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Trial record 1 of 2 for:    Embrace | SMA
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A Study to Assess the Safety and Tolerability of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA). (EMBRACE)

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: NCT02462759
Recruitment Status : Terminated (The study was terminated early to roll over participants to open label extension study NCT02594124.)
First Posted : June 4, 2015
Results First Posted : January 27, 2020
Last Update Posted : February 17, 2021
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 21
Recruitment Details Participants were recruited from sites in the US and Germany. Part 1 was terminated early as positive efficacy results were observed in interim analysis of study NCT02193074 and it was considered unethical to continue this part of study. Part 2 was also terminated early to rollover and continue to follow participants in study NCT02594124.
Pre-assignment Details Total of 21 participants with SMA were randomized in Part 1 of the study(7 participants in sham procedure group,14 participants in ISIS 396443 group).1 participant died in sham procedure group of Part 1.Total of 20 participants were enrolled to receive ISIS 396443 in open-label phase of Part 2.Integrated analysis was performed for Part 1 and 2.
Arm/Group Title Sham Procedure (Part 1) ISIS 396443 (Part 1) ISIS 396443 (Part 2)
Hide Arm/Group Description Sham procedure on Day 1, 15, 29, 64, 183 and 302. Single dose of 9.6 milligrams (mg) to 12.0 mg ISIS 396443, based on participant's age, intrathecal bolus injection loading doses on Day 1, 15, 29, 64 and maintenance doses, every 4 months, on Day 183 and 302. Participants who were in Sham procedure group in Part 1, received single dose of 12.0 mg ISIS 396443 intrathecal bolus injection loading doses on Day 1, 15, 29, 64 and maintenance doses, every 4 months, on Day 183, 302, 421, 540, 659 and 778 in Part 2; participants who were in ISIS 396443 group in Part 1 continued to receive a single dose of 9.6 mg to 12.0 mg ISIS 396443 intrathecal bolus injection maintenance doses on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2.
Period Title: Part 1: Double Blind
Started 7 14 0
Completed 6 14 0
Not Completed 1 0 0
Reason Not Completed
Death             1             0             0
Period Title: Part 2: Open-Label Phase
Started 0 0 20
Completed 0 0 20
Not Completed 0 0 0
Arm/Group Title Sham Procedure (Part 1) ISIS 396443 (Part 1) Total
Hide Arm/Group Description Sham procedure on Day 1, 15, 29, 64, 183 and 302. Single dose of 9.6 milligrams (mg) to 12.0 mg ISIS 396443, based on participant's age, intrathecal bolus injection loading doses on Day 1, 15, 29, 64 and maintenance doses, every 4 months, on Day 183 and 302. Total of all reporting groups
Overall Number of Baseline Participants 7 14 21
Hide Baseline Analysis Population Description
The Intent-to-treat (ITT) population include all participants who were randomized, receive at least 1 dose of ISIS 396443 or sham procedure.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 7 participants 14 participants 21 participants
24.4  (13.83) 19.4  (10.12) 21.1  (11.39)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 14 participants 21 participants
Female
5
  71.4%
5
  35.7%
10
  47.6%
Male
2
  28.6%
9
  64.3%
11
  52.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 7 participants 14 participants 21 participants
Ethnicity: Hispanic or Latino
2
  28.6%
1
   7.1%
3
  14.3%
Ethnicity: Not Hispanic or Latino
4
  57.1%
9
  64.3%
13
  61.9%
Ethnicity: Not reported due to confidentiality
1
  14.3%
4
  28.6%
5
  23.8%
Race: Asian
3
  42.9%
2
  14.3%
5
  23.8%
Race: White
2
  28.6%
7
  50.0%
9
  42.9%
Race: Other
1
  14.3%
1
   7.1%
2
   9.5%
Race: Not reported due to confidentiality
1
  14.3%
4
  28.6%
5
  23.8%
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description 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 laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.
Time Frame Part 1 and 2: From first dose/sham procedure to end of study (up to 1080 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure.
Arm/Group Title Sham Procedure in Part 1 ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of sham procedure on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 7 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
6
  85.7%
6
 100.0%
14
 100.0%
SAEs
3
  42.9%
4
  66.7%
9
  64.3%
2.Primary Outcome
Title Number of Participants With Change From Baseline in Clinical Laboratory Parameters
Hide Description Clinically significant changes in laboratory parameters were evaluated for assessing the safety of ISIS 396443.
Time Frame Part 1 and 2: From first dose/sham procedure to end of study (up to 1080 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure.
Arm/Group Title Sham Procedure in Part 1 ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of sham procedure on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 7 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Number of Participants With Change From Baseline in Electrocardiograms (ECGs)
Hide Description Clinically significant changes in ECG measurements were evaluated for assessing the safety of ISIS 396443.
Time Frame Part 1: Day 2, 29 and 422; Part 2: Day 1 to 596
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure.
