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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants With Early Manifest Huntington's Disease

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ClinicalTrials.gov Identifier: NCT02519036
Recruitment Status : Completed
First Posted : August 10, 2015
Results First Posted : May 31, 2019
Last Update Posted : May 31, 2019
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Huntington's Disease
Interventions Drug: ISIS 443139 10 mg
Drug: ISIS 443139 30 mg
Drug: ISIS 443139 60 mg
Drug: ISIS 443139 90 mg
Drug: ISIS 443139 120 mg
Other: Placebo
Enrollment 46
Recruitment Details 46 participants were enrolled in the United Kingdom, Canada and Germany.
Pre-assignment Details  
Arm/Group Title Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Period Title: Overall Study
Started 12 3 6 6 9 10
Completed 12 3 6 6 9 10
Not Completed 0 0 0 0 0 0
Arm/Group Title Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg Total
Hide Arm/Group Description Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Total of all reporting groups
Overall Number of Baseline Participants 12 3 6 6 9 10 46
Hide Baseline Analysis Population Description
Safety set included all participants who were randomized and received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 3 participants 6 participants 6 participants 9 participants 10 participants 46 participants
49  (10) 44  (17) 53  (7) 43  (11) 46  (10) 45  (10) 47  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 3 participants 6 participants 6 participants 9 participants 10 participants 46 participants
Female
4
  33.3%
1
  33.3%
1
  16.7%
3
  50.0%
3
  33.3%
6
  60.0%
18
  39.1%
Male
8
  66.7%
2
  66.7%
5
  83.3%
3
  50.0%
6
  66.7%
4
  40.0%
28
  60.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 12 participants 3 participants 6 participants 6 participants 9 participants 10 participants 46 participants
White
11
  91.7%
3
 100.0%
5
  83.3%
6
 100.0%
9
 100.0%
9
  90.0%
43
  93.5%
Black
1
   8.3%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
2
   4.3%
Other Race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
1
   2.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Not Hispanic or Latino Number Analyzed 12 participants 3 participants 6 participants 6 participants 9 participants 10 participants 46 participants
12
 100.0%
3
 100.0%
6
 100.0%
6
 100.0%
9
 100.0%
10
 100.0%
46
 100.0%
1.Primary Outcome
Title Number of Participants With Treatment-related Adverse Events (TEAEs)
Hide Description An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of Study Drug and subsequently worsened or was not present prior to receiving the first dose of Study Drug but subsequently appeared.
Time Frame Up to approximately 28 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included all participants who were randomized and received at least one dose of study drug.
Arm/Group Title Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description:
Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Overall Number of Participants Analyzed 12 3 6 6 9 10
Measure Type: Count of Participants
Unit of Measure: Participants
12
 100.0%
3
 100.0%
6
 100.0%
6
 100.0%
9
 100.0%
9
  90.0%
2.Secondary Outcome
Title Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139
Hide Description [Not Specified]
Time Frame Days 1, 29, 57, 85, and 113 or 141
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population included all participants who were randomized to ISIS 443139, received at least one dose and had sufficient sampling to permit PK evaluation.
Arm/Group Title ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description:
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Overall Number of Participants Analyzed 3 6 6 9 10
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
Day 1 Number Analyzed 3 participants 6 participants 6 participants 9 participants 10 participants
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Day 29 Number Analyzed 3 participants 6 participants 6 participants 9 participants 10 participants
NA [1]   (NA) NA [1]   (NA) 1.77  (1.61) 1.55  (1.06) 2.06  (1.01)
Day 57 Number Analyzed 3 participants 6 participants 6 participants 9 participants 10 participants
NA [1]   (NA) 1.69  (0.530) 2.77  (2.04) 2.36  (1.34) 2.40  (1.24)
Day 85 Number Analyzed 3 participants 6 participants 6 participants 9 participants 10 participants
NA [1]   (NA) 1.96  (1.22) 2.88  (2.54) 2.05  (1.25) 2.53  (0.628)
Day 113 Number Analyzed 3 participants 3 participants 3 participants 5 participants 5 participants
NA [1]   (NA) 1.63  (0.250) 1.84  (1.71) 2.28  (0.438) 2.70  (1.20)
Day 141 Number Analyzed 0 participants 3 participants 3 participants 4 participants 5 participants
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
'NA' signifies that the values were below the lower limit of quantitation.
