Phase 2 Study IV QUZYTTIR™ (Cetirizine Hydrochloride Injection) vs V Diphenhydramine

This will be a randomized, double-blind exploratory study of IV cetirizine HCl 10 mg/mL versus IV diphenhydramine 50 mg/mL in approximately 34 patients who require premedication for hypersensitivity infusion reactions associated with an anti-CD20 such as Rituxan® (rituximab) or Paclitaxel. The objectives and purpose of the study will be described to patients presenting at the participating infusion centers. The patients will be randomized to receive either IV cetirizine HCl or IV diphenhydramine.

• Cetirizine HCl 10 mg/mL (Drug), also known as Quzyttir™: Comparison of two injectable products: cetirizine HCl 10 mg/mL and diphenhydramine 50 mg/mL, both administered during a 1 to 2-minute period by IV push using a 1 mL syringe
• Diphenhydramine 50 mg/mL (Drug), also known as Benadryl injection®: Comparison of two injectable products: cetirizine HCl 10 mg/mL and diphenhydramine 50 mg/mL, both administered during a 1 to 2-minute period by IV push using a 1 mL syringe
• anti-CD20 such as Rituximab or Paclitaxel (Drug), also known as Rituxan®, Taxol, Arzerra, Ocrevus, Gazyva, Ruxience, Truxima, Zevalin: Compare the number of infusion reactions to treatment with an anti-CD20 such as Rituxan® (Rituximab) or Taxol® (Paclitaxel) after premedication with intravenous (IV) QUZYTTIR™ cetirizine hydrochloride (HCl) or IV diphenhydramine during first-cycle infusion or re-treatment. Re-treatment is defined as re-treatment with Rituxan® (Rituximab) or Paclitaxel after 6 months in patients with persistent infusion reactions while on maintenance or re-treatment.

Primary outcomes

• Number of Hypersensitivity Reactions to Treatment With an Anti-CD20 Antibody or Paclitaxel [During and after anti-CD20 agent or paclitaxel infusion, at 1 and 2 hours after the antihistamine injection, at time of discharge, and up through 1 Month post injection of antihistamine (intervention).]: Compare the number of patients experiencing any infusion reaction events, and the number and percentage of patients experiencing each symptom of infusion reactions (flushing, itching, alterations in heart rate and blood pressure, dyspnea, chest discomfort, acute back or abdominal pain, fever, shaking chills, nausea, vomiting, diarrhea, skin rashes, throat tightening, hypoxia, seizures, dizziness, or syncope) to treatment with anti-CD20 such as Rituxan® (rituximab) or Paclitaxel after premedication with intravenous (IV) QUZYTTIR™ cetirizine hydrochloride (HCl) or IV diphenhydramine during first-cycle infusion or re-treatment after 6 months or in patients with persistent infusion reactions while on maintenance with anti-CD20 such as Rituxan® (rituximab) or Paclitaxel. The infusion reactions will be evaluated following the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) definitions of graded infusion reactions.

Secondary outcomes

• Patient Sedation Scores at 1 Hour and 2 Hours Post-injection of Antihistamine (IV Cetirizine HCl or IV Diphenhydramine) and at Discharge. [1 hour, 2 Hours and at discharge]: Patient sedation scores at 1 hour and 2 hours post-injection of antihistamine (IV cetirizine HCl or IV diphenhydramine) and at discharge. The patient sedation scores are assessed on a scale of 0-4, with 0=None and 4=Extremely Severe (Asleep, Cannot Self-Rate). The HCP sedation scores are assessed on a scale of 0-4, with 0=None and 4=Extremely severe.
• Time From Injection to "Readiness for Discharge" [Time to discharge from infusion center]: Describe the distribution of the amount of time spent in the treatment center prior to discharge (time from injection to "Readiness for Discharge").

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Male or female patients who require treatment premedication with an antihistamine for hypersensitivity infusion reactions associated with an anti-CD20, such as Rituxan® (Rituximab) or Paclitaxel, in their first-cycle or re-treatment after 6 months or in patients with persistent infusion reactions while on maintenance or re-treatment.
* 18 years of age or older

Exclusion Criteria:

* Receipt of an investigational drug or device within the past 30 days.
* Patients with likelihood of developing or history of tumor lysis syndrome.(TLS): patients with auto-lyse, Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL) with bulky disease (single node 7 or more cm or 3 or more nodal sites with size 3 or more cm)
* Patients in whom an antihistamine may be contraindicated (e.g., narrow angle glaucoma, symptomatic prostatic hypertrophy).
* Patients who, in the opinion of the investigator, may not tolerate an IV injection of diphenhydramine 50 mg or cetirizine HCl 10 mg.
* Receipt of any antihistamine (H1 antagonist) within the past 2 hours regardless of the route of administration, e.g., diphenhydramine, cetirizine, loratadine, fexofenadine, levocetirizine, desloratadine. chlorpheniramine, clemastine, and doxylamine
* Receipt of an H2 antagonist within the past 4 hours, e.g., ranitidine, cimetidine, famotidine, nizatidine.
* Receipt of doxepin within the past 24 hours; doxepin is an antidepressant, but it also has antihistamine properties.
* Receipt of epinephrine (EpiPen® or any other brand) within the past 30 days.
* Has known allergy to hydroxyzine, cetirizine, or levocetirizine, or diphenhydramine.
* Pregnant or breastfeeding.
* Any condition that in the view of the investigator makes the patient unsuitable for enrollment in this study.
* Major medical or psychiatric illness, other than diagnosed cancer at the time of presentation or in the past that in the investigator's judgement they should not be enrolled in this clinical trial.
* Inability to provide informed consent.
* Patients on concomitant P-glycoprotein inhibitors; including antidepressants, antipsychotics (e.g., olanzapine), and benzodiazepines (e.g., alprazolam), as they may cause an increase in sedation.
* Receipt of drugs that cause sedation within the past 24 hours prior to administration of the study drug.

Participant flow

Outcome results

• Number of Hypersensitivity Reactions to Treatment With an Anti-CD20 Antibody or Paclitaxel (Primary), Count of participants, Participants: Cohort A 2; Cohort B 3
• Patient Sedation Scores at 1 Hour and 2 Hours Post-injection of Antihistamine (IV Cetirizine HCl or IV Diphenhydramine) and at Discharge. (Secondary), Mean, Units on a scale: Cohort A 0.5 +/- 0.72; Cohort B 1.3 +/- 1.26
• Time From Injection to "Readiness for Discharge" (Secondary), Mean, Hours: Cohort A 4.3 +/- 1.54; Cohort B 4.7 +/- 1.26

Adverse events

Time frame: 1 month

Serious adverse events by term

• Results publication: Holmes JP, Peguero JA, Garland RC, North J, Young S, Brent LD, Joseph-Ridge N. Intravenous Cetirizine vs Intravenous Diphenhydramine for the Prevention of Hypersensitivity Infusion Reactions: Results of an Exploratory Phase 2 Study. J Infus Nurs. 2021 Nov-Dec 01;44(6):315-322. doi: 10.1097/NAN.0000000000000444. PMID 34555839

• Study Protocol (PDF, 2020-11-24)
• Statistical Analysis Plan (PDF, 2020-11-25)

• Janine North, B.S., Study director, TerSera Therapeutics