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Trial record 34 of 119 for:    "Progressive Muscular Atrophy"

A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Participants With Later-onset Spinal Muscular Atrophy (SMA) (CHERISH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02292537
Recruitment Status : Completed
First Posted : November 17, 2014
Results First Posted : February 21, 2018
Last Update Posted : February 21, 2018
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Spinal Muscular Atrophy
Interventions Drug: Nusinersen
Procedure: Sham procedure
Enrollment 126
Recruitment Details  
Pre-assignment Details After parental informed consent was obtained and prior to any treatment, participants entered a Screening Period of up to 21 days to determine their eligibility for the study. Of the 179 participants screened, 53 were screening failures.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description Sham comparator on Days 1, 29, 85 and 274. Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Period Title: Overall Study
Started 42 84
Completed Treatment 42 83 [1]
Completed 42 84
Not Completed 0 0
[1]
1 participant completed the study but did not complete treatments due to early study closure
Arm/Group Title Sham Procedure Nusinersen Total
Hide Arm/Group Description Sham comparator on Days 1, 29, 85 and 274. Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274. Total of all reporting groups
Overall Number of Baseline Participants 42 84 126
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 42 participants 84 participants 126 participants
3.4  (1.61) 3.8  (1.63) 3.6  (1.63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 84 participants 126 participants
Female
21
  50.0%
46
  54.8%
67
  53.2%
Male
21
  50.0%
38
  45.2%
59
  46.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 84 participants 126 participants
Hispanic or Latino
0
   0.0%
4
   4.8%
4
   3.2%
Not Hispanic or Latino
42
 100.0%
80
  95.2%
122
  96.8%
Asian
7
  16.7%
16
  19.0%
23
  18.3%
Black
1
   2.4%
1
   1.2%
2
   1.6%
White
30
  71.4%
64
  76.2%
94
  74.6%
Multiple
4
   9.5%
3
   3.6%
7
   5.6%
Hammersmith Functional Motor Scale - Expanded (HFMSE) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 42 participants 84 participants 126 participants
19.9  (7.23) 22.4  (8.33) 21.6  (8.03)
[1]
Measure Description: The HFMSE consists of 33 scored activities used to assess motor function in children with SMA. Participants were asked to do a specific activity (such as rolling) and they were then graded on the quality and execution of that movement on a scale of 0=being unable, 1=performed with some compensation, and 2=unaided. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate increased motor function.
1.Primary Outcome
Title Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score at Month 15
Hide Description The HFMSE consists of 33 scored activities used to assess motor function in children with SMA. The scale was originally developed with 20 scored activities and was devised for use in children with SMA Type 2 and Type 3 with limited ambulation to give objective information on motor ability and clinical progression. The expanded scale includes an additional module of 13 items developed to allow for evaluation of ambulatory SMA patients. Participants were asked to do a specific activity (such as rolling) and they were then graded on the quality and execution of that movement on a scale of 0=being unable, 1=performed with some compensation, and 2=unaided. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement.
Time Frame Baseline and Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Missing postbaseline HFMSE data were imputed using the multiple imputation method.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 42 84
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
-1.0
(-2.5 to 0.5)
3.9
(3.0 to 4.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Procedure, Nusinersen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment group as a factor and age at Screening and baseline HFMSE score as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.9
Confidence Interval (2-Sided) 95%
3.1 to 6.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.91
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Proportion of Participants Who Achieved a 3-Point Increase From Baseline in HFMSE Score at Month 15
Hide Description The HFMSE consists of 33 scored activities used to assess motor function in children with SMA. The scale was originally developed with 20 scored activities and was devised for use in children with SMA Type 2 and Type 3 with limited ambulation to give objective information on motor ability and clinical progression. The expanded scale includes an additional module of 13 items developed to allow for evaluation of ambulatory SMA patients. Participants were asked to do a specific activity (such as rolling) and they were then graded on the quality and execution of that movement on a scale of 0=being unable, 1=performed with some compensation, and 2=unaided. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement.
Time Frame Baseline and Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Missing postbaseline HFMSE data were imputed using multiple imputation.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 42 84
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
26.3
(12.40 to 40.22)
56.8
(45.62 to 68.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Procedure, Nusinersen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments Based on multiple imputation and logistic regression with treatment effect and adjustment for each participant's age at screening and HFMSE score at baseline.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.59
Confidence Interval (2-Sided) 95%
2.09 to 14.91
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sham Procedure, Nusinersen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Proportions
Estimated Value 30.5
Confidence Interval (2-Sided) 95%
12.74 to 48.31
Estimation Comments Difference in proportions of Nusinersen minus Sham Procedure are from multiple imputation procedure and are based on binomial proportions.
