Trial Outcomes & Findings for Tocilizumab as Add-On Treatment For Residual Positive, Negative, and Cognitive Symptoms of Schizophrenia (NCT NCT02034474)
NCT ID: NCT02034474
Last Updated: 2018-12-26
Results Overview
To evaluate an anticipated clinical response to tocilizumab treatment including positive, negative and cognitive symptoms by the change in the Positive and Negative Syndrome Scale (PANSS) total score. Score ranges from 30 to 210 for PANSS total, 16-112 for General, 7-49 for positive and 7-49 for negative symptoms subscales. A lower score means less symptomatic. There is a total score and general psychopathology scores, a positive symptoms score and a negative symptom score. The unit of measure is units on a scale from 1-7, whole numbers only. Summed scores are simply added to each other
COMPLETED
PHASE4
59 participants
Baseline (start of tocilizumab) through 12 weeks. We present the change scores
2018-12-26
Participant Flow
Of the 59 subjects who signed consent, 22 did not receive study drug. In addition, one of the 37 subjects who received study drug did not participate in any follow up assessments so was not included in the ITT analysis
Participant milestones
| Measure |
Tocilizumab
Tocilizumab (N=19)
|
Placebo
Placebo (N=17)
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
17
|
|
Overall Study
1 Dose
|
2
|
4
|
|
Overall Study
2 Doses
|
2
|
0
|
|
Overall Study
3 Doses
|
15
|
13
|
|
Overall Study
COMPLETED
|
15
|
13
|
|
Overall Study
NOT COMPLETED
|
4
|
4
|
Reasons for withdrawal
| Measure |
Tocilizumab
Tocilizumab (N=19)
|
Placebo
Placebo (N=17)
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
Baseline Characteristics
ITT population
Baseline characteristics by cohort
| Measure |
Placebo
n=17 Participants
Placebo-receiving group
|
Tocilizumab
n=19 Participants
Tocilizumab-receiving group
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=17 Participants • ITT population
|
0 Participants
n=19 Participants • ITT population
|
0 Participants
n=36 Participants • ITT population
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=17 Participants • ITT population
|
19 Participants
n=19 Participants • ITT population
|
36 Participants
n=36 Participants • ITT population
|
|
Age, Categorical
>=65 years
|
0 Participants
n=17 Participants • ITT population
|
0 Participants
n=19 Participants • ITT population
|
0 Participants
n=36 Participants • ITT population
|
|
Age, Continuous
|
41.67 yrs
STANDARD_DEVIATION 10.25 • n=17 Participants • ITT Population
|
43.24 yrs
STANDARD_DEVIATION 11.42 • n=19 Participants • ITT Population
|
42.50 yrs
STANDARD_DEVIATION 10.76 • n=36 Participants • ITT Population
|
|
Sex: Female, Male
Female
|
4 Participants
n=17 Participants • ITT Population
|
7 Participants
n=19 Participants • ITT Population
|
11 Participants
n=36 Participants • ITT Population
|
|
Sex: Female, Male
Male
|
13 Participants
n=17 Participants • ITT Population
|
12 Participants
n=19 Participants • ITT Population
|
25 Participants
n=36 Participants • ITT Population
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=17 Participants • ITT Population
|
5 Participants
n=19 Participants • ITT Population
|
6 Participants
n=36 Participants • ITT Population
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=17 Participants • ITT Population
|
14 Participants
n=19 Participants • ITT Population
|
30 Participants
n=36 Participants • ITT Population
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=17 Participants • ITT Population
|
0 Participants
n=19 Participants • ITT Population
|
0 Participants
n=36 Participants • ITT Population
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=17 Participants • ITT Population
|
0 Participants
n=19 Participants • ITT Population
|
0 Participants
n=36 Participants • ITT Population
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=17 Participants • ITT Population
|
0 Participants
n=19 Participants • ITT Population
|
1 Participants
n=36 Participants • ITT Population
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=17 Participants • ITT Population
|
0 Participants
n=19 Participants • ITT Population
|
0 Participants
n=36 Participants • ITT Population
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=17 Participants • ITT Population
