Study of the Intradermal Injection of rHuPH20 or Placebo in Participants With Nickel Allergic Contact Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to compare the effect and safety of rHuPH20 or placebo for the prevention and treatment of skin allergic reaction to nickel. The study drug and placebo will be administered by intradermal injection.

Detailed Description
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This study will involve 2 regimens which will run in parallel. Each participant's upper back will be divided into 2 equal spaces for Regimen 1 and 2. Each of the 4 treatment sites in each space will be independently randomized to placebo or rHuPH20 treatment in a 1:1 ratio. Thus, each participant will serve as their own control. Regimen 1 will evaluate the treatment of cutaneous reactions to nickel and Regimen 2 will evaluate the prevention as well as the treatment of cutaneous reactions to nickel. At screening, the nickel sulfate concentration (1%, 2.5%, or 5%) applied to the skin of the upper back with a patch, that will cause no more than a ++ reaction according to the scale of the International Contact Dermatitis Research Group (ICDRG) will be determined. This concentration will be used to elicit cutaneous reactions during the study period.

Official Title
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A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Study of the Intradermal Injection of rHuPH20 or Placebo in Subjects With Nickel Allergic Contact Dermatitis

Conditions
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Dermatitis, Allergic Contact

Intervention / Treatment
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* Drug: rHuPH20
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females 18-60 years of age. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study. Known contact dermatitis to nickel with a confirmed positive patch-test result to nickel sulfate. Intact normal skin without potentially obscuring tattoos, acne, dermatitis, pigmentation or lesions on the posterior aspect of the torso (back) in the area intended for allergen testing and dose administration. Vital signs (blood pressure [BP], heart rate [HR], temperature, respiratory rate) within normal range or, if out of range, assessed by the Investigator as not clinically significant and it is mutually agreed by both Investigator and sponsor medical monitor that the participant need not be excluded from the study for this reason. A negative serum or urine pregnancy test (if female of child-bearing potential) within 14 days of initial study drug administration. Participant should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug injections and assessments required in this protocol. Decision-making capacity and willingness and ability to comply with the requirements for full completion of the study. Signed, written Institutional Review Board (IRB)/Ethics Committee (EC)-approved informed consent. Exclusion Criteria: Nickel allergen patch test greater than a ++ reaction. Participants who were treated with chemotherapy agents or systemic corticosteroids within the past 3 months. Use of topical steroids, antihistamines, or immunosuppressants used near the site of allergen testing/injection within 14 days. Use of oral antihistamines within 14 days of study conduct. Extensive ongoing outbreaks of contact dermatitis anywhere on the body. Pregnant or women who are breast-feeding. Participants with a current disease state that can affect immune response (for example, flu, cancer, human immunodeficiency virus [HIV]). Known allergy to any hyaluronidase or the ingredients in the dose preparation. History of autoimmune disorder. Participants with any other medical condition that, in the opinion of the investigator, might significantly affect their ability to safely participate in the study or affect the conduct of this study. Examples might include asthma, diabetes, heart disease, epilepsy, cancer, etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rHuPH20<br>Participant's upper back will be divided into 2 equal spaces and will receive Regimen 1 and 2 in 4 spaces respectively. In Regimen 1, a single row of 4 patches, each with the nickel sulfate concentration (NSC) (1, 2.5, or 5%) determined at screening, will be applied to the upper space at Day 1. After 48 hours, the patches will be removed and the reactions will be graded on the ICDRG scale. An ID injection containing rHuPH20 (3,000 Units [U]) will be administered once daily (QD) for 5 days at the center of each area of reaction. In Regimen 2, a single row of 4 sites in the lower space will be injected intradermally with drug rHuPH20 (3,000 U) at Day 1. Ten minutes after the injections, patches with the NSC (1, 2.5, or 5%) determined at screening will be applied to the injection sites. After 48 hours, the patches will be removed and the reactions will be graded on the ICDRG scale. As during pretreatment, an ID injection containing rHuPH20 will be then administered QD for 5 days. | Drug: rHuPH20<br>* 0.25 milliliter (mL) Intradermal (ID) syringe push bolus injection of rHuPH20<br>|