3.Secondary Outcome
Title Proportion of Participants That Achieved Any New Motor Milestone at Month 15
Hide Description New motor milestones are defined as sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone.
Time Frame Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Set: All participants with a Day 456 Visit and all participants with a time difference of at least 463 days (456 days plus a 7-day window) between the date of first dose and the date for the final analysis. Based on imputed data where there was missing data.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 34 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
5.9
(0.72 to 19.68)
19.7
(10.93 to 31.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Procedure, Nusinersen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0811
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Proportions
Estimated Value 13.8
Confidence Interval (2-Sided) 95%
-6.64 to 34.17
Estimation Comments Difference in proportions of Nusinersen minus Sham Procedure is based on exact unconditional confidence interval.
4.Secondary Outcome
Title Number of New Motor Milestones Achieved Per Participant
Hide Description New motor milestones are defined as sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone and walking alone.
Time Frame Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Set: All participants with a Day 456 Visit and all participants with a time difference of at least 463 days (456 days plus a 7-day window) between the date of first dose and the date for the final analysis. Based on imputed data where there was missing data.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 34 66
Mean (Standard Deviation)
Unit of Measure: milestones achieved
-0.2  (0.54) 0.2  (0.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Procedure, Nusinersen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
0.2 to 0.7
Estimation Comments Based on ANCOVA with treatment as a fixed effect and adjustment for each participant's age at screening and number of milestones at baseline.
5.Secondary Outcome
Title Change From Baseline in Revised Upper Limb Module (RULM) Test
Hide Description The RULM Test is used in patients with SMA to assess upper limb functional ability items that are reflective of activities of daily living (i.e., raise a can to mouth as if drinking, take a coin and place it in a box, remove the lid of a container). The RULM test has a total of 20 items with an entry item that serves as functional class identification and does not contribute to the total score. The remaining 19 scorable items reflect different functional domains and are graded on a 3-point system with a score of 0 (unable), 1 (able, with modification), and a maximum of 2 (able, no difficulty). There is only 1 item (item I) that is scored as a can/cannot score, with 1 as the highest score. Scorable items are summed for a total score range of 0-37, with higher scores increased great upper limb function. A positive change from Baseline indicates improvement.
Time Frame Baseline and Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Missing postbaseline data were imputed using multiple imputation.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 42 84
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
0.5
(-0.6 to 1.6)
4.2
(3.4 to 5.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Procedure, Nusinersen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Differenec
Estimated Value 3.7
Confidence Interval (2-Sided) 95%
2.3 to 5.0
Estimation Comments From multiple imputation procedure, based on ANCOVA with treatment as a fixed effect and adjustment for each participant's age at screening and derived total score at baseline.
6.Secondary Outcome
Title Proportion of Participants That Achieved Standing Alone
Hide Description If the participant was unable to achieve standing alone at Baseline but could achieve this at Month 15 then they were considered a responder. If they could not achieve this or if a participant terminated the study prior to the 15-month assessment due to treatment failure or death, then any imputed value was ignored and the participant was considered as a non-responder.
Time Frame Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Set: All participants with a Day 456 Visit and all participants with a time difference of at least 463 days (456 days plus a 7-day window) between the date of first dose and the date for the final analysis. Based on imputed data where there was missing data.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 34 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
2.9
(0.07 to 15.33)
1.5
(0.04 to 8.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Procedure, Nusinersen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Proportions
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-21.84 to 19.34
Estimation Comments Difference in proportions of Nusinersen minus Sham Procedure is based on exact unconditional confidence interval.
7.Secondary Outcome
Title Proportion of Participants That Achieved Walking With Assistance
Hide Description If the participant was unable to achieve walking with assistance at baseline but could achieve this at Month 15 then they were considered a responder. If they could not achieve this or if a participant terminated the study prior to the 15-month assessment due to treatment failure or death, then any imputed value was ignored and the participant was considered as a non-responder.
Time Frame Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Set: All participants with a Day 456 Visit and all participants with a time difference of at least 463 days (456 days plus a 7-day window) between the date of first dose and the date for the final analysis. Based on imputed data where there was missing data.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 34 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0
(0.00 to 10.28)
1.5
(0.04 to 8.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Procedure, Nusinersen
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Proportions
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-19.10 to 22.10
Estimation Comments Difference in proportions of Nusinersen minus Sham Procedure is based on exact unconditional confidence interval.