Arm/Group Title Sham Procedure in Part 1 ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of sham procedure on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 7 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Number of Participants With Change From Baseline in Vital Signs
Hide Description Clinically significant changes in vital signs were evaluated for assessing the safety of ISIS 396443. Vital signs that were assessed included resting systolic and diastolic blood pressure, pulse rate, respiratory rate, temperature, pulse oximetry, and transcutaneous carbon dioxide.
Time Frame Part 1: Day 2, 29 and 422; Part 2: Day 1 to 596
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure.
Arm/Group Title Sham Procedure in Part 1 ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of sham procedure on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 7 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Change From Baseline in Head Circumference
Hide Description Participants were analyzed for change in growth parameter of head circumference to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the head circumference percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138.
Time Frame Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants who were evaluated for the specified time points. Due the early termination of Part 2, no participants in the ISIS 396443 Part 2(participants on sham in Part 1) were on study beyond Day 659.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Mean (Standard Deviation)
Unit of Measure: centimeter (cm)
Baseline Number Analyzed 6 participants 14 participants
50.8  (3.83) 47.3  (1.51)
Change at Day 15 Number Analyzed 5 participants 14 participants
-0.7  (3.34) 0.1  (0.36)
Change at Day 29 Number Analyzed 6 participants 13 participants
0.0  (2.76) 0.3  (0.65)
Change at Day 64 Number Analyzed 6 participants 14 participants
0.1  (2.64) 0.5  (0.73)
Change at Day 183 Number Analyzed 6 participants 14 participants
0.3  (3.10) 1.0  (1.12)
Change at Day 302 Number Analyzed 6 participants 14 participants
1.0  (3.28) 1.6  (1.05)
Change at Day 422 Number Analyzed 6 participants 13 participants
0.9  (2.47) 2.0  (1.24)
Change at Day 540 Number Analyzed 6 participants 14 participants
1.3  (1.97) 2.5  (1.24)
Change at Day 659 Number Analyzed 6 participants 14 participants
1.5  (2.53) 2.6  (1.37)
Change at Day 778 Number Analyzed 0 participants 14 participants
2.8  (0.92)
Change at Day 898 Number Analyzed 0 participants 12 participants
3.5  (1.05)
Change at Day 1018 Number Analyzed 0 participants 5 participants
3.5  (2.06)
Change at Day 1138 Number Analyzed 0 participants 1 participants
4.0  (0)
6.Primary Outcome
Title Change From Baseline in Chest Circumference
Hide Description Participants were analyzed for change in growth parameter of chest circumference to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the chest circumference percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days>1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138.
Time Frame Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants who were evaluated for the specified time points. Due the early termination of Part 2, no participants in the ISIS 396443 Part 2(participants on sham in Part 1) were on study beyond Day 659.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Mean (Standard Deviation)
Unit of Measure: cm
Baseline Number Analyzed 6 participants 14 participants
51.3  (5.45) 46.9  (3.91)
Change at Day 15 Number Analyzed 5 participants 14 participants
-0.2  (3.86) -0.4  (1.53)
Change at Day 29 Number Analyzed 6 participants 13 participants
-1.1  (2.70) 0.2  (1.39)
Change at Day 64 Number Analyzed 6 participants 14 participants
-0.9  (3.50) 0.2  (1.92)
Change at Day 183 Number Analyzed 6 participants 14 participants
0.2  (3.04) 1.4  (2.02)
Change at Day 302 Number Analyzed 6 participants 14 participants
1.2  (3.07) 1.6  (2.86)
Change at Day 422 Number Analyzed 6 participants 14 participants
0.5  (3.72) 2.8  (2.73)
Change at Day 540 Number Analyzed 6 participants 14 participants
1.8  (2.42) 3.8  (3.23)
Change at Day 659 Number Analyzed 6 participants 14 participants
2.9  (3.85) 5.1  (3.29)
Change at Day 778 Number Analyzed 0 participants 14 participants
5.5  (3.52)
Change at Day 898 Number Analyzed 0 participants 12 participants
7.1  (3.04)
Change at Day 1018 Number Analyzed 0 participants 5 participants
9.7  (4.92)
Change at Day 1138 Number Analyzed 0 participants 1 participants
9.1  (0)
7.Primary Outcome
Title Change From Baseline in Arm Circumference
Hide Description Participants were analyzed for change in growth parameter of arm circumference to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the arm circumference percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138.
