Trial Outcomes & Findings for Comparing Risk and Severity of IRRs in Patients Premedicated With Cetirizine vs. Diphenhydramine Prior to Ocrelizumab (NCT NCT04175834)
NCT ID: NCT04175834
Last Updated: 2024-03-04
Results Overview
The proportion of patients having an infusion-related reaction (IRR), as defined by Common Terminology Criteria (CTCAE), version 4 during or after the first-half dose of the first infusion on day 0. IRRs are documented at the infusion clinic on the day of infusion and reported by the patient at the follow-up phone call the next business day after the infusion.
COMPLETED
PHASE3
19 participants
During or after the first-half dose of the first infusion on day 0
2024-03-04
Participant Flow
Adult patients with relapsing or progressive multiple sclerosis (MS), starting ocrelizumab (OCR)
Participant milestones
| Measure |
Diphenhydramine
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
10
|
|
Overall Study
COMPLETED
|
8
|
10
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Diphenhydramine
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Comparing Risk and Severity of IRRs in Patients Premedicated With Cetirizine vs. Diphenhydramine Prior to Ocrelizumab
Baseline characteristics by cohort
| Measure |
Diphenhydramine
n=9 Participants
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 Participants
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
MS Type
Primary Progressive Multiple Sclerosis (PPMS)
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
34.8 years
STANDARD_DEVIATION 12.3 • n=5 Participants
|
37.4 years
STANDARD_DEVIATION 9.40 • n=7 Participants
|
36.2 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Age at MS symptoms onset
|
33.9 years
n=5 Participants
|
33.7 years
n=7 Participants
|
33.9 years
n=5 Participants
|
|
Age at MS diagnosis
|
36.7 years
n=5 Participants
|
34.5 years
n=7 Participants
|
34.6 years
n=5 Participants
|
|
From MS symptoms onset to MS Diagnosis
|
8.6 weeks
n=5 Participants
|
7.4 weeks
n=7 Participants
|
8.6 weeks
n=5 Participants
|
|
Age at OCR start
|
46.3 years
n=5 Participants
|
48.2 years
n=7 Participants
|
47.5 years
n=5 Participants
|
|
Education
High School
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Education
Trade School
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Education
Associate's Degree
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Education
Bachelor's Degree
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Education
Graduate School
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Employment
Disabled
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Employment
Full-time
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Employment
Not working
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Employment
Retired
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
MS Type
Secondary Progressive Mutiple Sclerosis (SPMS)
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Reason start OCR
Breakthrough disease activity on previous treatment
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Reason start OCR
Convenience
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Reason start OCR
First-line therapy
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Reason start OCR
Risk reduction from prior treatment
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Reason start OCR
Side effects of prior treatment
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
MS Type
Relapsing-Remitting Multiple Sclerosis (RRMS)
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: During or after the first-half dose of the first infusion on day 0The proportion of patients having an infusion-related reaction (IRR), as defined by Common Terminology Criteria (CTCAE), version 4 during or after the first-half dose of the first infusion on day 0. IRRs are documented at the infusion clinic on the day of infusion and reported by the patient at the follow-up phone call the next business day after the infusion.
Outcome measures
| Measure |
Diphenhydramine
n=9 Participants
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 Participants
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Proportion of Participants With Infusion-related Reaction (IRR) on Day 0
|
5 participnats
|
6 participnats
|
SECONDARY outcome
Timeframe: during or after receiving the second half dose infusion on day 14.The proportion of patients having an infusion-related reaction as defined by Common Terminology Criteria (CTCAE), version 4 during or after receiving the second half dose infusion on day 14
Outcome measures
| Measure |
Diphenhydramine
n=9 Participants
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 Participants
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Proportion of Participants With Infusion-related Reaction (IRR) on Day 14
|
6 participants
|
8 participants
|
SECONDARY outcome
Timeframe: during or after receiving the first full 600mg dose infusion on day 168.The proportion of patients having an infusion-related reaction as defined by Common Terminology Criteria (CTCAE), version 4 during or after receiving the first full 600mg dose infusion on week 168
Outcome measures
| Measure |
Diphenhydramine
n=9 Participants
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 Participants
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Proportion of Participants With an Infusion-related Reaction (IRR) on Day 168
|
7 participants
|
8 participants
|
SECONDARY outcome
Timeframe: After the infusions on day 0, day 14, and day 168.Patient reported outcome on Treatment Satisfaction Questionnaire for Medication. TSQM is administered within 2 hours after ocrelizumab (OCR) infusion, may be completed via phone to assess patient treatment satisfaction for the infusion. TSQM covers four domains: Global satisfaction, Effectiveness, Side effects, and Convenience. The scores are calculated for each of the subscales, ranging from 0 to 100. Higher score indicates higher satisfaction of the participant with the treatment and lower score indicates lower satisfaction of the participant with the treatment.