|
12 Participants
n=19 Participants • ITT Population
|
18 Participants
n=36 Participants • ITT Population
|
|
Race (NIH/OMB)
White
|
9 Participants
n=17 Participants • ITT Population
|
5 Participants
n=19 Participants • ITT Population
|
14 Participants
n=36 Participants • ITT Population
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=17 Participants • ITT Population
|
2 Participants
n=19 Participants • ITT Population
|
3 Participants
n=36 Participants • ITT Population
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=17 Participants • ITT Population
|
0 Participants
n=19 Participants • ITT Population
|
0 Participants
n=36 Participants • ITT Population
|
|
Region of Enrollment
United States
|
17 Participants
n=17 Participants • ITT Population
|
19 Participants
n=19 Participants • ITT Population
|
36 Participants
n=36 Participants • ITT Population
|
|
PANSS Total
|
73.94 panss score
STANDARD_DEVIATION 15.52 • n=17 Participants
|
70.68 panss score
STANDARD_DEVIATION 11.2 • n=19 Participants
|
72.22 panss score
STANDARD_DEVIATION 14.24 • n=36 Participants
|
|
Smoker
|
7 Participants
n=17 Participants
|
8 Participants
n=19 Participants
|
15 Participants
n=36 Participants
|
|
cigs /day
|
8 cigarettes per day
STANDARD_DEVIATION 3 • n=17 Participants
|
10 cigarettes per day
STANDARD_DEVIATION 5 • n=19 Participants
|
9 cigarettes per day
STANDARD_DEVIATION 4 • n=36 Participants
|
|
chlorpromazine equivalents
|
377 milligrams
STANDARD_DEVIATION 346 • n=12 Participants • Some participants did not provide antipsychotic dosage information to be converted to chlorpromazine equivalent
|
257 milligrams
STANDARD_DEVIATION 192 • n=5 Participants • Some participants did not provide antipsychotic dosage information to be converted to chlorpromazine equivalent
|
310 milligrams
STANDARD_DEVIATION 396 • n=17 Participants • Some participants did not provide antipsychotic dosage information to be converted to chlorpromazine equivalent
|
|
weight
|
203.24 pounds
STANDARD_DEVIATION 51.95 • n=17 Participants
|
218.63 pounds
STANDARD_DEVIATION 45.24 • n=19 Participants
|
211.36 pounds
STANDARD_DEVIATION 44.01 • n=36 Participants
|
|
Clinical Global Impression - Severity Scale
|
4 units on a scale
STANDARD_DEVIATION 0.4 • n=17 Participants
|
4 units on a scale
STANDARD_DEVIATION 0.3 • n=19 Participants
|
4 units on a scale
STANDARD_DEVIATION 0.5 • n=36 Participants
|
PRIMARY outcome
Timeframe: Baseline (start of tocilizumab) through 12 weeks. We present the change scoresPopulation: 17 placebo patients and 19 tocilizumab patients were included in the ITT analysis
To evaluate an anticipated clinical response to tocilizumab treatment including positive, negative and cognitive symptoms by the change in the Positive and Negative Syndrome Scale (PANSS) total score. Score ranges from 30 to 210 for PANSS total, 16-112 for General, 7-49 for positive and 7-49 for negative symptoms subscales. A lower score means less symptomatic. There is a total score and general psychopathology scores, a positive symptoms score and a negative symptom score. The unit of measure is units on a scale from 1-7, whole numbers only. Summed scores are simply added to each other
Outcome measures
| Measure |
Placebo
n=17 Participants
Patients on placebo
|
Tocilizumab
n=19 Participants
Patients on Tocilizumab
|
|---|---|---|
|
Clinical Response to Tocilizumab
|
-5.33 Units on a scale (PANSS)
Standard Deviation 17.96
|
-0.5 Units on a scale (PANSS)
Standard Deviation 12.62
|
SECONDARY outcome
Timeframe: Baseline (start of tocilizumab) through 12 weeksPopulation: These subjects were included in the ITT analysis and received the MATRICS. We will present total composite change scores from baseline to week 12
MATRICS cognitive consensus battery, overall t score change. The composite T-score at each time point (baseline and week 12) is a T-Score (ranging from 0 to 100) reflecting overall neuropsychological function, aggregated from the participant's T-scores on the MATRICS subscales for Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social Cognition. The outcome is the difference between overall composite T-score at baseline and week 12, with higher difference score reflecting a greater improvement in neuropsychological performance.