Time Frame Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants who were evaluated for the specified time points. Due the early termination of Part 2, no participants in the ISIS 396443 Part 2(participants on sham in Part 1) were on study beyond Day 659.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Mean (Standard Deviation)
Unit of Measure: cm
Baseline Number Analyzed 6 participants 14 participants
16.2  (1.19) 14.5  (1.85)
Change at Day 15 Number Analyzed 5 participants 14 participants
-0.4  (1.04) 0.3  (0.61)
Change at Day 29 Number Analyzed 6 participants 13 participants
-0.5  (1.08) -0.1  (0.54)
Change at Day 64 Number Analyzed 6 participants 14 participants
-0.3  (0.49) -0.4  (0.89)
Change at Day 183 Number Analyzed 6 participants 14 participants
0.0  (0.89) 0.0  (0.85)
Change at Day 302 Number Analyzed 6 participants 14 participants
-0.6  (0.89) 0.2  (1.17)
Change at Day 422 Number Analyzed 6 participants 14 participants
-0.6  (1.82) 0.5  (1.71)
Change at Day 540 Number Analyzed 6 participants 14 participants
-0.2  (2.24) 0.5  (1.89)
Change at Day 659 Number Analyzed 6 participants 14 participants
0.6  (0.93) 0.6  (1.93)
Change at Day 778 Number Analyzed 0 participants 14 participants
0.0  (2.18)
Change at Day 898 Number Analyzed 0 participants 12 participants
0.8  (2.70)
Change at Day 1018 Number Analyzed 0 participants 5 participants
1.0  (2.02)
Change at Day 1138 Number Analyzed 0 participants 1 participants
1.5  (0)
8.Primary Outcome
Title Change From Baseline in Weight for Age
Hide Description Participants were analyzed for change in growth parameter of weight for age to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the weight for age percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138.
Time Frame Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants who were evaluated for the specified time points. Due the early termination of Part 2, no participants in the ISIS 396443 Part 2(participants on sham in Part 1) were on study beyond Day 659.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Mean (Standard Deviation)
Unit of Measure: kilogram (kg)
Baseline Number Analyzed 6 participants 14 participants
42.5  (40.87) 25.3  (28.41)
Change at Day 15 Number Analyzed 6 participants 14 participants
-1.3  (1.41) 3.6  (12.12)
Change at Day 29 Number Analyzed 6 participants 14 participants
-2.4  (1.61) -1.4  (4.82)
Change at Day 64 Number Analyzed 6 participants 14 participants
-2.9  (2.58) 0.5  (8.17)
Change at Day 183 Number Analyzed 6 participants 14 participants
-3.8  (6.93) -5.9  (8.73)
Change at Day 302 Number Analyzed 6 participants 14 participants
-10.1  (13.04) -8.0  (15.42)
Change at Day 422 Number Analyzed 6 participants 14 participants
-6.3  (9.45) -7.5  (17.52)
Change at Day 540 Number Analyzed 6 participants 14 participants
-7.0  (6.56) -8.1  (17.26)
Change at Day 659 Number Analyzed 6 participants 14 participants
-8.5  (17.64) -10.5  (22.23)
Change at Day 778 Number Analyzed 0 participants 14 participants
-13.2  (16.95)
Change at Day 898 Number Analyzed 0 participants 12 participants
-10.5  (24.10)
Change at Day 1018 Number Analyzed 0 participants 5 participants
-7.0  (34.14)
Change at Day 1138 Number Analyzed 0 participants 1 participants
0.3  (0)
9.Primary Outcome
Title Change From Baseline in Weight
Hide Description Participants were analyzed for change in growth parameter of weight to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the weight percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138.
Time Frame Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants who were evaluated for the specified time points. Due the early termination of Part 2, no participants in the ISIS 396443 Part 2(participants on sham in Part 1) were on study beyond Day 659.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Mean (Standard Deviation)
Unit of Measure: kg
Baseline Number Analyzed 6 participants 14 participants
13.0  (2.00) 9.5  (1.37)
Change at Day 15 Number Analyzed 6 participants 14 participants
-0.1  (0.23) 0.2  (0.44)
Change at Day 29 Number Analyzed 6 participants 14 participants
-0.1  (0.26) 0.1  (0.23)
Change at Day 64 Number Analyzed 6 participants 14 participants
0.0  (0.39) 0.4  (0.42)
Change at Day 183 Number Analyzed 6 participants 14 participants
0.8  (0.61) 0.7  (0.48)
Change at Day 302 Number Analyzed 6 participants 14 participants
0.7  (1.04) 1.3  (0.87)
Change at Day 422 Number Analyzed 6 participants 14 participants
1.8  (1.03) 1.9  (1.02)
Change at Day 540 Number Analyzed 6 participants 14 participants
2.3  (1.33) 2.2  (1.17)
Change at Day 659 Number Analyzed 6 participants 14 participants
3.1  (1.39) 2.8  (1.41)
Change at Day 778 Number Analyzed 0 participants 14 participants
3.2  (1.87)
Change at Day 898 Number Analyzed 0 participants 12 participants
3.9  (2.86)
Change at Day 1018 Number Analyzed 0 participants 5 participants
4.3  (1.96)
Change at Day 1138 Number Analyzed 0 participants 1 participants
5.0  (0)
10.Primary Outcome
Title Change From Baseline in Head to Chest Circumference (HCC) Ratio
Hide Description Participants were analyzed for change in growth parameter of HCC to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the HCC circumference percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138.
