Multiple Sclerosis, Relapsing-Remitting
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of natalizumab 300 milligrams (mg) subcutaneous (SC) every 4 weeks (Q4W) administrations up to 24 weeks in Japanese participants with relapsing-remitting multiple sclerosis (RRMS). The secondary objectives of the study are to evaluate other clinical and magnetic resonance imaging (MRI) measures of efficacy of natalizumab 300 mg SC Q4W administrations in Japanese participants with RRMS, to evaluate the safety, tolerability, and immunogenicity of natalizumab 300 mg SC Q4W administrations up to 48 weeks in Japanese participants with RRMS, to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of natalizumab 300 mg SC Q4W administrations up to 24 weeks and for an additional 24 weeks in Japanese participants with RRMS.
Interventions
DRUGNatalizumab
Administered as specified in the treatment arm
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Must have had a diagnosis of RRMS, as defined by the revised 2017 McDonald's criteria. All other possible neurologic diagnoses must have been reasonably excluded by means of laboratory and/or imaging studies, in the opinion of the investigator. * Must have had an EDSS score between 0.0 and 5.5, inclusive. * Must have had screening MRI or documentation of an MRI within the participant's medical record within 12 months of the screening visit that revealed 3 or more T2 hyperintense lesions consistent with MS. * Was born in Japan, and biological parents and grandparents were of Japanese origin. Key
Exclusion criteria
* Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days prior to Screening, between screening and baseline visit, or at baseline visit, including but not limited to a fever (temperature \> 37.5 degrees Celsius \[°C\]), new and persistent cough, breathlessness, or loss of taste and/or smell. * Have close contact within 14 days prior to Day 1 with a SARS-CoV-2 positive individual. * Diagnosis of primary progressive MS or secondary progressive MS. * An MS exacerbation (relapse) within 30 days prior to enrolment or, in the opinion of the investigator, the participant not having stabilized from a previous relapse prior to enrolment (Day 1). * The participant is unable to have a brain MRI scan (e.g., a participant with a metal clip to repair a cerebral aneurysm). * Previous exposure to natalizumab. Note: Other protocol specified Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Cumulative Number of New Active Lesions up to Week 24 Identified Using Brain Magnetic Resonance Imaging (MRI) Scans | Up to Week 24 | New active lesions were defined as the sum of gadolinium (Gd)-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 24 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Proportion of Participants With Any New Active Lesions at Week 24 Identified Using Brain MRI Scans | At Week 24 | New active lesions were defined as the sum of gadolinium-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions. |
| Part 2: Proportion of Participants With Any New Active Lesions at Week 48 Identified Using Brain MRI Scans | At Week 48 | New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions. |
| Change From Baseline in Number of Gd-Enhancing Lesions at Week 24 and Week 48 | Baseline, Weeks 24 and 48 | — |
| Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24 | At Week 24 | — |
| Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 48 | At Week 48 | — |
| Number of New T1 Hypointense Lesions at Week 24 | At Week 24 | — |
| Number of New T1 Hypointense Lesions at Week 48 | At Week 48 | — |
| Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52 | At Week 24, Week 48 and Week 52 | ARR is calculated as the total number of relapses that occurred during the treatment period divided by the total number of participant-years. ARR was analyzed using negative binomial regression model. |
| Proportion of Relapse-Free Participants at Week 24 and Week 52 | At Week 24 and Week 52 | A multiple sclerosis (MS) relapse was defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity. |
| Part 2: Cumulative Number of New Active Lesions up to Week 48 Identified Using Brain MRI Scans | Up to Week 48 | New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 48 weeks. |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | From first dose of study drug through 84 days after the last dose of study drug (up to Week 60) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE that has an onset date and time that is on or after the date and time of the first dose of study treatment, or that has worsened after the date and time of the first dose of study treatment through 84 days after the last dose of study treatment. |