Outcome measures
| Measure |
Placebo
n=17 Participants
Patients on placebo
|
Tocilizumab
n=19 Participants
Patients on Tocilizumab
|
|---|---|---|
|
Cognitive Symptomatology - Overall MATRICS t Score Change
|
2.83 T Score Difference
Standard Deviation 5.59
|
1.47 T Score Difference
Standard Deviation 8.53
|
SECONDARY outcome
Timeframe: Baseline (start of tocilizumab) through 12 weeksPopulation: These subjects were included in the ITT analysis and received the UPSA at both baseline and week 12.We will present total composite change scores from baseline to week 12
At Baseline and Week 12, participants are UPSA-B given items reflecting ability to complete tasks encountered in daily life, across two domains, Financial Skills and Communication Skills. % correct is calculated for each domain and converted to a standardized score from 0-50. These scores are summed to produce a total summary score ranging from 0-100. The outcome is the difference between this summary score at Baseline and Week 12, with a higher difference score reflecting a greater increase in functional capacity.
Outcome measures
| Measure |
Placebo
n=16 Participants
Patients on placebo
|
Tocilizumab
n=12 Participants
Patients on Tocilizumab
|
|---|---|---|
|
Cognitive Symptomatology - UPSA-B Score Change
|
1.12 Change in score on a scale
Standard Deviation 0.23
|
1.12 Change in score on a scale
Standard Deviation 0.17
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline (start of tocilizumab) through 12 weeksComparison of cytokines, in particular IL-6 levels and the positive, negative and cognitive symptoms and impairments in daily functioning in schizophrenia. These outcomes will be measured by Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Clinical Global Impression (CGI), University of California Performance Skills Assessments (UPSA) and MATRICS.
Outcome measures
Outcome data not reported
Adverse Events
Placebo
Tocilizumab
Serious adverse events
| Measure |
Placebo
n=17 participants at risk
Subjects who received placebo
|
Tocilizumab
n=19 participants at risk
Subjects who received tocilizumab
|
|---|---|---|
|
Blood and lymphatic system disorders
agranulocytosis
|
0.00%
0/17 • 3 years
|
5.3%
1/19 • Number of events 1 • 3 years
|
Other adverse events
| Measure |
Placebo
n=17 participants at risk
Subjects who received placebo
|
Tocilizumab
n=19 participants at risk
Subjects who received tocilizumab
|
|---|---|---|
|
Nervous system disorders
Inpatient admission
|
5.9%
1/17 • Number of events 1 • 3 years
|
5.3%
1/19 • Number of events 1 • 3 years
|
|
Blood and lymphatic system disorders
Low ANC
|
11.8%
2/17 • Number of events 2 • 3 years
|
10.5%
2/19 • Number of events 2 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
URI
|
5.9%
1/17 • Number of events 1 • 3 years
|
0.00%
0/19 • 3 years
|
|
Infections and infestations
Tooth infection
|
5.9%
1/17 • Number of events 1 • 3 years
|
0.00%
0/19 • 3 years
|
|
Gastrointestinal disorders
nausea
|
0.00%
0/17 • 3 years
|
5.3%
1/19 • Number of events 1 • 3 years
|
|
General disorders
fatigue
|
0.00%
0/17 • 3 years
|
5.3%
1/19 • Number of events 1 • 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place