Time Frame Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants who were evaluated for the specified time points. Due the early termination of Part 2, no participants in the ISIS 396443 Part 2(participants on sham in Part 1) were on study beyond Day 659.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Mean (Standard Deviation)
Unit of Measure: ratio
Baseline Number Analyzed 6 participants 14 participants
1.0  (0.05) 1.0  (0.08)
Change at Day 15 Number Analyzed 5 participants 14 participants
0.0  (0.03) 0.0  (0.03)
Change at Day 29 Number Analyzed 6 participants 13 participants
0.0  (0.04) 0.0  (0.04)
Change at Day 64 Number Analyzed 6 participants 14 participants
0.0  (0.04) 0.0  (0.05)
Change at Day 183 Number Analyzed 6 participants 14 participants
0.0  (0.05) 0.0  (0.05)
Change at Day 302 Number Analyzed 6 participants 14 participants
0.0  (0.03) 0.0  (0.06)
Change at Day 422 Number Analyzed 6 participants 13 participants
0.0  (0.04) 0.0  (0.06)
Change at Day 540 Number Analyzed 6 participants 14 participants
0.0  (0.03) 0.0  (0.06)
Change at Day 659 Number Analyzed 6 participants 14 participants
0.0  (0.03) -0.1  (0.06)
Change at Day 778 Number Analyzed 0 participants 14 participants
-0.1  (0.07)
Change at Day 898 Number Analyzed 0 participants 12 participants
-0.1  (0.06)
Change at Day 1018 Number Analyzed 0 participants 5 participants
-0.1  (0.10)
Change at Day 1138 Number Analyzed 0 participants 1 participants
-0.1  (0)
11.Primary Outcome
Title Change From Baseline in Body Length
Hide Description Participants were analyzed for change in growth parameter of body length to evaluate clinical efficacy. WHO Child Growth Standards were used to determine the body length percentile. Study days were windowed for integrated analysis and labelled as follows: Days <=1 as Baseline; Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138.
Time Frame Part 2: Baseline, Day 15, 29, 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants who were evaluated for the specified time points. Due the early termination of Part 2, no participants in the ISIS 396443 Part 2(participants on sham in Part 1) were on study beyond Day 659.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Mean (Standard Deviation)
Unit of Measure: cm
Baseline Number Analyzed 6 participants 14 participants
95.0  (9.48) 79.9  (5.25)
Change at Day 15 Number Analyzed 5 participants 14 participants
-1.6  (3.19) -0.1  (1.81)
Change at Day 29 Number Analyzed 6 participants 13 participants
-0.9  (3.49) 0.9  (1.66)
Change at Day 64 Number Analyzed 6 participants 14 participants
0.5  (4.77) 1.8  (2.40)
Change at Day 183 Number Analyzed 6 participants 14 participants
3.0  (4.16) 5.6  (2.36)
Change at Day 302 Number Analyzed 6 participants 14 participants
2.9  (5.76) 7.1  (2.70)
Change at Day 422 Number Analyzed 6 participants 14 participants
4.2  (5.42) 9.3  (3.09)
Change at Day 540 Number Analyzed 6 participants 14 participants
4.6  (7.18) 11.6  (3.93)
Change at Day 659 Number Analyzed 6 participants 14 participants
10.8  (4.12) 13.1  (3.79)
Change at Day 778 Number Analyzed 0 participants 14 participants
14.8  (3.94)
Change at Day 898 Number Analyzed 0 participants 12 participants
17.2  (5.62)
Change at Day 1018 Number Analyzed 0 participants 5 participants
19.0  (6.67)
Change at Day 1138 Number Analyzed 0 participants 1 participants
15.8  (0)
12.Primary Outcome
Title Number of Participants With Change From Baseline in Neurological Examination Outcomes
Hide Description Neurological examinations included assessment of mental status, level of consciousness, sensory function, motor function, cranial nerve function, reflexes, mood, speech/language and hearing.
Time Frame Part 1: Baseline to Day 422; Part 2: Baseline to Day 596
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure.
Arm/Group Title Sham Procedure in Part 1 ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of sham procedure on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 7 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
Mental Status
0
   0.0%
1
  16.7%
3
  21.4%
Level of consciousness
0
   0.0%
1
  16.7%
2
  14.3%
Sensory function
0
   0.0%
0
   0.0%
0
   0.0%
Motor function
0
   0.0%
0
   0.0%
0
   0.0%
Cranial nerve function: Eye Movement
0
   0.0%
0
   0.0%
1
   7.1%
Cranial nerve function: Vision
0
   0.0%
0
   0.0%
1
   7.1%
Reflexes
0
   0.0%
0
   0.0%
0
   0.0%
Mood
5
  71.4%
5
  83.3%
12
  85.7%
Speech/Language
0
   0.0%
1
  16.7%
1
   7.1%
Hearing
0
   0.0%
0
   0.0%
0
   0.0%
13.Primary Outcome
Title Number of Participants With Change From Baseline in Activated Partial Thromboplastin Time [aPTT]
Hide Description Activated partial thromboplastin time was evaluated to assess safety. "Shift to low" measured change in normal, high and unknown values of aPTT at baseline to low values postbaseline. "Shift to high" measured change in normal, high and unknown values of aPTT at baseline to high values postbaseline.