| Percentage of Participants With Positive Anti-John Cunningham Virus (Anti-JCV) Antibodies | Baseline up to Week 48 | — |
| Number of Participants With Injection Site Reactions and Injection Reactions | From first dose of study drug through 84 days after the last dose of study drug (up to Week 60) | — |
| Percentage of Participants With Positive Anti-Natalizumab Antibodies | Baseline up to Week 48 | — |
| Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48 | Baseline, Week 24 and Week 48 | The EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory and cerebral functions, as well as walking ability. It measures the MS disability status on a scale ranging from 0 (normal) to 10 (death due to MS), with higher scores indicating more disability. A negative change from baseline indicates an improvement in the disability. |
| Serum Trough Concentration (Ctrough) of Natalizumab | Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 | — |
| Serum Concentration of Natalizumab Between Day 6 and Day 8 | Between Day 6 and Day 8 | One blood sample was collected between Day 6 and Day 8. |
| Trough Alpha-4 (α4) Integrin Saturation | Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 | — |
| Serum Soluble VCAM-1 Concentrations | Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 | — |
| Visual Analog Scale (VAS) Score at Week 24 and Week 48 | At Week 24 and Week 48 | The participant's global impression of his/her well-being was assessed with a VAS. The instrument ranges from 0 to 100 millimeters (mm), where a score of 0 denotes 'poor' and a score of 100 denotes 'excellent'. Higher scores indicates a better health state. |
Countries
Japan
Participant flow
Recruitment details
Participants were enrolled at multiple investigative sites in Japan from 26 April 2022 to 29 June 2023.
Participants by arm
| Arm | Count |
|---|---|
| Natalizumab Participants received natalizumab 300 mg, SC, Q4W for 48 weeks. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Study Terminated by Sponsor | 5 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Natalizumab |
|---|---|
| Age, Continuous | 36.6 years STANDARD_DEVIATION 11.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 17 / 21 |
| serious Total, serious adverse events | 1 / 21 |
Outcome results
Primary
Part 1: Cumulative Number of New Active Lesions up to Week 24 Identified Using Brain Magnetic Resonance Imaging (MRI) Scans
New active lesions were defined as the sum of gadolinium (Gd)-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 24 weeks.
Time frame: Up to Week 24
Population: FAS included all participants who had received at least 1 study treatment injection and had at least 1 post baseline efficacy assessment. Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab | Part 1: Cumulative Number of New Active Lesions up to Week 24 Identified Using Brain Magnetic Resonance Imaging (MRI) Scans | 0.4 number of lesions | Standard Deviation 0.6 |
95% CI: [0.18, 0.76]
Secondary
Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52
ARR is calculated as the total number of relapses that occurred during the treatment period divided by the total number of participant-years. ARR was analyzed using negative binomial regression model.
Time frame: At Week 24, Week 48 and Week 52
Population: FAS included all participants who had received at least 1 study treatment injection and had at least 1 post baseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Natalizumab | Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52 | Week 24 | 0.508 relapses per participant-year |
| Natalizumab | Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52 | Week 48 | 0.462 relapses per participant-year |
| Natalizumab | Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52 | Week 52 | 0.456 relapses per participant-year |
Secondary
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48
The EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory and cerebral functions, as well as walking ability. It measures the MS disability status on a scale ranging from 0 (normal) to 10 (death due to MS), with higher scores indicating more disability. A negative change from baseline indicates an improvement in the disability.