8.Secondary Outcome
Title Number of Participants That Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description AEs: any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAEs: an event that results in death; an event that, in the view of the investigator, places the participant at immediate risk of death; an outcome that results in a congenital anomaly/birth defect diagnosed in a child of a participant; an event that requires or prolongs inpatient hospitalization; an event that results in persistent or significant disability/incapacity. Any other medically important event that, in the opinion of the investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above.
Time Frame Baseline through Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. All participants with AEs were reported in this outcome measure, whereas in Adverse Event section there was at 5% reporting threshold to be met.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 42 84
Measure Type: Number
Unit of Measure: participants
AEs 42 78
SAEs 12 14
9.Secondary Outcome
Title Number of Participants With Clinically Significant Vital Sign Abnormalities
Hide Description Vital signs assessed for clinical significance include resting blood pressure, pulse, respiratory rate, and temperature.
Time Frame Baseline through Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Any new or worsening vital sign findings were reported as AEs and are presented in the AE/SAE section of the results.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 42 84
Measure Type: Number
Unit of Measure: participants
Systolic blood pressure <90 mmHg 33 80
Systolic blood pressure >140 mmHg 1 4
Systolic blood pressure >160 mmHg 0 2
Diastolic blood pressure <50 mmHg 31 65
Diastolic blood pressure >90 mmHg 7 11
Diastolic blood pressure >100 mmHg 2 2
Heart rate <60 beats/min 0 1
Heart rate >100 beats/min 42 84
Temperature >38.0 C 4 10
Temperature <36.0 C 14 33
Respiratory rate <12 breaths/min 0 1
Respiratory rate >20 breaths/min 42 84
10.Secondary Outcome
Title Number of Participants With Clinically Significant Weight Abnormalities
Hide Description Weight changes assessed from Baseline to Month 15.
Time Frame Baseline through Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Any new or worsening weight abnormality findings were reported as AEs and are presented in the AE/SAE section of the results.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 42 84
Measure Type: Number
Unit of Measure: participants
Weight decrease of >=7% from baseline 3 4
Weight increase of >=7% from baseline 38 77
11.Secondary Outcome
Title Number of Participants With Clinically Significant Neurological Examination Abnormalities
Hide Description Neurological changes assessed for clinical significance include assessment of mental status, level of consciousness, sensory function, motor function, cranial nerve function, and reflexes.
Time Frame Baseline through Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Neurological examination clinical significance was not collected.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Number of Participants With Clinically Significant Physical Examination Abnormalities
Hide Description Physical examination changes were assessed for clinical significance.
Time Frame Baseline through Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Physical examination clinical significance was not collected.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Number of Participants With Clinically Significant Laboratory Parameter Abnormalities
Hide Description Laboratory parameter changes assessed for clinical significance include serum chemistry, hematology, coagulation and urinalysis.
Time Frame Baseline through Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure. Any new or worsening clinical laboratory parameter findings were reported as AEs and are presented in the AE/SAE section of the results.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 42 84
Measure Type: Number
Unit of Measure: participants
Hematology: Hemoglobin - High 2 2
Hematology: Hemoglobin - Low 7 15