Time Frame Part 2: Up to 1080 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants whose baseline value was not low (or high) and who had at least one post-baseline measurement.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
Shift to Low Number Analyzed 6 participants 9 participants
0
   0.0%
0
   0.0%
Shift to High Number Analyzed 6 participants 10 participants
0
   0.0%
0
   0.0%
14.Primary Outcome
Title Number of Participants With Change From Baseline in Partial Thromboplastin Time [PTT]
Hide Description PTT was evaluated to assess safety. "Shift to low" measured change in normal, high and unknown values of PTT at baseline to low values postbaseline. "Shift to high" measured change in normal, high and unknown values of PTT at baseline to high values postbaseline.
Time Frame Part 2: Up to 1080 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants whose baseline value was not low (or high) and who had at least one post-baseline measurement.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
Shift to Low Number Analyzed 5 participants 6 participants
0
   0.0%
0
   0.0%
Shift to High Number Analyzed 5 participants 6 participants
0
   0.0%
0
   0.0%
15.Primary Outcome
Title Number of Participants With Change From Baseline in International Normalized Ratio [INR])
Hide Description INR was evaluated to assess safety. "Shift to low" measured change in normal, high and unknown values of INR at baseline to low values postbaseline. "Shift to high" measured change in normal, high and unknown values of INR at baseline to high values postbaseline.
Time Frame Part 2: Up to 1080 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure. Number analyzed indicates participants whose baseline value was not low (or high) and who had at least one post-baseline measurement.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
Shift to Low Number Analyzed 4 participants 7 participants
0
   0.0%
0
   0.0%
Shift to High Number Analyzed 4 participants 7 participants
0
   0.0%
0
   0.0%
16.Primary Outcome
Title Number of Participants With Presence of Urine Total Protein Post-baseline
Hide Description Urine total protein was evaluated to assess safety.
Time Frame Part 2: Up to 1080 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline
0
   0.0%
1
   7.1%
High/Postive
2
  33.3%
8
  57.1%
17.Secondary Outcome
Title Plasma Concentration of ISIS 396443 in Part 2 of Study in Participants Who Received Sham Procedure in Part 1 of the Study
Hide Description Study days were windowed for integrated analysis and labelled as follows: Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659.
Time Frame Pre-dose on Days 64, 183, 540 and 659
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) population included all participants who were randomized and have at least 1 evaluable post dose or post sham-procedure PK sample.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1)
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
Day 64 1.983  (0.7320)
Day 183 0.776  (0.3994)
Day 540 0.425  (0.2200)
Day 659 0.365  (0.1146)
18.Secondary Outcome
Title Plasma Concentration of ISIS 396443 in Part 1 and 2 of Study in Participants Who Received ISIS 396443 in Part 1 of the Study
Hide Description Study days were windowed for integrated analysis and labelled as follows: Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018;Days >1078 to <= 1198 as Day 1138.
Time Frame Pre-dose on Days 64, 183, 302, 422, 540, 659, 778, 898, 1018 and 1138
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who were randomized and have at least 1 evaluable post dose or post sham-procedure PK sample. Number analyzed indicates participants who were evaluated for the specified time points.
Arm/Group Title ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 64 Number Analyzed 14 participants
2.139  (0.8811)
Day 183 Number Analyzed 13 participants
1.059  (0.5569)
Day 302 Number Analyzed 5 participants
0.667  (0.1852)
Day 422 Number Analyzed 9 participants
0.858  (0.4636)
Day 540 Number Analyzed 5 participants
0.608  (0.2736)
Day 659 Number Analyzed 9 participants
0.739  (0.2812)
Day 778 Number Analyzed 5 participants
0.590  (0.3414)
Day 898 Number Analyzed 10 participants
0.661  (0.2558)
Day 1018 Number Analyzed 4 participants
0.329  (0.1020)
Day 1138 Number Analyzed 1 participants
0.423  (0)
19.Secondary Outcome
Title Cerebrospinal Fluid (CSF) Concentration of ISIS 396443 in Part 2 of Study in Participants Who Received Sham Procedure in Part 1 of the Study
Hide Description CSF samples were analyzed for ISIS 396443 concentrations in participants. Study days were windowed for integrated analysis and labelled as follows: Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540.
Time Frame Pre-dose on Days 15, 29, 64, 183, 302, 422 and 540
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who were randomized and have at least 1 evaluable post dose or post sham-procedure PK sample. Number analyzed indicates participants who were evaluated for the specified time points.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1)
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Overall Number of Participants Analyzed 6
Mean (Standard Error)
Unit of Measure: ng/mL
Day 1 Number Analyzed 5 participants
NA [1]   (NA)
Day 15 Number Analyzed 5 participants
3.094  (1.2172)
Day 29 Number Analyzed 6 participants
4.805  (2.6706)
Day 64 Number Analyzed 6 participants
4.357  (2.3229)
Day 183 Number Analyzed 6 participants
4.110  (2.4535)
Day 302 Number Analyzed 6 participants
5.397  (2.7503)
Day 422 Number Analyzed 6 participants
6.460  (2.9428)
Day 540 Number Analyzed 6 participants
8.405  (6.2423)
[1]
Mean was below the lower limit of quantification (LLOQ) hence standard deviation was not evaluated. LLOQ is 50 picogram per millilitre.
