Spinal Muscular Atrophy
Conditions
Keywords
Spinal Muscular Atrophy, SMA, SMN, SMNRx, ISIS-SMNRx, ISIS 396443, IONIS-SMNRx, Spinraza, Nusinersen
Brief summary
The primary objective is to examine the clinical efficacy of multiple doses of nusinersen (ISIS 396443) administered intrathecally to participants with Infantile-Onset Spinal Muscular Atrophy (SMA). The secondary objectives are to examine the safety and tolerability of multiple doses of nusinersen administered intrathecally to participants with infantile-onset SMA and to examine the cerebral spinal fluid (CSF) and plasma Pharmacokinetics (PK) of multiple doses of nusinersen administered intrathecally to participants with infantile-onset SMA.
Detailed description
This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc.. In August 2016, sponsorship of the trial was transferred to Biogen.
Interventions
DRUGnusinersen
Administered by intrathecal (IT) injection
Sponsors
Biogen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Days to 210 Days
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Genetic documentation of 5q SMA (homozygous gene deletion or mutation) * Onset of clinical signs and symptoms consistent with SMA at ≥ 21 days and \<6 months (180 days) of age * At study entry, receiving adequate nutrition and hydration (with or without gastrostomy), in the opinion of the Site Investigator * Body weight \>5th percentile for age using Center of Disease Control and Prevention (CDC) guidelines * Medical care meets and is expected to continue to meet guidelines set out in the Consensus Statement for Standard of Care in SMA (Wang et al. 2007), in the opinion of the Site Investigator * Gestational age of 35 to 42 weeks and gestation body weight ≥2 kg * Reside within approximately 9 hours ground-travel distance from a participating study center for the duration of the study. Residence \>2 hours ground-travel distance from a study center must obtain clearance from the Site Investigator and the study Medical Monitor * Able to complete all study procedures, measurements and visits and parent or guardian/participant has adequately supportive psychosocial circumstances, in the opinion of the Site Investigator
Exclusion criteria
* Hypoxemia (O2 saturation awake \<96% or O2 saturation asleep \<96%, without ventilation support) * Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period * History of brain or spinal cord disease that would interfere with the lumbar puncture (LP) procedures, CSF circulation, or safety assessments * Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter * History of bacterial meningitis * Clinically significant abnormalities in hematology or clinical chemistry parameters, as assessed by the Site Investigator, at screening that would render the participant unsuitable for inclusion * Treatment with another investigational drug (e.g., albuterol, riluzole, carnitine, creatine, sodium phenylbutyrate, salbutamol, valproate, hydroxyurea etc), biological agent, or device within 90 days prior to enrollment or anytime during the study. Any history of gene therapy or cell transplantation * The participants parent(s) or legal guardian(s) is unable to understand the nature, scope, and possible consequences of the study, or does not agree to comply with the protocol defined schedule of assessments * Ongoing medical condition that according to the Site Investigator would interfere with the conduct and assessments of the study. Examples are medical disability other than SMA that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Who Achieved Improvement in Motor Milestones as Assessed by Section 2 of the HINE at the Last Visit | Day 1352 or Early Termination | Section 2 of HINE consists of 8 independent milestone categories. Within each of these categories, participants can progress from complete absence of a motor ability (the lowest level in each category) through multiple milestones (2 to 4 levels in each category) to the highest level within the category. Overall, there are a total of 26 milestones that can be achieved across the 8 categories. Improvement was defined as any of the following: 1. An increase from baseline of 2 milestones or more, or the achievement of pincer grasp in the voluntary grasp category 2. An increase from baseline of 2 milestones or more, or achievement of touching toes in the ability to kick category 3. An increase from baseline of 1 milestone or more in any of the remaining 6 categories: head control, rolling, sitting, crawling, standing, or walking. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Improved Motor Function at the Last Visit as Assessed by the CHOP-INTEND Motor Function Scale | Day 1352 or Early Termination | The CHOP-INTEND test includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0 (worst) to 4 (best). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Improvement was defined as an increase in total CHOP INTEND score ≥4 points from baseline as of the last study visit. |
| Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Baseline, Day 1072 | CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A positive change from Baseline indicates that the number of motor neurons increased. |
| Number of Participants Experiencing Adverse Events (AEs) and/or Serious Adverse Events (SAEs) | Up to Day 1352 | AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect in the offspring of the subject (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor. |
| Event-free Survival at the End of Study | Up to Day 1638 | Event-free survival was defined as the percent of participants who were alive and did not require permanent ventilatory support (defined as tracheostomy or the need for ≥16 hours ventilation/day continuously for at least 2 weeks in the absence of an acute reversible illness) Event-free survival was estimated using Kaplan-Meier methodology. |
| PK Parameters of Nusinersen in Plasma: Maximum Concentration (Cmax) | Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) | Cmax is the maximum observed concentration of study drug in plasma. |
| PK Parameters of Nusinersen in Plasma: Time to Reach Cmax (Tmax) | Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) | Tmax is the time at which Cmax occurs. |
| PK Parameters of Nusinersen in Plasma: Area Under the Plasma Concentrations Time Curve From the Time of the IT Dose to Four Hours After Dosing (AUC0-4) | Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose ) | AUC is area under the plasma concentration-time curve from zero time (Predose) to 4 hours after IT administration of study drug. AUC was determined by using the linear trapezoidal rule. |
| Concentration of Nusinersen in Cerebrospinal Fluid (CSF) | Day 1135 (Predose) | The concentration of nusinersen in CSF was measured by using standard laboratory assays. |
Countries
Canada, United States
Participant flow
Pre-assignment details
Of the 23 participants screened, 2 were screening failures. A total of 21 participants enrolled; 1 was withdrawn from the study due to respiratory failure prior to receiving the first dose of study treatment. Twenty participants received at least 1 dose of study treatment and were included in the efficacy, safety, and PK analyses.
Participants by arm
| Arm | Count |
|---|---|
| Nusinersen 6 mg Participants received nusinersen 6 mg injections as an intrathecal (IT) bolus through a lumbar puncture (LP) on Days 1, 15, and 85. Maintenance doses of 12 mg were given on Days 253, 379, 505, 631, 757, 883, 1009, 1135, and 1261. | 4 |
| Nusinersen 12 mg Participants received nusinersen 12 mg injections as an intrathecal (IT) bolus through a lumbar puncture (LP) on Days 1, 15, and 85. Maintenance doses of 12 mg were given on Days 253, 379, 505, 631, 757, 883, 1009, 1135, and 1261. | 16 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Adverse event, serious fatal | 1 | 4 |
| Overall Study | Early study closure | 0 | 11 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Nusinersen 6 mg | Total | Nusinersen 12 mg |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 20 Participants | 16 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Distribution of Total Scores of the CHOP-INTEND Scale at Baseline 0 to 9 | 0 Participants | 0 Participants | 0 Participants |
| Distribution of Total Scores of the CHOP-INTEND Scale at Baseline 10 to 19 | 0 Participants | 2 Participants | 2 Participants |
| Distribution of Total Scores of the CHOP-INTEND Scale at Baseline 20 to 29 | 3 Participants | 9 Participants | 6 Participants |
| Distribution of Total Scores of the CHOP-INTEND Scale at Baseline 30 to 39 | 1 Participants | 7 Participants | 6 Participants |
| Distribution of Total Scores of the CHOP-INTEND Scale at Baseline 40 to 49 | 0 Participants | 1 Participants | 1 Participants |
| Distribution of Total Scores of the CHOP-INTEND Scale at Baseline 50 to 59 | 0 Participants | 0 Participants | 0 Participants |