3.Other Pre-specified Outcome
Title Maximum Plasma Concentration (Cmax) for ISIS 443139
Hide Description [Not Specified]
Time Frame Days 1 and 85
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants who were randomized to ISIS 443139, received at least one dose and had sufficient sampling to permit PK evaluation.
Arm/Group Title ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description:
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Overall Number of Participants Analyzed 3 6 6 9 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Day 1
74.0
(24.3%)
203
(81.9%)
500
(39.0%)
600
(94.9%)
717
(69.2%)
Day 85
124
(73.6%)
179
(55.1%)
396
(77.2%)
439
(86.0%)
731
(90.6%)
4.Other Pre-specified Outcome
Title Time to Maximum Plasma Concentration (Tmax) for ISIS 443139
Hide Description [Not Specified]
Time Frame Days 1 and 85
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants who were randomized to ISIS 443139, received at least one dose and had sufficient sampling to permit PK evaluation.
Arm/Group Title ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description:
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Overall Number of Participants Analyzed 3 6 6 9 10
Median (Full Range)
Unit of Measure: hour (h)
Day 1
3.03
(2.05 to 5.95)
3.03
(2.00 to 4.00)
1.99
(0.533 to 3.08)
3.05
(2.00 to 8.02)
4.00
(2.00 to 23.8)
Day 85
2.02
(0.717 to 3.02)
2.03
(0.550 to 3.07)
2.02
(1.00 to 4.02)
3.02
(0.600 to 5.02)
4.03
(2.00 to 23.9)
5.Other Pre-specified Outcome
Title Change From Baseline in CSF Mutant Huntingtin (fM) Protein Concentration
Hide Description Baseline was defined as the last non-missing measure prior to the first dose.
Time Frame Baseline to Final Assessment (Day 85 or 113)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set included all participants who were randomized and received all doses of the protocol-specified study drug.
Arm/Group Title Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description:
Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Overall Number of Participants Analyzed 12 3 6 6 9 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
Baseline 109.13  (42.57) 143.65  (49.74) 119.83  (45.27) 116.70  (30.46) 104.99  (65.01) 95.87  (35.11)
Change from Baseline 4.08  (28.47) -31.28  (25.71) -31.98  (24.96) -30.83  (17.17) -45.76  (27.65) -38.41  (21.59)
6.Other Pre-specified Outcome
Title Change From Baseline in CSF Neurofilament Light Chain Concentration
Hide Description Baseline was defined as the last non-missing measure prior to the first dose.
Time Frame Baseline to Final Assessment (Day 85 or 113)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set included all participants who were randomized and received all doses of the protocol-specified study drug.
Arm/Group Title Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description:
Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Overall Number of Participants Analyzed 12 3 6 6 9 10
Mean (Standard Deviation)
Unit of Measure: nanograms per liter (ng/L)
Baseline 2774  (767) 2697  (1909) 2548  (916) 2280  (976) 2328  (951) 2551  (872)
Change from Baseline 324  (371) 77  (223) 202  (493) 274  (301) 1161  (2980) 628  (1128)
7.Other Pre-specified Outcome
Title Ventricular Volume as Assessed by Structural Magnetic Resonance Imaging (MRI)
Hide Description [Not Specified]
Time Frame Screening, Days 113, and 197
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set included all participants who were randomized and received all doses of the protocol-specified study drug.