20.Secondary Outcome
Title CSF Concentration of ISIS 396443 in Part 1 and 2 of Study in Participants Who Received ISIS 396443 in Part 1 of the Study
Hide Description CSF samples were analyzed for ISIS 396443 concentrations in participants. Study days were windowed for integrated analysis and labelled as follows: Days >1 to <= 22 as Day 15;Days >22 to <=47 as Day 29;Days >47 to <= 123 as Day 64;Days >123 to <=242 as Day 183;Days >242 to <=362 as Day 302;Days >362 to <=482 as Day 422;Days >482 to <= 600 as Day 540;Days >600 to <= 719 as Day 659;Days >719 to <= 838 as Day 778;Days >838 to <= 958 as Day 898;Days >958 to <= 1078 as Day 1018.
Time Frame Pre-dose on Days 15, 29, 64, 183, 302, 422, 540, 659, 778, 898 and 1018
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who were randomized and have at least 1 evaluable post dose or post sham-procedure PK sample. Number analyzed indicates participants who were evaluated for the specified time points.
Arm/Group Title ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 Number Analyzed 8 participants
NA [1]   (NA)
Day 15 Number Analyzed 13 participants
3.925  (2.0525)
Day 29 Number Analyzed 14 participants
7.273  (4.4786)
Day 64 Number Analyzed 14 participants
7.176  (2.8487)
Day 183 Number Analyzed 14 participants
8.226  (3.6450)
Day 302 Number Analyzed 13 participants
8.968  (3.1188)
Day 422 Number Analyzed 13 participants
9.251  (4.0631)
Day 540 Number Analyzed 14 participants
9.026  (2.6864)
Day 659 Number Analyzed 14 participants
9.785  (3.3725)
Day 778 Number Analyzed 13 participants
8.632  (2.4131)
Day 898 Number Analyzed 8 participants
11.321  (8.9351)
Day 1018 Number Analyzed 1 participants
7.010  (0)
[1]
Mean was below the lower limit of quantification (LLOQ) hence standard deviation was not evaluated. LLOQ is 50 picogram per millilitre.
21.Secondary Outcome
Title Number of Participants With Plasma Antibodies to ISIS 396443
Hide Description [Not Specified]
Time Frame Part 2: Baseline to Day 596
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure.
Arm/Group Title ISIS 396443 Part 2(Participants on Sham in Part 1) ISIS 396443 Part 1 & 2
Hide Arm/Group Description:
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study.
Overall Number of Participants Analyzed 6 14
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
Time Frame From start to end of study (up to 1133 days)
Adverse Event Reporting Description The safety population included all participants who were randomized and received at least 1 dose of study treatment or sham procedure.
 
Arm/Group Title Sham Procedure in Part 1 ISIS 396443 Part 1 & 2 ISIS 396443 Part 2(Participants on Sham in Part 1)
Hide Arm/Group Description Participants who received single dose of sham procedure on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study. Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183 and 302 in Part 1 of the study and then received single dose of ISIS 396443 on Day 1, 120, 239, 358, 477, 596 and 715 in Part 2 of the study. Participants who received single dose of ISIS 396443 on Day 1, 15, 29, 64, 183, 302, 421, 540, 659 and 778 in Part 2.
All-Cause Mortality
Sham Procedure in Part 1 ISIS 396443 Part 1 & 2 ISIS 396443 Part 2(Participants on Sham in Part 1)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/7 (14.29%)   0/14 (0.00%)   0/6 (0.00%) 
Hide Serious Adverse Events
Sham Procedure in Part 1 ISIS 396443 Part 1 & 2 ISIS 396443 Part 2(Participants on Sham in Part 1)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/7 (42.86%)   9/14 (64.29%)   4/6 (66.67%) 
Cardiac disorders       
Cardio-respiratory arrest † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Sinus bradycardia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Gastrointestinal disorders       
Dental caries † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Dysphagia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Vomiting † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
General disorders       
Brain death † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Infections and infestations       
Bronchiolitis † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Bronchitis moraxella † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Enterovirus infection † 1  1/7 (14.29%)  0/14 (0.00%)  1/6 (16.67%) 
Gastroenteritis † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Gastroenteritis norovirus † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Gastroenteritis viral † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Lower respiratory tract infection † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Parainfluenzae virus infection † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Pneumonia † 1  0/7 (0.00%)  7/14 (50.00%)  3/6 (50.00%) 
Pneumonia haemophilus † 1  1/7 (14.29%)  0/14 (0.00%)  1/6 (16.67%) 
Pneumonia moraxella † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Pneumonia pneumococcal † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Pneumonia respiratory syncytial viral † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Respiratory syncytial virus bronchiolitis † 1  0/7 (0.00%)  2/14 (14.29%)  1/6 (16.67%) 
Respiratory syncytial virus infection † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Respiratory tract infection † 1  1/7 (14.29%)  1/14 (7.14%)  1/6 (16.67%) 
Rhinovirus infection † 1  1/7 (14.29%)  2/14 (14.29%)  2/6 (33.33%) 
Staphylococcal infection † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Nasopharyngitis † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Injury, poisoning and procedural complications       
Femur fracture † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Metabolism and nutrition disorders       
Failure to thrive † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Metabolic acidosis † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Nervous system disorders       
Hypoxic-ischaemic encephalopathy † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Loss of consciousness † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure † 1  1/7 (14.29%)  1/14 (7.14%)  1/6 (16.67%) 
Bronchial secretion retention † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Cough † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Hypoventilation † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Hypoxia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Pneumonia aspiration † 1  0/7 (0.00%)  3/14 (21.43%)  1/6 (16.67%) 
Respiratory distress † 1  1/7 (14.29%)  2/14 (14.29%)  2/6 (33.33%) 
Respiratory failure † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sham Procedure in Part 1 ISIS 396443 Part 1 & 2 ISIS 396443 Part 2(Participants on Sham in Part 1)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/7 (85.71%)   14/14 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders       
Anaemia † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Leukocytosis † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Thrombocytosis † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Cardiac disorders       
