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

Sponsor

Providence Health & Services (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04175834

Collaborator

Genentech, Inc. (Industry)

Enrollment

Location

Arms

51.8

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis Infusion Reaction	Drug: antihistamine	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 5, 2020

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

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: antihistamine prophylaxis Other Names: cetirizine
Active Comparator: cetirizine 10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion.	Drug: antihistamine prophylaxis Other Names: cetirizine

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: antihistamine

prophylaxis

Other Names:

cetirizine

Active Comparator: cetirizine

10 mg cetirizine tablet, generic, sourced from Mylan Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion.

Drug: antihistamine

prophylaxis

Other Names:

cetirizine

Outcome Measures

Primary Outcome Measures

Proportion of patients having infusion-related reaction [During or after the first-half dose of the first infusion on day 0]
defined by Common Terminology Criteria (CTCAE), version 4

Secondary Outcome Measures

Proportion of patients have an infusion-related reaction [during or after receiving the second half dose infusion on day 14.]
defined by Common Terminology Criteria (CTCAE), version 4
Proportion of patients have an infusion-related reaction [during or after receiving the first full 600mg dose infusion on week 24.]
defined by Common Terminology Criteria (CTCAE), version 4
Treatment Satisfaction Questionnaire for Medication score [After the infusions on day 0, day 14, and week 24. Higher the score, better the satisfaction]
Patient reported outcome
Stanford Sleepiness Scale score [after the infusions on day 0, day 14, and week 24. The higher the score, the sleepier the subject.]
Patient reported outcome
Visual Analog Scale for Fatigue score [after the infusions on day 0, day 14, and week 24. The higher the score, the the greater the subject's fatigue is.]
Patient reported outcome
Modified Fatigue Impact Scale score [at week 24. subject answers 21 questions related to fatigue in the past 4 weeks with choices of frequency: Never, Rarely, Sometimes, Often, or Almost always]
Patient reported outcome
Physical and psychological Multiple Sclerosis Impact Scale scores [at week 24 questionnaire asking subjects to rate their symptoms related to MS as 1-Not at all, 2-a little 3-Moderately or 4-Extremely-]
Patient reported outcome

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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