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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01689363

Acronym

H001-A2

Enrollment

253

Registered

2012-09-21

Start date

2012-09-30

Completion date

2012-12-31

Last updated

2017-01-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Allergic Skin Reaction

Keywords

hyaluronidase, enzymes with tissue spreading activity, allergic reaction, intradermal skin testing

Brief summary

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

Interventions

DRUGHyaluronidase

Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two random sites on their forearms.

DRUGHistamine

Subjects received one intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one random sites on their forearms.

DRUGSaline

Subjects received one intradermal injection of 0.02 mL saline at one random site on their forearm.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

SCREENING

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Positive Allergic Reaction to Amphadase® in the Per-Protocol Population (PPP)	Up to 30 minutes after the final study drug injection	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.
Positive Allergic Reaction to Amphadase® in the Intent-to-Treat Population (ITT)	Up to 30 minutes after the final study drug injection	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.

Secondary

Measure	Time frame	Description
Allergic Wheal Size in the Per-Protocol Population (PPP)	Up to 30 minutes after the final study drug injection	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.
Allergic Erythema Size in the Per-Protocol Population (PPP)	Up to 30 minutes after the final study drug injection	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.
Local Itchiness Rate in the Per-Protocol Population (PPP)	Up to 30 minutes after the final study drug injection	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.
Erythema Responder Rate in the Per-Protocol Population (PPP)	Up to 30 minutes after the final study drug injection	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.
Observed Wheal Size in the Intent-to-Treat Population (ITT)	Up to 30 minutes after the final study drug injection	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.
Observed Erythema Size in the Per-Protocol Population (PPP)	Up to 30 minutes after the final study drug injection	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.
Allergic Erythema Size in the Intent-to-Treat Population (ITT)	Up to 30 minutes after the final study drug injection	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.
Local Itchiness Rate in the Intent-to-Treat Population (ITT)	Up to 30 minutes after the final study drug injection	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.
Erythema Responder Rate in the Intent-to-Treat Population (ITT)	Up to 30 minutes after the final study drug injection	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.
Allergic Wheal Size in the Intent-to-Treat Population (ITT)	Up to 30 minutes after the final study drug injection	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.
Observed Erythema Size in the Intent-to-Treat Population (ITT)	Up to 30 minutes after the final study drug injection	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.
Observed Wheal Size in the Per-Protocol Population (PPP)	Up to 30 minutes after the final study drug injection	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Total Study Population Subjects received four intradermal injections of study drug (two injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL), one injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL), one injection of 0.02 mL saline) in a random order at four locations on the subjects' forearms.	253
Total	253

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007
Overall Study	Protocol Violation	0	1	0	0	0	0	0	0

Baseline characteristics

Characteristic	Total Study Population
Age, Categorical <=18 years	7 Participants
Age, Categorical >=65 years	7 Participants
Age, Categorical Between 18 and 65 years	239 Participants
Age, Continuous	34.9 years STANDARD_DEVIATION 14
Region of Enrollment United States	253 participants
Sex: Female, Male Female	127 Participants
Sex: Female, Male Male	126 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	0 / 253	0 / 253	0 / 253	0 / 253
serious Total, serious adverse events	0 / 253	0 / 253	0 / 253	0 / 253

Outcome results

Primary

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.