| Distribution of Total Scores of the CHOP-INTEND Scale at Baseline 60 to 64 | 0 Participants | 1 Participants | 1 Participants |
| Hammersmith Infant Neurological Examination (HINE) Head Control Motor Milestones at Baseline All the time maintained upright | 0 Participants | 1 Participants | 1 Participants |
| Hammersmith Infant Neurological Examination (HINE) Head Control Motor Milestones at Baseline Unable to maintain head upright | 3 Participants | 16 Participants | 13 Participants |
| Hammersmith Infant Neurological Examination (HINE) Head Control Motor Milestones at Baseline Wobbles | 1 Participants | 3 Participants | 2 Participants |
| HINE Ability to Kick Motor Milestones at Baseline Kick horizontally, legs do not lift | 3 Participants | 13 Participants | 10 Participants |
| HINE Ability to Kick Motor Milestones at Baseline No kicking | 1 Participants | 6 Participants | 5 Participants |
| HINE Ability to Kick Motor Milestones at Baseline Touches leg | 0 Participants | 0 Participants | 0 Participants |
| HINE Ability to Kick Motor Milestones at Baseline Touches toes | 0 Participants | 0 Participants | 0 Participants |
| HINE Ability to Kick Motor Milestones at Baseline Upward (vertically) | 0 Participants | 1 Participants | 1 Participants |
| HINE Crawling Motor Milestones at Baseline Crawling flat on abdomen | 0 Participants | 0 Participants | 0 Participants |
| HINE Crawling Motor Milestones at Baseline Crawling on hands and knees | 0 Participants | 0 Participants | 0 Participants |
| HINE Crawling Motor Milestones at Baseline Does not lift head | 4 Participants | 18 Participants | 14 Participants |
| HINE Crawling Motor Milestones at Baseline On elbow | 0 Participants | 1 Participants | 1 Participants |
| HINE Crawling Motor Milestones at Baseline On outstretched hand | 0 Participants | 1 Participants | 1 Participants |
| HINE Rolling Motor Milestones at Baseline No rolling | 4 Participants | 19 Participants | 15 Participants |
| HINE Rolling Motor Milestones at Baseline Prone to supine | 0 Participants | 1 Participants | 1 Participants |
| HINE Rolling Motor Milestones at Baseline Rolling side to side | 0 Participants | 0 Participants | 0 Participants |
| HINE Rolling Motor Milestones at Baseline Supine to prone | 0 Participants | 0 Participants | 0 Participants |
| HINE Sitting Motor Milestones at Baseline Cannot sit | 4 Participants | 19 Participants | 15 Participants |
| HINE Sitting Motor Milestones at Baseline Pivots (rotates) | 0 Participants | 0 Participants | 0 Participants |
| HINE Sitting Motor Milestones at Baseline Props | 0 Participants | 0 Participants | 0 Participants |
| HINE Sitting Motor Milestones at Baseline Sits with support at hips | 0 Participants | 1 Participants | 1 Participants |
| HINE Sitting Motor Milestones at Baseline Stable sit | 0 Participants | 0 Participants | 0 Participants |
| HINE Standing Motor Milestones at Baseline Does not support weight | 4 Participants | 19 Participants | 15 Participants |
| HINE Standing Motor Milestones at Baseline Stands unaided | 0 Participants | 0 Participants | 0 Participants |
| HINE Standing Motor Milestones at Baseline Stands with support | 0 Participants | 0 Participants | 0 Participants |
| HINE Standing Motor Milestones at Baseline Supports weight | 0 Participants | 1 Participants | 1 Participants |
| HINE Voluntary Grasp Motor Milestones at Baseline Index finger and thumb but immature grasp | 0 Participants | 0 Participants | 0 Participants |
| HINE Voluntary Grasp Motor Milestones at Baseline No grasp | 0 Participants | 3 Participants | 3 Participants |
| HINE Voluntary Grasp Motor Milestones at Baseline Pincer grasp | 0 Participants | 0 Participants | 0 Participants |
| HINE Voluntary Grasp Motor Milestones at Baseline Uses whole hand | 4 Participants | 17 Participants | 13 Participants |
| HINE Walking Motor Milestones at Baseline Bouncing | 0 Participants | 1 Participants | 1 Participants |
| HINE Walking Motor Milestones at Baseline Cruising (walks holding on) | 0 Participants | 0 Participants | 0 Participants |
| HINE Walking Motor Milestones at Baseline No walking | 4 Participants | 19 Participants | 15 Participants |
| HINE Walking Motor Milestones at Baseline Walking independently | 0 Participants | 0 Participants | 0 Participants |
| Mean CHOP INTEND Total Scores at Baseline | 27 Units on a scale STANDARD_DEVIATION 5 | 30 Units on a scale STANDARD_DEVIATION 11 | 30 Units on a scale STANDARD_DEVIATION 12 |