Time frame: Baseline, Week 24 and Week 48
Population: Safety analysis set included all participants who had received at least 1 study treatment injection. Here 'number analyzed' signifies the number of participants available for analysis at a specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Natalizumab | Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48 | Change at Week 24 | 0.02 score on a scale | Standard Deviation 0.536 |
| Natalizumab | Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48 | Change at Week 48 | -0.13 score on a scale | Standard Deviation 0.352 |
| Natalizumab | Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48 | Baseline | 1.83 score on a scale | Standard Deviation 1.544 |
Secondary
Change From Baseline in Number of Gd-Enhancing Lesions at Week 24 and Week 48
Time frame: Baseline, Weeks 24 and 48
Population: FAS included all participants who had received at least 1 study treatment injection and had at least 1 post baseline efficacy assessment. Here, 'number analyzed' signifies the number of participants available for analysis at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Natalizumab | Change From Baseline in Number of Gd-Enhancing Lesions at Week 24 and Week 48 | Baseline | 0.5 number of lesions | Standard Deviation 1.44 |
| Natalizumab | Change From Baseline in Number of Gd-Enhancing Lesions at Week 24 and Week 48 | Change at Week 24 | -0.6 number of lesions | Standard Deviation 1.47 |
| Natalizumab | Change From Baseline in Number of Gd-Enhancing Lesions at Week 24 and Week 48 | Change at Week 48 | -0.7 number of lesions | Standard Deviation 1.72 |
Secondary
Number of New T1 Hypointense Lesions at Week 24
Time frame: At Week 24
Population: FAS included all participants who had received at least 1 study treatment injection and had at least 1 post baseline efficacy assessment. Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab | Number of New T1 Hypointense Lesions at Week 24 | 0.0 number of lesions | Standard Deviation 0 |
Secondary
Number of New T1 Hypointense Lesions at Week 48
Time frame: At Week 48
Population: Week 48 analysis set included all participants in the full analysis set but excluded participants who withdrew from study due to termination of the study by Sponsor. Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab | Number of New T1 Hypointense Lesions at Week 48 | 0.2 number of lesions | Standard Deviation 0.6 |
Secondary
Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24
Time frame: At Week 24
Population: FAS included all participants who had received at least 1 study treatment injection and had at least 1 post baseline efficacy assessment. Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab | Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24 | 0.3 number of lesions | Standard Deviation 1.34 |
Secondary
Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 48
Time frame: At Week 48
Population: Week 48 analysis set included all participants in the full analysis set but excluded participants who withdrew from study due to termination of the study by Sponsor. Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab | Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 48 | 2.1 number of lesions | Standard Deviation 6.64 |
Secondary
Number of Participants With Injection Site Reactions and Injection Reactions
Time frame: From first dose of study drug through 84 days after the last dose of study drug (up to Week 60)
Population: Safety analysis set included all participants who had received at least 1 study treatment injection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Natalizumab | Number of Participants With Injection Site Reactions and Injection Reactions | Injection Site Reactions | 3 Participants |
| Natalizumab | Number of Participants With Injection Site Reactions and Injection Reactions | Injection Reactions | 2 Participants |
Secondary
Part 1: Proportion of Participants With Any New Active Lesions at Week 24 Identified Using Brain MRI Scans
New active lesions were defined as the sum of gadolinium-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions.
Time frame: At Week 24
Population: FAS included all participants who had received at least 1 study treatment injection and had at least 1 post baseline efficacy assessment. Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | Part 1: Proportion of Participants With Any New Active Lesions at Week 24 Identified Using Brain MRI Scans | 0.05 proportion of participants |
Secondary
Part 2: Cumulative Number of New Active Lesions up to Week 48 Identified Using Brain MRI Scans
New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 48 weeks.
Time frame: Up to Week 48
Population: Week 48 analysis set included all participants in the FAS but excluded participants who withdrew from study due to termination of the study by Sponsor. Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab | Part 2: Cumulative Number of New Active Lesions up to Week 48 Identified Using Brain MRI Scans | 3.1 number of lesions | Standard Deviation 8.47 |
95% CI: [0.69, 13.74]
Secondary
Part 2: Proportion of Participants With Any New Active Lesions at Week 48 Identified Using Brain MRI Scans
New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions.
