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

NCT04175834 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ML41308PRECEPT
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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).

Conditions

Multiple Sclerosis; Infusion Reaction

Keywords

cetirizine; diphenhydramine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Proportion of Participants With Infusion-related Reaction (IRR) 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

  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

  After the infusions on day 0, day 14, and day 168.

• Stanford Sleepiness Scale (SSS) Score on Days 0, 14, and 168

  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

  after the infusions on day 0, day 14, and day 168.

Study Arms (2)

diphenhydramine

OTHER

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

Drug: diphenhydramine

cetirizine

ACTIVE COMPARATOR

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

Drug: cetrizine

Interventions

cetrizine DRUG

prophylaxis

Also known as: Active comparator

cetirizine

diphenhydramine DRUG

prophylaxis

Also known as: Other

diphenhydramine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient with relapsing or progressive forms of Multiple Sclerosis (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 ocrelizumab (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.

You may not qualify if:

• 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 Human Immunodeficiency Virus (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.

Sponsors & Collaborators

• Providence Health & Services: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Providence Neurological Specialties West

Portland, Oregon, 97225, United States

Location

Related Publications (7)

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

  BACKGROUND

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

  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.

  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.

  BACKGROUND

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

  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.

  PMID: 28002679 RESULT

• 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.

  PMID: 28002688 RESULT

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Diphenhydramine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Chiayi Chen, Director of WC/PBSI Clinical Research Program
• Organization: Providence Health & Services

Chiayi.Chen@providence.org

503-216-1012

Study Officials

• Kyle Smoot, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 22, 2019
• First Posted: November 25, 2019
• Study Start: February 5, 2020
• Primary Completion: May 13, 2022
• Study Completion: May 13, 2022
• Last Updated: March 4, 2024
• Results First Posted: March 4, 2024

Record last verified: 2024-02

Locations

US (1)