Bradycardia † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Sinus tachycardia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Tachycardia † 1  2/7 (28.57%)  3/14 (21.43%)  0/6 (0.00%) 
Congenital, familial and genetic disorders       
Congenital nystagmus † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Plagiocephaly † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Ear and labyrinth disorders       
Ear pain † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Eye disorders       
Myopia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Ocular hyperaemia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Gastrointestinal disorders       
Abdominal discomfort † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Abdominal pain upper † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Aphthous ulcer † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Constipation † 1  1/7 (14.29%)  4/14 (28.57%)  0/6 (0.00%) 
Dental caries † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Diarrhoea † 1  0/7 (0.00%)  5/14 (35.71%)  1/6 (16.67%) 
Dyspepsia † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Dysphagia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Flatulence † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Gastrointestinal haemorrhage † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Gastrooesophageal reflux disease † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Gingival pain † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Lip swelling † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Oral contusion † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Salivary hypersecretion † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Teething † 1  2/7 (28.57%)  2/14 (14.29%)  0/6 (0.00%) 
Vomiting † 1  1/7 (14.29%)  7/14 (50.00%)  2/6 (33.33%) 
General disorders       
Asthenia † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Complication associated with device † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Fatigue † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Influenza like illness † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Oedema peripheral † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Pyrexia † 1  1/7 (14.29%)  12/14 (85.71%)  4/6 (66.67%) 
Swelling † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Immune system disorders       
Drug hypersensitivity † 1  1/7 (14.29%)  1/14 (7.14%)  0/6 (0.00%) 
Seasonal allergy † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Infections and infestations       
Bronchiolitis † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Bronchitis † 1  1/7 (14.29%)  2/14 (14.29%)  0/6 (0.00%) 
Cellulitis † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Conjunctivitis † 1  0/7 (0.00%)  4/14 (28.57%)  0/6 (0.00%) 
Conjunctivitis bacterial † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Ear infection † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Gastroenteritis † 1  0/7 (0.00%)  5/14 (35.71%)  0/6 (0.00%) 
Gastroenteritis adenovirus † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Gastroenteritis norovirus † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Gastroenteritis viral † 1  0/7 (0.00%)  2/14 (14.29%)  1/6 (16.67%) 
Hand-foot-and-mouth disease † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Influenza † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Lower respiratory tract infection † 1  0/7 (0.00%)  5/14 (35.71%)  1/6 (16.67%) 
Otitis externa † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Otitis media † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Otitis media acute † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Parainfluenzae virus infection † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Pharyngitis streptococcal † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Pneumonia † 1  0/7 (0.00%)  7/14 (50.00%)  2/6 (33.33%) 
Pneumonia haemophilus † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Pneumonia moraxella † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Respiratory syncytial virus infection † 1  0/7 (0.00%)  3/14 (21.43%)  1/6 (16.67%) 
Respiratory tract infection † 1  1/7 (14.29%)  5/14 (35.71%)  1/6 (16.67%) 
Rhinovirus infection † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Sinusitis † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Stoma site infection † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Upper respiratory tract infection † 1  2/7 (28.57%)  9/14 (64.29%)  3/6 (50.00%) 
Urinary tract infection † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Vaginal infection † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Viral rash † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Viral upper respiratory tract infection † 1  1/7 (14.29%)  5/14 (35.71%)  1/6 (16.67%) 
Injury, poisoning and procedural complications       
Ankle fracture † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Arthropod bite † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Contusion † 1  1/7 (14.29%)  1/14 (7.14%)  0/6 (0.00%) 
Fall † 1  0/7 (0.00%)  1/14 (7.14%)  2/6 (33.33%) 
Femur fracture † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Incision site erythema † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Incision site pain † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Joint dislocation † 1  0/7 (0.00%)  3/14 (21.43%)  0/6 (0.00%) 
Laceration † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Muscle strain † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Procedural pain † 1  0/7 (0.00%)  3/14 (21.43%)  0/6 (0.00%) 
Procedural vomiting † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Skin abrasion † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Stoma site haemorrhage † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Stoma site hypergranulation † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Thermal burn † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Traumatic haematoma † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Upper limb fracture † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Vaccination complication † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Investigations       
Aspiration bronchial † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Blood urea increased † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Bone density decreased † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Carnitine decreased † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Enterobacter test positive † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Full blood count increased † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Heart rate increased † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Oxygen saturation decreased † 1  0/7 (0.00%)  2/14 (14.29%)  1/6 (16.67%) 
