Evaluation of the Allergenicity of AMPHADASE INJECTION (Hyaluronidase Injection USP)

Study Overview
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Brief Summary
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This study is designed to evaluate the allergenicity of Amphadase® in healthy volunteers using an intradermal skin test.

Official Title
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A Randomized, Double-Blinded, Negative- and Positive-Controlled Study for Evaluation of the Allergenicity of Amphadase® in Healthy Volunteers Using Intradermal Skin Test

Conditions
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Allergic Skin Reaction

Intervention / Treatment
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* Drug: Hyaluronidase
* Drug: Histamine
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers of either gender; Those without clinically significant cardiovascular gastrointestinal, hepatic, neurological, psychiatric, endocrine, or other major systemic disease that would unduly risk the subject's safety or interfere with the interpretation of results, assessed according to the judgment of the Principal Investigator. A non-inclusive list which would not be exclusionary and define healthy individual for the purposes of this study are: hypothyroidism, stable hypertension except those subjects on beta blockers including ocular preparations, seasonal/perennial allergic rhinitis if able to wash out of antihistamines, stable, mild intermittent asthma (subjects using beta agonists as a monotherapy on an as-needed basis, excluding daily usage), migraine if not taking excluded medications, mild anxiety/depression if not taking excluded medications, and mild arthritic conditions if not taking excluded medications. Willingness and ability to sign an informed consent document; 18 - 80 years of age; Intact skin at the forearm ; Female participants are currently practicing effective birth control methods or abstinence. Exclusion Criteria: Known allergy, hypersensitivity or contraindications to hyaluronidase, thimerosal, edetate disodium (EDTA); Use of medications within a duration considered to interfere with skin testing. Known dermographism which may interfere with skin testing. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm H<br>Intradermal injection of Amphadase (hyaluronidase 150 USP units/mL) | Drug: Hyaluronidase<br>* Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two random sites on their forearms.<br>* Other names: Amphadase®;|
| Active Comparator: Arm P<br>Intradermal injection of Histatrol (histamine base 0.1 mg/mL) | Drug: Histamine<br>* Subjects received one intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one random sites on their forearms.<br>* Other names: Histatrol®;|
| Placebo Comparator: Arm N<br>Intradermal injection of saline (0.02 mL) | Drug: Saline<br>* Subjects received one intradermal injection of 0.02 mL saline at one random site on their forearm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive Allergic Reaction to Amphadase® in the Per-Protocol Population (PPP) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (>8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching. | Up to 30 minutes after the final study drug injection | 
| Positive Allergic Reaction to Amphadase® in the Intent-to-Treat Population (ITT) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (>8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching. | Up to 30 minutes after the final study drug injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed Wheal Size in the Per-Protocol Population (PPP) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Observed Erythema Size in the Per-Protocol Population (PPP) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Allergic Wheal Size in the Per-Protocol Population (PPP) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Allergic Erythema Size in the Per-Protocol Population (PPP) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Local Itchiness Rate in the Per-Protocol Population (PPP) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Erythema Responder Rate in the Per-Protocol Population (PPP) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Observed Wheal Size in the Intent-to-Treat Population (ITT) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Observed Erythema Size in the Intent-to-Treat Population (ITT) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Allergic Erythema Size in the Intent-to-Treat Population (ITT) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Local Itchiness Rate in the Intent-to-Treat Population (ITT) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Erythema Responder Rate in the Intent-to-Treat Population (ITT) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 
| Allergic Wheal Size in the Intent-to-Treat Population (ITT) | Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection. | Up to 30 minutes after the final study drug injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyaluronidase, enzymes with tissue spreading activity, allergic reaction, intradermal skin testing