffalo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. | 52 weeks | 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. |
| 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. | 52 weeks | 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. |
| Change in QoL Measures | 52 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Post-delivery patients enrolled and followed for 52 weeks. Study had difficulty in enrollment locally (Buffalo).
Participants by arm
| Arm | Count |
|---|---|
| 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 | 4 |
| Control Participants in this group may initiate any FDA approved DMT at any time post delivery or remain on no therapy. | 26 |
| Total | 30 |
Baseline characteristics
| Characteristic | Natalizumab | Control | Total |
|---|---|---|---|
| Age, Continuous | 35.3 years STANDARD_DEVIATION 4.3 | 31.8 years STANDARD_DEVIATION 5.6 | 32.3 years STANDARD_DEVIATION 5.5 |
| Expanded Disability Status Scale (EDSS) | 2.0 units on a scale STANDARD_DEVIATION 0 | 1.5 units on a scale STANDARD_DEVIATION 0.9 | 1.6 units on a scale STANDARD_DEVIATION 0.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 22 Participants | 25 Participants |
| Region of Enrollment United States | 4 participants | 26 participants | 30 participants |
| Sex: Female, Male Female | 4 Participants | 26 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 26 |
| other Total, other adverse events | 2 / 4 | 7 / 26 |
| serious Total, serious adverse events | 0 / 4 | 0 / 26 |
Outcome results
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.
Time frame: 52 weeks
Population: Two of the 4 natalizumab users reported post-partum relapses, compared to 7 out of the 24 who were not using natalizumab post-partum.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Natalizumab | Relapses Post Partum | 2 Participants |
| Control | Relapses Post Partum | 7 Participants |
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.
Time frame: 52 weeks
Population: Patients with MS (pwMS) with available MRI data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Natalizumab | Change in MRI | New T2 lesions | 3 Participants |
| Natalizumab | Change in MRI | NEW GdE lesions | 1 Participants |
| Control | Change in MRI | New T2 lesions | 5 Participants |
| Control | Change in MRI | NEW GdE lesions | 3 Participants |
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.
Time frame: 52 weeks
Population: Persons with MS with available EDSS scores comparing the visit closest to 52 weeks between those treated with natalizumab vs other DMTs.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab | Difference in Mean Expanded Disability Status Scale (EDSS) Scores Between Persons With MS (pwMS) Treated With Natalizumab Versus Other Disease-modifying Therapies (DMT) | 1.8 score on a scale | Standard Deviation 0.5 |
| Control | Difference in Mean Expanded Disability Status Scale (EDSS) Scores Between Persons With MS (pwMS) Treated With Natalizumab Versus Other Disease-modifying Therapies (DMT) | 1.8 score on a scale | Standard Deviation 1 |
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.
Time frame: 52 weeks
Population: Number of patients who worsened in EDSS scores comparing baseline visit to visit closest to 52 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Natalizumab | Expanded Disability Status Scale (EDSS) Worsening | 0 Participants |
| Control | Expanded Disability Status Scale (EDSS) Worsening | 4 Participants |
Secondary
Percent of Relapse Free Patients
Percent of relapse free patients between the groups
Time frame: 52 weeks
Population: Relapse free at 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Natalizumab | Percent of Relapse Free Patients | 2 Participants |
| Control | Percent of Relapse Free Patients | 17 Participants |
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.
Time frame: 52 weeks
Population: Worsening of MSIS physical, mental, or FSMC worsening comparing baseline to week 52.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Natalizumab | Change in QoL Measures | FSMC Worsening | 4 Participants |
| Natalizumab | Change in QoL Measures | MSIS Physical Worsening | 3 Participants |
| Natalizumab | Change in QoL Measures | MSIS Mental Worsening | 4 Participants |
| Control | Change in QoL Measures | MSIS Mental Worsening | 9 Participants |
| Control | Change in QoL Measures | MSIS Physical Worsening | 9 Participants |
| Control | Change in QoL Measures | FSMC Worsening | 9 Participants |
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.
Time frame: 52 weeks
Population: Persons with MS (pwMS) who participated in this study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab | 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. | 1.7 score on a scale | Standard Deviation 0.8 |
| Control | 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. | 2.3 score on a scale | Standard Deviation 1.2 |
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.
Time frame: 52 weeks
Population: Persons with MS (pwMS) who participated in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Natalizumab | 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. | 3 Participants |
| Control | 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. | 1 Participants |