Hematology: Hematocrit - High 3 1
Hematology: Hematocrit - Low 6 18
Hematology: Red blood cells - High 2 2
Hematology: Red blood cells - Low 7 13
Hematology: White blood cells - High 11 12
Hematology: White blood cells - Low 10 20
Hematology: Platelet Count - High 5 10
Hematology: Platelet count - Low 10 15
Blood Chemistry: Bilirubin - Low 19 36
Blood Chemistry: Bilirubin - High 1 0
Blood Chemistry: Total bilirubin - direct - Low 5 8
Blood Chemistry: Total bilirubin - direct - High 0 0
Blood Chemistry: Total bilirubin - indirect- Low 0 0
Blood Chemistry: Total bilirubin - indirect- High 1 0
Blood Chemistry: Alkaline phosphatase - Low 1 10
Blood Chemistry: Alkaline phosphatase - High 0 0
Blood Chemistry: ALT - Low 0 1
Blood Chemistry: ALT - High 4 3
Blood Chemistry: AST - Low 0 0
Blood Chemistry: AST- High 2 3
Blood Chemistry: BUN - Low 0 2
Blood Chemistry: BUN - High 1 2
Blood Chemistry: Creatinine - Low 17 39
Blood Chemistry: Creatinine- High 0 1
Blood Chemistry: Sodium - Low 1 1
Blood Chemistry: Sodium - High 0 0
Blood Chemistry: Potassium - Low 2 0
Blood Chemistry: Potassium - High 1 0
Blood Chemistry: Chloride - Low 0 0
Blood Chemistry: Chloride - High 0 0
Blood Chemistry: Total protein - Low 1 7
Blood Chemistry: Total protein - High 9 13
Blood Chemistry: Albumin - Low 0 0
Blood Chemistry: Albumin - High 19 27
Blood Chemistry: Calcium - Low 0 1
Blood Chemistry: Calcium - High 9 20
Blood Chemistry: Phosphorus - Low 0 0
Blood Chemistry: Phosphorus - High 8 8
Blood Chemistry: Bicarbonate - Low 11 29
Blood Chemistry: Bicarbonate - High 0 0
Blood Chemistry: Glucose - Low 7 17
Blood Chemistry: Glucose - High 26 44
Blood Chemistry: Cystatin C - Low 18 36
Blood Chemistry: Cystatin C -High 0 1
Blood Chemistry: CPK - Low 0 0
Blood Chemistry: CPK - High 10 16
Urinalysis: Specific gravity - Low 0 0
Urinalysis: Specific gravity - High 2 1
Urinalysis: pH- Low 0 0
Urinalysis: pH - High 0 0
Urinalysis: Protein - High 14 43
Urinalysis: Glucose - High 2 2
Urinalysis: Ketones - High 18 29
Urinalysis: Bilirubin - High 0 0
Urinalysis: Blood - High 1 1
Urinalysis: RBC - High 1 6
Urinalysis: WBC - High 4 13
Urinalysis: Epithelial Cells - High 0 0
Urinalysis: Bacteria - High 15 24
Urinalysis: Casts - High 0 0
Urinalysis: Hyaline casts - High 1 5
Urinalysis: Crystals - High 0 0
Urinalysis: Amorphous crystals - High 10 16
Urinalysis: Calcium oxalate crystals - High 17 26
Urinalysis: Uric acid crystals - High 5 5
14.Secondary Outcome
Title Number of Participants With Abnormal, Clinically Relevant Post-Baseline Worsening in Electrocardiogram (ECG) in Results
Hide Description The number of participants with abnormal, clinically relevant worsening, defined as participants with an ECG interpreted as abnormal and clinically relevant, with a comparison with Baseline value is reported.
Time Frame Baseline through Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 42 84
Measure Type: Number
Unit of Measure: participants
2 0
15.Secondary Outcome
Title Number of Participants Taking Any Concomitant Medication Related to Dosing Procedure or Sham Procedure
Hide Description Concomitant medications include prescription and over-the-counter medications administered to participants on or after the first day of study treatment.
Time Frame Baseline through Month 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: All participants who were randomized and received at least 1 dose of study drug/sham procedure.
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description:
Sham comparator on Days 1, 29, 85 and 274.
Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
Overall Number of Participants Analyzed 42 84
Measure Type: Number
Unit of Measure: participants
42 84
Time Frame From signing of Informed Consent to the end of the Follow-up period (Month 15)
Adverse Event Reporting Description Treatment emergent AEs are presented regardless of seriousness or relationship to investigational product.
 
Arm/Group Title Sham Procedure Nusinersen
Hide Arm/Group Description Sham comparator on Days 1, 29, 85 and 274. Nusinersen 12 mg solution via intrathecal (IT) injection on Days 1, 29, 85 and 274.
