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

Primary Purpose

Multiple Sclerosis, Infusion Reaction

Status

Active

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

antihistamine

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring cetirizine, diphenhydramine

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Providence Neurological Specialties West

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Active Comparator

Arm Label

diphenhydramine

cetirizine

Arm Description

25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion.

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

Outcomes

Primary Outcome Measures

Proportion of patients having infusion-related reaction

defined by Common Terminology Criteria (CTCAE), version 4

Secondary Outcome Measures

Proportion of patients have an infusion-related reaction

defined by Common Terminology Criteria (CTCAE), version 4

Proportion of patients have an infusion-related reaction

defined by Common Terminology Criteria (CTCAE), version 4

Treatment Satisfaction Questionnaire for Medication score

Patient reported outcome

Stanford Sleepiness Scale score

Patient reported outcome

Visual Analog Scale for Fatigue score

Patient reported outcome

Modified Fatigue Impact Scale score

Patient reported outcome

Physical and psychological Multiple Sclerosis Impact Scale scores

Patient reported outcome

Full Information

NCT ID

NCT04175834

First Posted

November 22, 2019

Last Updated

January 10, 2022

Sponsor

Providence Health & Services

Collaborators

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04175834

Brief Title

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

Acronym

PRECEPT

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

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 5, 2020 (Actual)

Primary Completion Date

January 2023 (Anticipated)

Study Completion Date

June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Providence Health & Services

Collaborators

Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis, Infusion Reaction

Keywords

cetirizine, diphenhydramine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

diphenhydramine

Arm Type

Other

Arm Description

25 mg diphenhydramine capsule, generic, sourced from Major Pharmaceuticals will be give orally 30-60 minutes prior to ocrelizumab infusion.

Arm Title

cetirizine

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

antihistamine

Other Intervention Name(s)

cetirizine

Intervention Description

prophylaxis

Primary Outcome Measure Information:

Title

Proportion of patients having infusion-related reaction

Description

defined by Common Terminology Criteria (CTCAE), version 4

Time Frame

During or after the first-half dose of the first infusion on day 0

Secondary Outcome Measure Information:

Title

Proportion of patients have an infusion-related reaction

Description

defined by Common Terminology Criteria (CTCAE), version 4

Time Frame

during or after receiving the second half dose infusion on day 14.

Title

Proportion of patients have an infusion-related reaction

Description

defined by Common Terminology Criteria (CTCAE), version 4

Time Frame

during or after receiving the first full 600mg dose infusion on week 24.

Title

Treatment Satisfaction Questionnaire for Medication score

Description

Patient reported outcome

Time Frame

After the infusions on day 0, day 14, and week 24. Higher the score, better the satisfaction

Title

Stanford Sleepiness Scale score

Description

Patient reported outcome

Time Frame

after the infusions on day 0, day 14, and week 24. The higher the score, the sleepier the subject.

Title

Visual Analog Scale for Fatigue score

Description

Patient reported outcome

Time Frame

after the infusions on day 0, day 14, and week 24. The higher the score, the the greater the subject's fatigue is.

Title

Modified Fatigue Impact Scale score

Description

Patient reported outcome

Time Frame

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

Title

Physical and psychological Multiple Sclerosis Impact Scale scores

Description

Patient reported outcome

Time Frame

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-

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kyle Smoot, MD

Organizational Affiliation

Providence Health & Services

Official's Role

Principal Investigator

Facility Information:

Facility Name

Providence Neurological Specialties West

City

Portland

State/Province

Oregon

ZIP/Postal Code

97225

Country

United States

12. IPD Sharing Statement

Citations:

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.

Results Reference

background

Citation

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

Results Reference

background

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.

Results Reference

background

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.

Results Reference

background

Citation

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

Results Reference

background

PubMed Identifier

28002679

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.

Results Reference

result

PubMed Identifier

28002688

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.

Results Reference

result

Learn more about this trial

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

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