Outcome measures
| Measure |
Diphenhydramine
n=9 Participants
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 Participants
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Global Satisfaction- Day 0
|
88.0 score on a scale
Standard Deviation 15.7
|
90.8 score on a scale
Standard Deviation 9.99
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Effectiveness- Day 0
|
78.7 score on a scale
Standard Deviation 18.2
|
86.7 score on a scale
Standard Deviation 11.2
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Side Effects- Day 0
|
94.4 score on a scale
Standard Deviation 11.0
|
100 score on a scale
Standard Deviation 0
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Convenience- Day 0
|
87.6 score on a scale
Standard Deviation 13.9
|
96.1 score on a scale
Standard Deviation 5.89
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Global Satisfaction- Day 14
|
88.6 score on a scale
Standard Deviation 14.7
|
93.3 score on a scale
Standard Deviation 11.7
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Effectiveness- Day 14
|
78.1 score on a scale
Standard Deviation 14.0
|
91.9 score on a scale
Standard Deviation 14.2
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Side Effects- Day 14
|
92.7 score on a scale
Standard Deviation 10.4
|
100 score on a scale
Standard Deviation 0
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Convenience- Day 14
|
90.3 score on a scale
Standard Deviation 11.0
|
96.6 score on a scale
Standard Deviation 7.33
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Global Satisfaction- Day 168
|
91.7 score on a scale
Standard Deviation 13.9
|
99.1 score on a scale
Standard Deviation 2.67
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Effectiveness- Day 168
|
87.5 score on a scale
Standard Deviation 15.6
|
93.5 score on a scale
Standard Deviation 10.0
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Side Effects- day 168
|
95.8 score on a scale
Standard Deviation 6.98
|
96.3 score on a scale
Standard Deviation 11.0
|
|
Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
Convenience- Day 168
|
94.4 score on a scale
Standard Deviation 7.04
|
95.7 score on a scale
Standard Deviation 10.9
|
SECONDARY outcome
Timeframe: after the infusions on day 0, day 14, and day 168.Patient reported outcome on Stanford Sleepiness Score (SSS) administered prior to starting and within 2 hours after ocrelizumab (OCR) infusion, may be completed via phone. SSS measures sleepiness at specific times in a day. Participants will use a scale from 1 to 7 best representing their level of perceived sleepiness. The higher the score, the sleepier the subject and a lower score indicates the alertness of the subject.
Outcome measures
| Measure |
Diphenhydramine
n=9 Participants
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 Participants
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Stanford Sleepiness Scale (SSS) Score on Days 0, 14, and 168
Day 0
|
3.11 score on a scale
Standard Deviation 1.27
|
1.90 score on a scale
Standard Deviation 0.876
|
|
Stanford Sleepiness Scale (SSS) Score on Days 0, 14, and 168
Day 14
|
3.13 score on a scale
Standard Deviation 1.13
|
2.00 score on a scale
Standard Deviation 0.667
|
|
Stanford Sleepiness Scale (SSS) Score on Days 0, 14, and 168
Day 168
|
2.50 score on a scale
Standard Deviation 0.837
|
2.33 score on a scale
Standard Deviation 1.00
|
SECONDARY outcome
Timeframe: after the infusions on day 0, day 14, and day 168.Patient reported outcomes on Visual Analog Scale for Fatigue, administered prior to starting and within 2 hours after ocrelizumab (OCR) infusion, may be completed via phone. The scale consists of various items relating to the participants' experience of fatigue and energy. Fatigue subscale ranges from 0-10 and a higher the score represents a greater fatigue for the participant. Energy subscale ranges from 0-10 and a higher the score represents a greater energy as perceived by the participant.
