Comparing Risk and Severity of IRRs in Patients Premedicated With Cetirizine vs. Diphenhydramine Prior to Ocrelizumab

Multiple Sclerosis Clinical Trial

— PRECEPT  

Official title:

Comparing the Risk and Severity of Infusion-Related Reactions in Patients Premedicated With Cetirizine Versus Diphenhydramine Prior to Ocrelizumab Infusions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04175834
• Other study ID #: ML41308
• Secondary ID: PRECEPT
• Status: Completed
• Phase: Phase 3
• Start date: February 5, 2020
• Est. completion date: May 13, 2022

Study information

• Verified date: February 2024
• Source: Providence Health & Services
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: May 13, 2022
• Est. primary completion date: May 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infusion Reaction
• Multiple Sclerosis

Intervention

Drug:
• cetrizine
prophylaxis
• diphenhydramine
prophylaxis

Locations

Country	Name	City	State
United States	Providence Neurological Specialties West	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Providence Health & Services	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (7)

Genentech Inc. Ocrevus: Highlights of Prescribing Information. 2018; https://www.gene.com/download/pdf/ocrevus_prescribing.pdf. Accessed 02/13/2019.

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 O — View 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.

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 C — View 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.

National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. Accessed 02/13/19, 2019.

US Food and Drug Administration. Non-Inferiority Clinical Trials to Establish Effectiveness: Guidance for Industry. 2016.

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	During or after the first-half dose of the first infusion on day 0
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	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	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.	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.	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.	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.	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)	at day 168.