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| ID | Type | Description | Link |
|---|---|---|---|
| PRECEPT | Other Identifier | Providence health & Services |
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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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This 6-month randomized controlled pilot study will determine whether there is some evidence that cetirizine is better tolerated than diphenhydramine without an increase in Infusion-Related Reactions (IRRs) in subjects receiving ocrelizumab(OCR) for multiple sclerosis (MS).
Ocrelizumab was approved by the US Food and Drug administration in March 2017 for the indication of Relapsing Remitting Multiple Sclerosis (RRMS) and Primary Progressive Multiple Sclerosis (PPMS). The landmark studies used to gain approval found ocrelizumab (OCR) to be well tolerated, but that at least one Infusion-Related Reaction (IRR) occurred in about one-third of patients. Because of this, neurologists typically prescribe prophylactic premedication with 100mg of methylprednisolone, 1 gram of acetaminophen, and 50 mg of IV diphenhydramine. However, many patients experience extreme sedation that interferes with their lifestyle considerably.
This 6-month randomized controlled pilot study will determine whether there is some evidence that cetirizine is better tolerated than diphenhydramine without an increase in IRRs. Fifty-two patients, 26 patients per arm, will be randomized in a 1:1 ratio to receive cetirizine or diphenhydramine as premedication prior to OCR infusions on day 0 (1st half dose of 300mg), day 14 (2nd half dose of 300mg) and week 24 (1st full dose of 600mg).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| diphenhydramine | Other | 25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion. |
|
| cetirizine | Active Comparator | 10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cetrizine | Drug | prophylaxis |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants With Infusion-related Reaction (IRR) on Day 0 | 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. | During or after the first-half dose of the first infusion on day 0 |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants With Infusion-related Reaction (IRR) 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 | during or after receiving the second half dose infusion on day 14. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kyle Smoot, MD | Providence Health & Services | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Providence Neurological Specialties West | Portland | Oregon | 97225 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. Accessed 02/13/19, 2019. | ||
| Background | Genentech Inc. Ocrevus: Highlights of Prescribing Information. 2018; https://www.gene.com/download/pdf/ocrevus_prescribing.pdf. Accessed 02/13/2019. | ||
| Background | Mylan Pharmaceuticals. cetirizine hydrochloride 10 mg tablet. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bd0dc7f6-5fb9-4381-bd81-b150b75a2c68. Accessed 9/3/2019, 2019. | ||
| Background | Major Pharmaceuticals. diphenhydramine hydrochloride 25mg capsule. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=04e70311-6412-4a20-84e3-f6e26d5f19ab. Accessed 9/3/2019, 2019. | ||
| Background | US Food and Drug Administration. Non-Inferiority Clinical Trials to Establish Effectiveness: Guidance for Industry. 2016. | ||
| 28002679 |
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Adult patients with relapsing or progressive multiple sclerosis (MS), starting ocrelizumab (OCR)
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| ID | Title | Description |
|---|---|---|
| FG000 | Diphenhydramine | 25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion. antihistamine: prophylaxis |
| FG001 | Cetirizine | 10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion. antihistamine: prophylaxis |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Diphenhydramine | 25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion. antihistamine: prophylaxis |
| BG001 | Cetirizine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Participants With Infusion-related Reaction (IRR) on Day 0 | 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. | Posted | Number | participnats | During or after the first-half dose of the first infusion on day 0 |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Diphenhydramine | 25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion. antihistamine: prophylaxis |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infusion-related reaction | Immune system disorders | NCI CTCAE (v5.0) | Systematic Assessment | IRR after the first half of first dose 9300mg) of OCR infusion |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chiayi Chen, Director of WC/PBSI Clinical Research Program | Providence Health & Services | 503-216-1012 | Chiayi.Chen@providence.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 19, 2021 | Aug 2, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| ID | Term |
|---|---|
| D004155 | Diphenhydramine |
| ID | Term |
|---|---|
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D001559 | Benzhydryl Compounds |
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Randomized, controlled, pilot study to determine there is evidence that cetirizine is non-inferior to diphenhydramine in limiting the proportion and severity of infusion related reactions to ocrelizumab infusions.