Arm/Group Title Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description:
Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Overall Number of Participants Analyzed 12 3 6 6 9 10
Mean (Standard Deviation)
Unit of Measure: mL
Screening 35.58  (19.02) 17.88  (12.20) 33.02  (17.46) 31.90  (13.21) 39.33  (23.52) 27.53  (19.31)
Day 113 36.11  (19.37) 18.66  (12.84) 33.56  (17.87) 32.04  (14.26) 42.24  (25.80) 30.36  (21.80)
Day 197 36.46  (18.97) 19.69  (13.03) 34.82  (18.16) 34.57  (14.82) 44.43  (27.37) 33.02  (24.61)
8.Other Pre-specified Outcome
Title Huntington's Disease (HD) Cognitive Assessment Battery Composite Score
Hide Description The HD Cognitive Battery was developed as a means of measuring cognitive dysfunction in late premanifest and early manifest HD patients. The 6 tests that comprise the battery were selected based on test sensitivity, practice effects, reliability, domain coverage, feasibility for use in clinical trials, and tolerability. A composite cognitive score was calculated by the average z-score of the 6 individual tests. A positive change from baseline indicated improvement in cognitive function; a negative change indicated worsening. Baseline was defined as the last non-missing measure prior to the first dose.
Time Frame Baseline to Days 84, 141, and 197
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set included all participants who were randomized and received all doses of the protocol-specified study drug.
Arm/Group Title Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description:
Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Overall Number of Participants Analyzed 12 3 6 6 9 10
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 12 participants 3 participants 6 participants 6 participants 9 participants 10 participants
-0.0860  (0.2941) 0.2979  (0.5157) 0.0839  (0.5108) -0.0404  (0.3976) -0.1483  (0.3284) 0.1212  (0.3877)
Change at Day 84 Number Analyzed 12 participants 3 participants 6 participants 6 participants 9 participants 10 participants
-0.0403  (0.2261) 0.1314  (0.3670) -0.0430  (0.3585) -0.0338  (0.2756) 0.1297  (0.2560) -0.0920  (0.1668)
Change at Day 141 Number Analyzed 12 participants 3 participants 6 participants 6 participants 9 participants 8 participants
0.0432  (0.1829) 0.4441  (0.8487) -0.1065  (0.2112) -0.1792  (0.2298) 0.2194  (0.2224) -0.0547  (0.2136)
Change at Day 197 Number Analyzed 11 participants 3 participants 6 participants 5 participants 7 participants 10 participants
-0.0778  (0.2881) 0.4202  (1.0482) -0.0469  (0.3151) -0.1633  (0.1170) 0.0827  (0.2897) -0.1387  (0.2717)
Time Frame Up to approximately 28 weeks
Adverse Event Reporting Description Safety set included all participants who were randomized and received at least one dose of study drug.
 
Arm/Group Title Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Hide Arm/Group Description Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period. Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
All-Cause Mortality
Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/3 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/9 (0.00%)   0/10 (0.00%) 
Hide Serious Adverse Events
Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/12 (8.33%)   0/3 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/9 (0.00%)   0/10 (0.00%) 
Injury, poisoning and procedural complications             
Post lumbar puncture syndrome † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
1
Term from vocabulary, MedDRA (18.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo ISIS 443139 10 mg ISIS 443139 30 mg ISIS 443139 60 mg ISIS 443139 90 mg ISIS 443139 120 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   3/3 (100.00%)   6/6 (100.00%)   6/6 (100.00%)   9/9 (100.00%)   9/10 (90.00%) 
Blood and lymphatic system disorders             
Lymphadenopathy † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Cardiac disorders             
Bundle branch block right † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Ventricular extrasystoles † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Ear and labyrinth disorders             
Ear pain † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Eye disorders             
Ocular discomfort † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Vision blurred † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Gastrointestinal disorders             
Diarrhoea † 1  1/12 (8.33%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Toothache † 1  0/12 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Abdominal pain upper † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Dental caries † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Dyspepsia † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Gastritis † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Nausea † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Vomiting † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
General disorders             
Fatigue † 1 [1]  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  1/9 (11.11%)  2/10 (20.00%) 
Asthenia † 1 [1]  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Chills † 1 [1]  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Discomfort † 1 [1]  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Malaise † 1 [1]  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Peripheral swelling † 1 [1]  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Infections and infestations             
Nasopharyngitis † 1  2/12 (16.67%)  1/3 (33.33%)  0/6 (0.00%)  1/6 (16.67%)  3/9 (33.33%)  2/10 (20.00%) 
Upper respiratory tract infection † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  3/6 (50.00%)  1/9 (11.11%)  0/10 (0.00%) 
Rhinitis † 1  2/12 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/9 (22.22%)  0/10 (0.00%) 
Bronchitis † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/9 (0.00%)  1/10 (10.00%) 