Time frame: At Week 48
Population: Week 48 analysis set included all participants in the full analysis set but excluded participants who withdrew from study due to termination of the study by Sponsor. Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | Part 2: Proportion of Participants With Any New Active Lesions at Week 48 Identified Using Brain MRI Scans | 0.15 proportion of participants |
Secondary
Percentage of Participants With Positive Anti-John Cunningham Virus (Anti-JCV) Antibodies
Time frame: Baseline up to Week 48
Population: Safety analysis set included all participants who had received at least 1 study treatment injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | Percentage of Participants With Positive Anti-John Cunningham Virus (Anti-JCV) Antibodies | 57.1 percentage of participants |
Secondary
Percentage of Participants With Positive Anti-Natalizumab Antibodies
Time frame: Baseline up to Week 48
Population: Immunogenicity analysis set included all participants who had received at least 1 study treatment injection and had at least 1 postbaseline assessment for the specific parameter.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | Percentage of Participants With Positive Anti-Natalizumab Antibodies | 4.8 percentage of participants |
Secondary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE that has an onset date and time that is on or after the date and time of the first dose of study treatment, or that has worsened after the date and time of the first dose of study treatment through 84 days after the last dose of study treatment.
Time frame: From first dose of study drug through 84 days after the last dose of study drug (up to Week 60)
Population: Safety analysis set included all participants who had received at least 1 study treatment injection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Natalizumab | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 4.8 percentage of participants |
| Natalizumab | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 95.2 percentage of participants |
Secondary
Proportion of Relapse-Free Participants at Week 24 and Week 52
A multiple sclerosis (MS) relapse was defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity.
Time frame: At Week 24 and Week 52
Population: FAS included all participants who had received at least 1 study treatment injection and had at least 1 post baseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Natalizumab | Proportion of Relapse-Free Participants at Week 24 and Week 52 | Week 24 | 0.8521 proportion of participants |
| Natalizumab | Proportion of Relapse-Free Participants at Week 24 and Week 52 | Week 52 | 0.8521 proportion of participants |
Secondary
Serum Concentration of Natalizumab Between Day 6 and Day 8
One blood sample was collected between Day 6 and Day 8.
Time frame: Between Day 6 and Day 8
Population: PK analysis set included all participants who had received at least 1 study treatment injection and had at least 1 measurable serum natalizumab concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab | Serum Concentration of Natalizumab Between Day 6 and Day 8 | 29.8 mg/L | Standard Deviation 15.07 |
Secondary
Serum Soluble VCAM-1 Concentrations
Time frame: Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Population: PD analysis set included all participants who had received at least 1 study treatment of study treatment and had at least 1 assessment for α4-integrin saturation, serum soluble VCAM-1 concentration, and lymphocyte counts with lymphocyte subsets. Here 'number analyzed' signifies the number of participants available for analysis at a specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Baseline | 468.9 micrograms per liter (µg/L) | Standard Deviation 80.9 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 4 | 237.8 micrograms per liter (µg/L) | Standard Deviation 66.29 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 8 | 248.2 micrograms per liter (µg/L) | Standard Deviation 86.47 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 12 | 239.8 micrograms per liter (µg/L) | Standard Deviation 77.96 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 16 | 231.8 micrograms per liter (µg/L) | Standard Deviation 70.76 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 20 | 236.0 micrograms per liter (µg/L) | Standard Deviation 71.22 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 24 | 237.4 micrograms per liter (µg/L) | Standard Deviation 80.38 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 28 | 229.1 micrograms per liter (µg/L) | Standard Deviation 80.47 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 32 | 238.1 micrograms per liter (µg/L) | Standard Deviation 86.11 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 36 | 243.1 micrograms per liter (µg/L) | Standard Deviation 105.46 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 40 | 235.6 micrograms per liter (µg/L) | Standard Deviation 80.59 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 44 | 242.0 micrograms per liter (µg/L) | Standard Deviation 72.06 |