| Mean CMAP Amplitude of the Ulnar Nerve at Baseline | 0.372 mV STANDARD_DEVIATION 0.177 | 0.501 mV STANDARD_DEVIATION 0.786 | 0.532 mV STANDARD_DEVIATION 0.878 |
| Mean Compound Muscle Action Potential (CMAP) Amplitude of the Peroneal Nerve at Baseline | 0.673 millivolts (mV) STANDARD_DEVIATION 0.501 | 0.549 millivolts (mV) STANDARD_DEVIATION 0.626 | 0.518 millivolts (mV) STANDARD_DEVIATION 0.664 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple Race | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 4 Participants | 19 Participants | 15 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 16 Participants | 13 Participants |
| Sex: Female, Male Female | 1 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 12 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 4 / 16 |
| other Total, other adverse events | 4 / 4 | 16 / 16 |
| serious Total, serious adverse events | 3 / 4 | 13 / 16 |
Outcome results
Primary
Percent of Participants Who Achieved Improvement in Motor Milestones as Assessed by Section 2 of the HINE at the Last Visit
Section 2 of HINE consists of 8 independent milestone categories. Within each of these categories, participants can progress from complete absence of a motor ability (the lowest level in each category) through multiple milestones (2 to 4 levels in each category) to the highest level within the category. Overall, there are a total of 26 milestones that can be achieved across the 8 categories. Improvement was defined as any of the following: 1. An increase from baseline of 2 milestones or more, or the achievement of pincer grasp in the voluntary grasp category 2. An increase from baseline of 2 milestones or more, or achievement of touching toes in the ability to kick category 3. An increase from baseline of 1 milestone or more in any of the remaining 6 categories: head control, rolling, sitting, crawling, standing, or walking.
Time frame: Day 1352 or Early Termination
Population: Safety Population: All participants who were registered and received at least 1 dose of nusinersen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nusinersen 6 mg | Percent of Participants Who Achieved Improvement in Motor Milestones as Assessed by Section 2 of the HINE at the Last Visit | 25.0 Percent of participants |
| Nusinersen 12 mg | Percent of Participants Who Achieved Improvement in Motor Milestones as Assessed by Section 2 of the HINE at the Last Visit | 68.8 Percent of participants |
Secondary
Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude
CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A positive change from Baseline indicates that the number of motor neurons increased.
Time frame: Baseline, Day 1072
Population: Safety Population: All participants who were registered and received at least 1 dose of nusinersen. Here, number of participants analyzed is the participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nusinersen 6 mg | Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Peroneal nerve | 1.88 mV | Standard Deviation 2.58 |
| Nusinersen 6 mg | Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Ulnar nerve | 0.776 mV | Standard Deviation 1.448 |
| Nusinersen 12 mg | Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Peroneal nerve | 2.81 mV | Standard Deviation 1.28 |
| Nusinersen 12 mg | Change in Neuromuscular Electrophysiology at the Last Visit as Assessed by the Change From Baseline in CMAP Amplitude | Ulnar nerve | 0.685 mV | Standard Deviation 0.415 |
Secondary
Concentration of Nusinersen in Cerebrospinal Fluid (CSF)
The concentration of nusinersen in CSF was measured by using standard laboratory assays.
Time frame: Day 1135 (Predose)
Population: PK Population: All participants who were registered and had at least 1 evaluable postdose PK sample. Here, number of participants analyzed is the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nusinersen 6 mg | Concentration of Nusinersen in Cerebrospinal Fluid (CSF) | 12.2 nanograms/milliliter (ng/mL) | Standard Deviation 8.6 |
| Nusinersen 12 mg | Concentration of Nusinersen in Cerebrospinal Fluid (CSF) | 11.1 nanograms/milliliter (ng/mL) | Standard Deviation 4.99 |
Secondary
Event-free Survival at the End of Study
Event-free survival was defined as the percent of participants who were alive and did not require permanent ventilatory support (defined as tracheostomy or the need for ≥16 hours ventilation/day continuously for at least 2 weeks in the absence of an acute reversible illness) Event-free survival was estimated using Kaplan-Meier methodology.