All-Cause Mortality
Sham Procedure Nusinersen
Affected / at Risk (%) Affected / at Risk (%)
Total   0/42 (0.00%)   0/84 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Sham Procedure Nusinersen
Affected / at Risk (%) Affected / at Risk (%)
Total   12/42 (28.57%)   14/84 (16.67%) 
Gastrointestinal disorders     
Abdominal distension  1  0/42 (0.00%)  1/84 (1.19%) 
Constipation  1  1/42 (2.38%)  0/84 (0.00%) 
Faecaloma  1  2/42 (4.76%)  0/84 (0.00%) 
General disorders     
Pain  1  0/42 (0.00%)  1/84 (1.19%) 
Infections and infestations     
Bacteraemia  1  0/42 (0.00%)  1/84 (1.19%) 
Bronchitis  1  1/42 (2.38%)  1/84 (1.19%) 
Gastroenteritis  1  1/42 (2.38%)  2/84 (2.38%) 
Influenza  1  2/42 (4.76%)  0/84 (0.00%) 
Parainfluenzae virus infection  1  0/42 (0.00%)  1/84 (1.19%) 
Pneumonia  1  6/42 (14.29%)  2/84 (2.38%) 
Pneumonia adenoviral  1  1/42 (2.38%)  0/84 (0.00%) 
Pneumonia parainfluenzae viral  1  1/42 (2.38%)  0/84 (0.00%) 
Pneumonia viral  1  0/42 (0.00%)  3/84 (3.57%) 
Respiratory syncytial virus bronchitis  1  0/42 (0.00%)  1/84 (1.19%) 
Respiratory syncytial virus infection  1  1/42 (2.38%)  0/84 (0.00%) 
Upper respiratory tract infection  1  1/42 (2.38%)  0/84 (0.00%) 
Injury, poisoning and procedural complications     
Post lumbar puncture syndrome  1  0/42 (0.00%)  1/84 (1.19%) 
Metabolism and nutrition disorders     
Dehydration  1  2/42 (4.76%)  0/84 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia aspiration  1  0/42 (0.00%)  1/84 (1.19%) 
Respiratory distress  1  2/42 (4.76%)  2/84 (2.38%) 
Respiratory failure  1  1/42 (2.38%)  0/84 (0.00%) 
1
Term from vocabulary, MedDRA 17.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sham Procedure Nusinersen
Affected / at Risk (%) Affected / at Risk (%)
Total   42/42 (100.00%)   75/84 (89.29%) 
Gastrointestinal disorders     
Constipation  1  4/42 (9.52%)  5/84 (5.95%) 
Diarrhoea  1  3/42 (7.14%)  8/84 (9.52%) 
Vomiting  1  5/42 (11.90%)  24/84 (28.57%) 
General disorders     
Pyrexia  1  15/42 (35.71%)  36/84 (42.86%) 
Infections and infestations     
Bronchitis  1  4/42 (9.52%)  7/84 (8.33%) 
Conjunctivitis  1  2/42 (4.76%)  6/84 (7.14%) 
Ear infection  1  5/42 (11.90%)  7/84 (8.33%) 
Gastroenteritis  1  8/42 (19.05%)  9/84 (10.71%) 
Gastroenteritis viral  1  4/42 (9.52%)  8/84 (9.52%) 
Influenza  1  2/42 (4.76%)  8/84 (9.52%) 
Nasopharyngitis  1  15/42 (35.71%)  20/84 (23.81%) 
Otitis media  1  4/42 (9.52%)  5/84 (5.95%) 
Pharyngitis streptococcal  1  3/42 (7.14%)  4/84 (4.76%) 
Pneumonia  1  6/42 (14.29%)  4/84 (4.76%) 
Upper respiratory tract infection  1  19/42 (45.24%)  25/84 (29.76%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/42 (9.52%)  4/84 (4.76%) 
Back pain  1  0/42 (0.00%)  21/84 (25.00%) 
Joint contracture  1  7/42 (16.67%)  4/84 (4.76%) 
Pain in extremity  1  3/42 (7.14%)  4/84 (4.76%) 
Scoliosis  1  3/42 (7.14%)  3/84 (3.57%) 
Nervous system disorders     
Headache  1  3/42 (7.14%)  24/84 (28.57%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  9/42 (21.43%)  21/84 (25.00%) 
Epistaxis  1  0/42 (0.00%)  6/84 (7.14%) 
Rhinorrhoea  1  7/42 (16.67%)  6/84 (7.14%) 
Upper respiratory tract congestion  1  2/42 (4.76%)  5/84 (5.95%) 
1
Term from vocabulary, MedDRA 17.1
Indicates events were collected by systematic assessment
After the interim analysis of the study, the decision was made in October 2016 to terminate the study early and participants were invited for end-of-study visits.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Name/Title: Biogen Study Medical Director
Organization: Biogen
Phone: 866-633-4636
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02292537     History of Changes
Other Study ID Numbers: ISIS 396443-CS4
2014-001947-18 ( EudraCT Number )
First Submitted: November 12, 2014
First Posted: November 17, 2014
Results First Submitted: October 17, 2017
Results First Posted: February 21, 2018
Last Update Posted: February 21, 2018