Influenza † 1  0/12 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Rhinovirus infection † 1  0/12 (0.00%)  2/3 (66.67%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Sinusitis † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Urinary tract infection † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Bronchopneumonia † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Conjunctivitis † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Gastrointestinal infection † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Respiratory tract infection † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Viral infection † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Vulvovaginal candidiasis † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Injury, poisoning and procedural complications             
Procedural pain † 1  6/12 (50.00%)  1/3 (33.33%)  1/6 (16.67%)  3/6 (50.00%)  6/9 (66.67%)  8/10 (80.00%) 
Post lumbar puncture syndrome † 1  4/12 (33.33%)  1/3 (33.33%)  2/6 (33.33%)  1/6 (16.67%)  3/9 (33.33%)  5/10 (50.00%) 
Fall † 1  3/12 (25.00%)  0/3 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  2/9 (22.22%)  2/10 (20.00%) 
Skin abrasion † 1  1/12 (8.33%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/9 (22.22%)  2/10 (20.00%) 
Contusion † 1  2/12 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Joint injury † 1  1/12 (8.33%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Laceration † 1  1/12 (8.33%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Head injury † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Ligament sprain † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Muscle injury † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Muscle strain † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Tooth injury † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Upper limb fracture † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Investigations             
Blood creatine phosphokinase increased † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Blood thyroid stimulating hormone increased † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Body temperature increased † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
C-reactive protein increased † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Gamma-glutamyltransferase increased † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Thyroxine increased † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Urine analysis abnormal † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia † 1  2/12 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  2/9 (22.22%)  0/10 (0.00%) 
Back pain † 1  1/12 (8.33%)  0/3 (0.00%)  2/6 (33.33%)  2/6 (33.33%)  0/9 (0.00%)  0/10 (0.00%) 
Musculoskeletal pain † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Pain in extremity † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Coccydynia † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Muscle spasms † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Osteopenia † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Synovial cyst † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Nervous system disorders             
Headache † 1  6/12 (50.00%)  0/3 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  1/9 (11.11%)  3/10 (30.00%) 
Hypoaesthesia † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/9 (11.11%)  1/10 (10.00%) 
Dizziness † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Paraesthesia † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  1/10 (10.00%) 
Tension headache † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Head discomfort † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Neuropathy peripheral † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Pleocytosis † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Syncope † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Psychiatric disorders             
Anxiety † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Insomnia † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Mood altered † 1  0/12 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Reproductive system and breast disorders             
Erectile dysfunction † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Cough † 1  1/12 (8.33%)  0/3 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Epistaxis † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Oropharyngeal pain † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Throat irritation † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Skin and subcutaneous tissue disorders             
Alopecia † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Dermatitis allergic † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Dry skin † 1  1/12 (8.33%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/10 (0.00%) 
Rash † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/10 (10.00%) 
Rash erythematous † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Scab † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/10 (0.00%) 
Skin reaction † 1  0/12 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
Vascular disorders             
Haematoma † 1  0/12 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  0/9 (0.00%)  0/10 (0.00%) 
1
Term from vocabulary, MedDRA (18.0)
†
Indicates events were collected by systematic assessment
[1]
General disorders and administration site conditions
There are no limitations or caveats for this study.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Ionis Pharmaceuticals, Inc.
Organization: Ionis Pharmaceuticals, Inc.
Phone: 800-679-4747
EMail: patients@ionisph.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02519036    
Other Study ID Numbers: ISIS 443139-CS1
2015-000381-66 ( EudraCT Number )
First Submitted: August 1, 2015
First Posted: August 10, 2015
Results First Submitted: May 6, 2019
Results First Posted: May 31, 2019
Last Update Posted: May 31, 2019