| Placebo Comparator: Placebo<br>Participant's upper back will be divided into 2 equal spaces and will receive Regimen 1 and 2 in 4 spaces respectively. In Regimen 1, a single row of 4 patches, each with the NSC (1, 2.5, or 5%) determined at screening, will be applied to the upper space at Day 1. After 48 hours, the patches will be removed and the reactions will be graded on the ICDRG scale. An ID injection containing placebo will be administered QD for 5 days at the center of each area of reaction. In Regimen 2, a single row of 4 sites in the lower space will be injected intradermally with placebo at Day 1. Ten minutes after the injections, patches with the NSC (1, 2.5, or 5%) determined at screening will be applied to the injection sites. After 48 hours, the patches will be removed and the reactions will be graded on the ICDRG scale. As during pretreatment, an ID injection containing placebo will be then administered QD for 5 days. | Drug: Placebo<br>* 0.25 mL ID syringe push bolus injection of placebo control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive Reaction Scores Based Upon ICDRG Scoring Scale: Regimen 1 | Cutaneous reactions at the patch test sites were scored according to the ICDRG scoring scale as Grade 0 (-)= Negative reaction, Grade 1/2 (?)= Doubtful reaction; faint macular erythema only, Grade 1 (1+)= Weak (nonvesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 2 (2+): Strong (vesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 3 (3+): Extreme positive reaction; bullous reaction Grade NA (IR): Irritant reaction of different types. Participants with positive reaction scores (>= Grade 1) have been reported in this outcome measure. | Day 3 (48 hours post-dose after the patch removal for Regimen 1) up to Day 14 | 
| Number of Participants With Positive Reaction Scores Based Upon ICDRG Scoring Scale: Regimen 2 | Cutaneous reactions at the patch test sites were scored according to the ICDRG scoring scale as Grade 0 (-)= Negative reaction, Grade 1/2 (?)= Doubtful reaction; faint macular erythema only, Grade 1 (1+)= Weak (nonvesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 2 (2+): Strong (vesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 3 (3+): Extreme positive reaction; bullous reaction Grade NA (IR): Irritant reaction of different types. Participants with positive reaction scores (>= Grade 1) have been reported in this outcome measure. | Day 3 (48 hours post-dose after the patch removal for Regimen 2) up to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a >=1 Grade Change in ICDRG Score in at Least One Patch Region After Treatment With rHuPH20 or Placebo: Regimen 1 | Cutaneous reactions at the patch test sites were scored according to the ICDRG scoring scale as Grade 0 (-)= Negative reaction, Grade 1/2 (?)= Doubtful reaction; faint macular erythema only, Grade 1 (1+)= Weak (nonvesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 2 (2+): Strong (vesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 3 (3+): Extreme positive reaction; bullous reaction Grade NA (IR): Irritant reaction of different types. | Day 3 (48 hours post-dose after the patch removal for Regimen 1) | 
| Percentage of Participants With a >=1 Grade Change in ICDRG Score in at Least One Patch Region After Treatment With rHuPH20 or Placebo: Regimen 2 | Cutaneous reactions at the patch test sites were scored according to the ICDRG scoring scale as Grade 0 (-)= Negative reaction, Grade 1/2 (?)= Doubtful reaction; faint macular erythema only, Grade 1 (1+)= Weak (nonvesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 2 (2+): Strong (vesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 3 (3+): Extreme positive reaction; bullous reaction Grade NA (IR): Irritant reaction of different types. | Day 3 (48 hours post-dose after the patch removal for Regimen 2) | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs were defined as adverse events (AEs) with an onset during or following administration of the first dose of study drug. AEs were defined as any untoward medical occurrence in a participant administered study drug and that did not necessarily have a causal relationship with the study drug. SAEs were defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, an important medical event. Adverse Events were only monitored/assessed on the whole participant level irrespective of different treatment regimen. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section. | Baseline up to Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rHuPH20, Recombinant Human hyaluronidase