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

February 28, 2024 updated by: Providence Health & Services

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97225
        • Providence Neurological Specialties West

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: diphenhydramine
25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion.
Drug: diphenhydramine
prophylaxis
Other Names:
  • Other
Active Comparator: cetirizine
10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion.
Drug: cetrizine
prophylaxis
Other Names:
  • Active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants With Infusion-related Reaction (IRR) on Day 0
Time Frame: During or after the first-half dose of the first infusion 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants With Infusion-related Reaction (IRR) on Day 14
Time Frame: 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
during or after receiving the second half dose infusion on day 14.
Proportion of Participants With an Infusion-related Reaction (IRR) on Day 168
Time Frame: 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
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
Time Frame: 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.
After the infusions on day 0, day 14, and day 168.
Stanford Sleepiness Scale (SSS) Score on Days 0, 14, and 168
Time Frame: 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.
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
Time Frame: 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.
after the infusions on day 0, day 14, and day 168.
Modified Fatigue Impact Scale (MFIS) Score on Day 168
Time Frame: 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.
at day 168.
Multiple Sclerosis Impact Scale (MSIS-29) Score on Day168
Time Frame: 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)
at day 168.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Providence Health & Services

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Kyle Smoot, MD, Providence Health & Services

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 5, 2020

Primary Completion (Actual)

May 13, 2022

Study Completion (Actual)

May 13, 2022

Study Registration Dates

First Submitted

November 22, 2019

First Submitted That Met QC Criteria

November 22, 2019

First Posted (Actual)

November 25, 2019

Study Record Updates

Last Update Posted (Actual)

March 4, 2024

Last Update Submitted That Met QC Criteria

February 28, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML41308
  • PRECEPT (Other Identifier: Providence health & Services)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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