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

NCT ID: NCT04175834

Last Updated: 2024-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-05
• Study Completion Date: 2022-05-13

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).

Conditions

Multiple Sclerosis; Infusion Reaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

diphenhydramine

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

Group Type: OTHER

diphenhydramine

Intervention Type: DRUG

prophylaxis

cetirizine

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

Group Type: ACTIVE_COMPARATOR

cetrizine

Intervention Type: DRUG

prophylaxis

Interventions

cetrizine

prophylaxis

Intervention Type: DRUG

diphenhydramine

prophylaxis

Intervention Type: DRUG

Other Intervention Names

Active comparator; Other

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Providence Health & Services

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kyle Smoot, MD

Role: PRINCIPAL_INVESTIGATOR

Providence Health & Services

Locations

Providence Neurological Specialties West

Portland, Oregon, United States

Countries

United States

References

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

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

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.

Reference Type: RESULT

PMID: 28002679 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28002688 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRECEPT

Identifier Type: OTHER

Identifier Source: secondary_id

ML41308

Identifier Type: -

Identifier Source: org_study_id