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| diphenhydramine | Drug | prophylaxis |
|
|
| Proportion of Participants With an Infusion-related Reaction (IRR) 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 |
| during or after receiving the first full 600mg dose infusion on day 168. |
| Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 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. | After the infusions on day 0, day 14, and day 168. |
| Stanford Sleepiness Scale (SSS) Score on Days 0, 14, and 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. | after the infusions on day 0, day 14, and day 168. |
| Visual Analog Scale for Fatigue (VAS-F) Score on Days 0, 14 and 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. | after the infusions on day 0, day 14, and day 168. |
| Modified Fatigue Impact Scale (MFIS) Score on 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. | at day 168. |
| Multiple Sclerosis Impact Scale (MSIS-29) Score on Day168 | 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) | at day 168. |
| Result |
| Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234. doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21. |
| 28002688 | Result | Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS; ORATORIO Clinical Investigators. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21. |
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion.
antihistamine: prophylaxis
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Age at MS symptoms onset | Median | Inter-Quartile Range | years |
|
| Age at MS diagnosis | Median | Inter-Quartile Range | years |
|
| From MS symptoms onset to MS Diagnosis | Median | Inter-Quartile Range | weeks |
|
| Age at OCR start | Median | Inter-Quartile Range | years |
|
| Education | Count of Participants | Participants |
|
| Employment | Count of Participants | Participants |
|
| MS Type | Participants are categorized as having Primary Progressive Multiple Sclerosis (PPMS), Relapsing-Remitting Multiple Sclerosis (RMS), or Secondary Progressive Multiple Sclerosis (SPMS) based on the review of their disease and medical history. | Count of Participants | Participants |
|
| Reason start OCR | Count of Participants | Participants |
|
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion. antihistamine: prophylaxis |
|
|
| Secondary | Proportion of Participants With Infusion-related Reaction (IRR) 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 | Posted | Number | participants | during or after receiving the second half dose infusion on day 14. |
|
|
|
| Secondary | Proportion of Participants With an Infusion-related Reaction (IRR) 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 | Posted | Number | participants | during or after receiving the first full 600mg dose infusion on day 168. |
|
|
|
| Secondary | Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 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. | Posted | Mean | Standard Deviation | score on a scale | After the infusions on day 0, day 14, and day 168. |
|
|
|
| Secondary | Stanford Sleepiness Scale (SSS) Score on Days 0, 14, and 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. | Posted | Mean | Standard Deviation | score on a scale | after the infusions on day 0, day 14, and day 168. |
|
|
|
| Secondary | Visual Analog Scale for Fatigue (VAS-F) Score on Days 0, 14 and 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. | Posted | Mean | Standard Deviation | score on a scale | after the infusions on day 0, day 14, and day 168. |
|
|
|
| Secondary | Modified Fatigue Impact Scale (MFIS) Score on 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. | Posted | Mean | Standard Deviation | score on a scale | at day 168. |
|
|
|
| Secondary | Multiple Sclerosis Impact Scale (MSIS-29) Score on Day168 | 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) | Posted | Mean | Standard Deviation | score on a scale | at day 168. |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 7 |
| 9 |
| EG001 | Cetirizine | 10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be given orally 30-60 minutes prior to ocrelizumab infusion. antihistamine: prophylaxis | 0 | 10 | 0 | 10 | 8 | 10 |
|
| Infusion-related reaction | Immune system disorders | NCI CTCAE (v5.0) | Systematic Assessment | IRR after the first two infusions of dose 1 (each 300mg) |
|
| Infusion-related reaction | Immune system disorders | NCI CTCAE (v5.0) | Systematic Assessment | Overall IRRs occurred at the end of the study after infusion of dose 2 |
|
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| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| Side Effects- Day 0 |
|
| Convenience- Day 0 |
|
| Global Satisfaction- Day 14 |
|
| Effectiveness- Day 14 |
|
| Side Effects- Day 14 |
|
| Convenience- Day 14 |
|
| Global Satisfaction- Day 168 |
|
| Effectiveness- Day 168 |
|
| Side Effects- day 168 |
|
| Convenience- Day 168 |
|
| Day 168 |
|
| Fatigue- Day 14 |
|
| Energy- Day 14 |
|
| Fatigue- Day 168 |
|
| Energy- Day 168 |
|