Outcome measures
| Measure |
Diphenhydramine
n=9 Participants
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 Participants
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Visual Analog Scale for Fatigue (VAS-F) Score on Days 0, 14 and 168
Fatigue- Day 0
|
4.10 score on a scale
Standard Deviation 2.19
|
1.92 score on a scale
Standard Deviation 2.13
|
|
Visual Analog Scale for Fatigue (VAS-F) Score on Days 0, 14 and 168
Energy at Day 0
|
5.20 score on a scale
Standard Deviation 1.35
|
6.28 score on a scale
Standard Deviation 2.56
|
|
Visual Analog Scale for Fatigue (VAS-F) Score on Days 0, 14 and 168
Fatigue- Day 14
|
3.95 score on a scale
Standard Deviation 1.94
|
1.94 score on a scale
Standard Deviation 1.12
|
|
Visual Analog Scale for Fatigue (VAS-F) Score on Days 0, 14 and 168
Energy- Day 14
|
4.63 score on a scale
Standard Deviation 1.98
|
6.08 score on a scale
Standard Deviation 1.80
|
|
Visual Analog Scale for Fatigue (VAS-F) Score on Days 0, 14 and 168
Fatigue- Day 168
|
3.52 score on a scale
Standard Deviation 1.08
|
2.12 score on a scale
Standard Deviation 2.12
|
|
Visual Analog Scale for Fatigue (VAS-F) Score on Days 0, 14 and 168
Energy- Day 168
|
5.33 score on a scale
Standard Deviation 2.66
|
5.82 score on a scale
Standard Deviation 2.43
|
SECONDARY outcome
Timeframe: at day 168.Modified Fatigue Impact Scale (MFIS) administered after the 2nd dose of OCR. Subject answers 21 questions (9 physical, 10 cognitive, and 2 psychological items) related to fatigue in the past 4 weeks with choices of frequency: 0: Never, 1: Rarely, 2: Sometimes, 3: Often, or 4: Almost always. The total MFIS score ranges from 0 to 84. A higher total score represents greater fatigue as perceived by the participants.
Outcome measures
| Measure |
Diphenhydramine
n=8 Participants
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 Participants
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Modified Fatigue Impact Scale (MFIS) Score on Day 168
|
23.9 score on a scale
Standard Deviation 15.9
|
18.3 score on a scale
Standard Deviation 22.2
|
SECONDARY outcome
Timeframe: at day 168.Multiple Sclerosis Impact Scale (MSIS-29) is administered after the 2nd dose of ocrelizumab (OCR) infusion to evaluate the physical and psychological impact of multiple sclerosis (MS). Participants rate their symptoms related to MS as 1-Not at all, 2-a little 3-Moderately or 4-Extremely on the two subscales, 20-item physical subscale and 9-item psychological subscale. The two subscales are scored by summing the responses across items, then converting to a 0-100 scale using a formula. For both subscales, higher scores indicate higher impact of MS or greater disability for the participant. Formula for physical impact subscale score: (100\*(observed score-20))/ (100-20) Formula for psychological impact subscale score: (100\*(observed score 9))/ (45-9)
Outcome measures
| Measure |
Diphenhydramine
n=8 Participants
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 Participants
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Multiple Sclerosis Impact Scale (MSIS-29) Score on Day168
Physical Subscale
|
19.7 score on a scale
Standard Deviation 25.7
|
6.38 score on a scale
Standard Deviation 9.31
|
|
Multiple Sclerosis Impact Scale (MSIS-29) Score on Day168
Psychological Subscale
|
13.0 score on a scale
Standard Deviation 10.2
|
12.3 score on a scale
Standard Deviation 14.1
|
Adverse Events
Diphenhydramine
Cetirizine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Diphenhydramine
n=9 participants at risk
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
Cetirizine
n=10 participants at risk
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
|
|---|---|---|
|
Immune system disorders
Infusion-related reaction
|
77.8%
7/9 • The period during which all adverse events and serious adverse events collected began after the informed consent is obtained and ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier, up to 28 weeks.
|
80.0%
8/10 • The period during which all adverse events and serious adverse events collected began after the informed consent is obtained and ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier, up to 28 weeks.
|
Additional Information
Chiayi Chen, Director of WC/PBSI Clinical Research Program
Providence Health & Services
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place