| Natalizumab | Serum Soluble VCAM-1 Concentrations | Week 48 | 244.1 micrograms per liter (µg/L) | Standard Deviation 87.07 |
Secondary
Serum Trough Concentration (Ctrough) of Natalizumab
Time frame: Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Population: Pharmacokinetic (PK) analysis set included all participants who had received at least 1 study treatment injection and had at least 1 measurable serum natalizumab concentration. Here 'number analyzed' signifies the number of participants available for analysis at a specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Baseline | 0.0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 4 | 10.6 milligrams per liter (mg/L) | Standard Deviation 6.59 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 8 | 15.1 milligrams per liter (mg/L) | Standard Deviation 10.11 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 12 | 18.3 milligrams per liter (mg/L) | Standard Deviation 13.22 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 16 | 21.1 milligrams per liter (mg/L) | Standard Deviation 16.12 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 20 | 20.7 milligrams per liter (mg/L) | Standard Deviation 15.13 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 24 | 23.6 milligrams per liter (mg/L) | Standard Deviation 17.77 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 28 | 22.2 milligrams per liter (mg/L) | Standard Deviation 14.01 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 32 | 20.0 milligrams per liter (mg/L) | Standard Deviation 15.7 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 36 | 22.1 milligrams per liter (mg/L) | Standard Deviation 13.95 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 40 | 19.5 milligrams per liter (mg/L) | Standard Deviation 15.31 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 44 | 22.5 milligrams per liter (mg/L) | Standard Deviation 14.76 |
| Natalizumab | Serum Trough Concentration (Ctrough) of Natalizumab | Week 48 | 24.0 milligrams per liter (mg/L) | Standard Deviation 19 |
Secondary
Trough Alpha-4 (α4) Integrin Saturation
Time frame: Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Population: Pharmacodynamic (PD) analysis set included all participants who had received at least 1 study treatment injection and had at least 1 assessment for α4-integrin saturation, serum soluble vascular cell adhesion molecule-1 (VCAM-1) concentration, and lymphocyte counts with lymphocyte subsets. Here 'number analyzed' signifies the number of participants available for analysis at a specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Baseline | 4.9 percentage | Standard Deviation 4.99 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 4 | 81.9 percentage | Standard Deviation 18.31 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 8 | 82.6 percentage | Standard Deviation 20.85 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 12 | 82.8 percentage | Standard Deviation 20.22 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 16 | 87.3 percentage | Standard Deviation 19.52 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 20 | 87.0 percentage | Standard Deviation 17.1 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 24 | 87.1 percentage | Standard Deviation 23.59 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 28 | 86.4 percentage | Standard Deviation 21.97 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 32 | 87.1 percentage | Standard Deviation 26.46 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 36 | 82.6 percentage | Standard Deviation 23.93 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 40 | 84.6 percentage | Standard Deviation 26.27 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 44 | 83.3 percentage | Standard Deviation 25.22 |
| Natalizumab | Trough Alpha-4 (α4) Integrin Saturation | Week 48 | 80.1 percentage | Standard Deviation 24.98 |
Secondary
Visual Analog Scale (VAS) Score at Week 24 and Week 48
The participant's global impression of his/her well-being was assessed with a VAS. The instrument ranges from 0 to 100 millimeters (mm), where a score of 0 denotes 'poor' and a score of 100 denotes 'excellent'. Higher scores indicates a better health state.
Time frame: At Week 24 and Week 48
Population: FAS included all participants who had received at least 1 study treatment injection and had at least 1 post baseline efficacy assessment. Here 'number analyzed' signifies the number of participants available for analysis at a specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Natalizumab | Visual Analog Scale (VAS) Score at Week 24 and Week 48 | Week 24 | 71.0 mm | Standard Deviation 22.35 |
| Natalizumab | Visual Analog Scale (VAS) Score at Week 24 and Week 48 | Week 48 | 61.5 mm | Standard Deviation 22.02 |