Time frame: Up to Day 1638
Population: Safety Population: All participants who were registered and received at least 1 dose of nusinersen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nusinersen 6 mg | Event-free Survival at the End of Study | 25.0 Percent of participants |
| Nusinersen 12 mg | Event-free Survival at the End of Study | 62.5 Percent of participants |
Secondary
Number of Participants Experiencing Adverse Events (AEs) and/or Serious Adverse Events (SAEs)
AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect in the offspring of the subject (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor.
Time frame: Up to Day 1352
Population: Safety Population: All participants who were registered and received at least 1 dose of nusinersen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nusinersen 6 mg | Number of Participants Experiencing Adverse Events (AEs) and/or Serious Adverse Events (SAEs) | Any AE | 4 participants |
| Nusinersen 6 mg | Number of Participants Experiencing Adverse Events (AEs) and/or Serious Adverse Events (SAEs) | Any SAE | 3 participants |
| Nusinersen 12 mg | Number of Participants Experiencing Adverse Events (AEs) and/or Serious Adverse Events (SAEs) | Any AE | 16 participants |
| Nusinersen 12 mg | Number of Participants Experiencing Adverse Events (AEs) and/or Serious Adverse Events (SAEs) | Any SAE | 13 participants |
Secondary
Percent of Participants With Improved Motor Function at the Last Visit as Assessed by the CHOP-INTEND Motor Function Scale
The CHOP-INTEND test includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0 (worst) to 4 (best). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Improvement was defined as an increase in total CHOP INTEND score ≥4 points from baseline as of the last study visit.
Time frame: Day 1352 or Early Termination
Population: Safety Population: All participants who were registered and received at least 1 dose of nusinersen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nusinersen 6 mg | Percent of Participants With Improved Motor Function at the Last Visit as Assessed by the CHOP-INTEND Motor Function Scale | 25.0 Percent of participants |
| Nusinersen 12 mg | Percent of Participants With Improved Motor Function at the Last Visit as Assessed by the CHOP-INTEND Motor Function Scale | 62.5 Percent of participants |
Secondary
PK Parameters of Nusinersen in Plasma: Area Under the Plasma Concentrations Time Curve From the Time of the IT Dose to Four Hours After Dosing (AUC0-4)
AUC is area under the plasma concentration-time curve from zero time (Predose) to 4 hours after IT administration of study drug. AUC was determined by using the linear trapezoidal rule.
Time frame: Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose )
Population: PK Population: All participants who were registered and had at least 1 evaluable postdose PK sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nusinersen 6 mg | PK Parameters of Nusinersen in Plasma: Area Under the Plasma Concentrations Time Curve From the Time of the IT Dose to Four Hours After Dosing (AUC0-4) | 894 ng x hr/mL | Standard Deviation 610 |
| Nusinersen 12 mg | PK Parameters of Nusinersen in Plasma: Area Under the Plasma Concentrations Time Curve From the Time of the IT Dose to Four Hours After Dosing (AUC0-4) | 2181 ng x hr/mL | Standard Deviation 1488 |
Secondary
PK Parameters of Nusinersen in Plasma: Maximum Concentration (Cmax)
Cmax is the maximum observed concentration of study drug in plasma.
Time frame: Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose )
Population: PK Population: All participants who were registered and had at least 1 evaluable postdose PK sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nusinersen 6 mg | PK Parameters of Nusinersen in Plasma: Maximum Concentration (Cmax) | 396 ng/mL | Standard Deviation 311 |
| Nusinersen 12 mg | PK Parameters of Nusinersen in Plasma: Maximum Concentration (Cmax) | 829 ng/mL | Standard Deviation 625 |
Secondary
PK Parameters of Nusinersen in Plasma: Time to Reach Cmax (Tmax)
Tmax is the time at which Cmax occurs.
Time frame: Day 1 (Predose and 1, 2, and 4 hours [hr] Postdose) and Day 2 (24 hr Postdose )
Population: PK Population: All participants who were registered and had at least 1 evaluable postdose PK sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nusinersen 6 mg | PK Parameters of Nusinersen in Plasma: Time to Reach Cmax (Tmax) | 2.09 hr | Standard Deviation 1.35 |
| Nusinersen 12 mg | PK Parameters of Nusinersen in Plasma: Time to Reach Cmax (Tmax) | 2.37 hr | Standard Deviation 1.25 |