Clinical trial NCT04175834: Comparing Risk and Severity of IRRs in Patients Premedicated With Cetirizine vs. Diphenhydramine Prior to Ocrelizumab
Official title: Comparing the Risk and Severity of Infusion-Related Reactions in Patients Premedicated With Cetirizine Versus Diphenhydramine Prior to Ocrelizumab Infusions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Infusion Reaction
Keywords: cetirizine
diphenhydramine
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2019-11-25
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. Male or female patient with relapsing or progressive forms of Multiple Sclerosis (MS), age 18 to 70 inclusive at the time of consent.
2. Able to understand the purpose, responsibilities and risks of the study and provide signed informed consent.
3. Naïve to ocrelizumab (OCR) and will receive OCR as part of standard of care for MS treatment.
4. No evidence, in the opinion of the investigators of significant cognitive limitation or psychiatric disorder that would interfere with the conduct of the study.
5. Estimated Expanded Disability Status Scale (EDSS) of ≤ 6.5 at screening.
6. Female patients of childbearing potential must practice effective contraception and continue contraception during the study.

Exclusion Criteria:

1. Any mental condition of such that patient is unable to understand the nature, scope, and possible consequences of the study.
2. Evidence of active hepatitis B infection at screening.
3. Patients with untreated hepatitis C, or tuberculosis. Patients who have history of Progressive multifocal leukoencephalopathy (PML) or known to be Human Immunodeficiency Virus (HIV) positive, per standard care.
4. Any persistent or severe infection.
5. Pregnancy or lactation.
6. Significant, uncontrolled somatic disease or severe depression in the last year.
7. Current use of immunosuppressive medication, lymphocyte-depleting agents, or lymphocyte-trafficking blockers.
8. Patients with any significant comorbidity that in the opinion of the investigator, would interfere with participation in the study.
9. Any known allergy or inability to tolerate diphenhydramine or cetirizine.

Primary outcomes:
measure: Proportion of Participants With Infusion-related Reaction (IRR) on Day 0
timeFrame: During or after the first-half dose of the first infusion on day 0
Secondary outcomes:
measure: Proportion of Participants With Infusion-related Reaction (IRR) on Day 14
timeFrame: during or after receiving the second half dose infusion on day 14.
measure: Proportion of Participants With an Infusion-related Reaction (IRR) on Day 168
timeFrame: during or after receiving the first full 600mg dose infusion on day 168.
measure: Treatment Satisfaction Questionnaire for Medication (TSQM) Score on Days 0, 14 and 168
timeFrame: After the infusions on day 0, day 14, and day 168.
measure: Stanford Sleepiness Scale (SSS) Score on Days 0, 14, and 168
timeFrame: after the infusions on day 0, day 14, and day 168.
measure: Visual Analog Scale for Fatigue (VAS-F) Score on Days 0, 14 and 168
timeFrame: after the infusions on day 0, day 14, and day 168.
measure: Modified Fatigue Impact Scale (MFIS) Score on Day 168
timeFrame: at day 168.
measure: Multiple Sclerosis Impact Scale (MSIS-29) Score on Day168
timeFrame: at day 168.
Other outcomes:
Locations:
city: Portland
country: United States
facility: Providence Neurological Specialties West
state: Oregon
Study officials:
affiliation: Providence Health & Services
name: Kyle Smoot, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. Accessed 02/13/19, 2019.
citation: Genentech Inc. Ocrevus: Highlights of Prescribing Information. 2018; https://www.gene.com/download/pdf/ocrevus_prescribing.pdf. Accessed 02/13/2019.
citation: 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.
citation: 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.
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citation: 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.
citation: 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.