Pco2 increased † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Urine output decreased † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Urine output increased † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Weight decreased † 1  0/7 (0.00%)  2/14 (14.29%)  1/6 (16.67%) 
Weight increased † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
White blood cell count increased † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Dehydration † 1  0/7 (0.00%)  3/14 (21.43%)  0/6 (0.00%) 
Failure to thrive † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Feeding disorder † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Hyperchloraemia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Hyperglycaemia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Hypernatraemia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Hypochloraemia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Hypoglycaemia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Hypokalaemia † 1  1/7 (14.29%)  1/14 (7.14%)  0/6 (0.00%) 
Hyponatraemia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Hypophagia † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Metabolic acidosis † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Weight gain poor † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Back pain † 1  0/7 (0.00%)  2/14 (14.29%)  1/6 (16.67%) 
Hip deformity † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Joint contracture † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Joint hyperextension † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Muscle spasms † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Muscle tightness † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Musculoskeletal pain † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Musculoskeletal stiffness † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Myalgia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Osteopenia † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Pain in extremity † 1  0/7 (0.00%)  6/14 (42.86%)  2/6 (33.33%) 
Scoliosis † 1  0/7 (0.00%)  4/14 (28.57%)  0/6 (0.00%) 
Spinal pain † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Tendinous contracture † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Torticollis † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Nervous system disorders       
Cranial nerve disorder † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Dysarthria † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Headache † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Product Issues       
Device extrusion † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Psychiatric disorders       
Dysphemia † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Intermittent explosive disorder † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Irritability † 1  1/7 (14.29%)  1/14 (7.14%)  0/6 (0.00%) 
Renal and urinary disorders       
Acute kidney injury † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Urinary retention † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Reproductive system and breast disorders       
Penile adhesion † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Aspiration † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Atelectasis † 1  0/7 (0.00%)  2/14 (14.29%)  1/6 (16.67%) 
Bronchial secretion retention † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Chronic respiratory failure † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Cough † 1  1/7 (14.29%)  11/14 (78.57%)  3/6 (50.00%) 
Dysphonia † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Dyspnoea † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Epistaxis † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Hypoventilation † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Hypoxia † 1  2/7 (28.57%)  3/14 (21.43%)  0/6 (0.00%) 
Increased bronchial secretion † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Larynx irritation † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Lower respiratory tract congestion † 1  0/7 (0.00%)  1/14 (7.14%)  2/6 (33.33%) 
Nasal congestion † 1  0/7 (0.00%)  6/14 (42.86%)  2/6 (33.33%) 
Oropharyngeal pain † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Pneumonia aspiration † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Productive cough † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Pulmonary congestion † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Restrictive pulmonary disease † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Rhinitis allergic † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Rhinorrhoea † 1  0/7 (0.00%)  6/14 (42.86%)  1/6 (16.67%) 
Sinus congestion † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
Sleep apnoea syndrome † 1  1/7 (14.29%)  1/14 (7.14%)  0/6 (0.00%) 
Tachypnoea † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Tonsillar hypertrophy † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Upper respiratory tract congestion † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Upper-airway cough syndrome † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Use of accessory respiratory muscles † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders       
Decubitus ulcer † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Dermatitis contact † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Dermatitis diaper † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Dry skin † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Erythema † 1  2/7 (28.57%)  1/14 (7.14%)  0/6 (0.00%) 
Miliaria † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Petechiae † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Rash † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Rash erythematous † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Rash generalised † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Rash macular † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Rash papular † 1  0/7 (0.00%)  1/14 (7.14%)  0/6 (0.00%) 
Skin irritation † 1  1/7 (14.29%)  1/14 (7.14%)  0/6 (0.00%) 
Urticaria † 1  0/7 (0.00%)  2/14 (14.29%)  0/6 (0.00%) 
Vascular disorders       
Flushing † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Haematoma † 1  0/7 (0.00%)  1/14 (7.14%)  1/6 (16.67%) 
Hypertension † 1  1/7 (14.29%)  0/14 (0.00%)  0/6 (0.00%) 
Hypotension † 1  0/7 (0.00%)  0/14 (0.00%)  1/6 (16.67%) 
1
Term from vocabulary, MedDRA 20.0
†
Indicates events were collected by systematic assessment
Despite the early termination of both Parts of the study, the data from this study is of quality and reliable.
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
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Name/Title: Biogen Study Medical Director
Organization: Biogen
Phone: 866-633-4636
EMail: clinicaltrials@biogen.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02462759    
Other Study ID Numbers: 232SM202
2014-003657-33 ( EudraCT Number )
First Submitted: May 14, 2015
First Posted: June 4, 2015
Results First Submitted: September 24, 2019
Results First Posted: January 27, 2020
Last Update Posted: February 17, 2021