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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rHuPH20 | Experimental | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rHuPH20 | Drug | 0.25 milliliter (mL) Intradermal (ID) syringe push bolus injection of rHuPH20 |
| |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ikeadi M Ndukwu, M.D., MPH | Saint Anthony Memorial Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Symbio Phase I Unit, Saint Anthony Memorial Research Center | Michigan City | Indiana | 46360 | United States |
This study involved 2 regimens which ran in parallel. Each participant's upper back was divided into 2 equal spaces for Regimen 1 and 2. Each of the 4 treatment sites in each space was independently randomized to placebo or rHuPH20 treatment in a 1:1 ratio. Thus, each participant served as their own control.
Participants with a known history of nickel allergy were recruited. At screening, the nickel sulfate concentration (1%, 2.5%, or 5%), applied to the skin of the upper back with a patch, that caused no more than a ++ reaction according to the scale of the International Contact Dermatitis Research Group (ICDRG) was determined. This concentration was used to elicit cutaneous reactions during the study period.
| ID | Title | Description |
|---|---|---|
| FG000 | Overall Study (rHuPH20 and Placebo) | Participant's upper back was divided into two equal spaces and received Regimen 1 and 2 in 4 spaces respectively. In Regimen 1, a single row of 4 patches, each with the nickel sulfate concentration (1, 2.5, or 5%) determined at screening, was applied to the upper space at Day 1. After 48 hours (Day 3), the patches were removed and the reactions were graded on the ICDRG scale. A 0.25 milliliters (mL) intradermal injection containing rHuPH20 (3,000 units [U]) or placebo (excipient) was administered once daily for 5 days at the center of each area of reaction. In Regimen 2, a single row of 4 sites in the lower space was injected intradermally with 0.25 mL of study material drug rHuPH20 (3,000 U) or placebo (excipient), in a randomly assigned 2:2 ratio at Day 1. Exactly ten minutes after the injections, patches with the nickel sulfate concentration (1, 2.5, or 5%) determined at screening were applied to the injection sites. After 48 hours (Day 3), the patches were removed and the reactions graded on the ICDRG scale. As during pretreatment, a 0.25 mL intradermal injection containing rHuPH20 or placebo was then administered once daily for 5 days at the center of each area of reaction. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The intent-to-treat (ITT) population included all enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study (rHuPH20 and Placebo) | Participant's upper back was divided into two equal spaces and received Regimen 1 and 2 in 4 spaces respectively. In Regimen 1, a single row of 4 patches, each with the nickel sulfate concentration (1, 2.5, or 5%) determined at screening, was applied to the upper space at Day 1. After 48 hours (Day 3), the patches were removed and the reactions were graded on the ICDRG scale. A 0.25 mL intradermal injection containing rHuPH20 (3,000 U) or placebo (excipient) was administered once daily for 5 days at the center of each area of reaction. In Regimen 2, a single row of 4 sites in the lower space was injected intradermally with 0.25 mL of study material drug rHuPH20 (3,000 U) or placebo (excipient), in a randomly assigned 2:2 ratio at Day 1. Exactly ten minutes after the injections, patches with the nickel sulfate concentration (1, 2.5, or 5%) determined at screening were applied to the injection sites. After 48 hours (Day 3), the patches were removed and the reactions graded on the ICDRG scale. As during pretreatment, a 0.25 mL intradermal injection containing rHuPH20 or placebo was then administered once daily for 5 days at the center of each area of reaction. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The Evaluable population included all evaluable participants who had completed dosing (or prematurely discontinued the administration due to a toxicity) and had undergone sufficient assessments to allow an assessment of the tolerability of the administration. | Posted | Count of Participants | Participants | Day 3 (48 hours post-dose after the patch removal for Regimen 1) up to Day 14 |
|
Baseline up to Day 14
The Safety population included all participants who received at least one dose of study drug. Adverse Events were only monitored/assessed on the whole participant level irrespective of different treatment regimen.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Overall Study (rHuPH20 and Placebo) | Participant's upper back was divided into two equal spaces and received Regimen 1 and 2 in 4 spaces respectively. In Regimen 1, a single row of 4 patches, each with the nickel sulfate concentration (1, 2.5, or 5%) determined at screening, was applied to the upper space at Day 1. After 48 hours (Day 3), the patches were removed and the reactions were graded on the ICDRG scale. A 0.25 mL intradermal injection containing rHuPH20 (3,000 U) or placebo (excipient) was administered once daily for 5 days at the center of each area of reaction. In Regimen 2, a single row of 4 sites in the lower space was injected intradermally with 0.25 mL of study material drug rHuPH20 (3,000 U) or placebo (excipient), in a randomly assigned 2:2 ratio at Day 1. Exactly ten minutes after the injections, patches with the nickel sulfate concentration (1, 2.5, or 5%) determined at screening were applied to the injection sites. After 48 hours (Day 3), the patches were removed and the reactions graded on the ICDRG scale. As during pretreatment, a 0.25 mL intradermal injection containing rHuPH20 or placebo was then administered once daily for 5 days at the center of each area of reaction. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site pain | General disorders | MedDRA v12.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Halozyme Therapeutics | 855-495-3639 | halozyme@EVERSANA.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 27, 2009 | Aug 23, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 9, 2009 | Aug 23, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D017449 | Dermatitis, Allergic Contact |
| ID | Term |
|---|---|
| D003877 | Dermatitis, Contact |
| D003872 | Dermatitis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| Placebo |
| Drug |
0.25 mL ID syringe push bolus injection of placebo control |
|
| 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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 | Overall Study (rHuPH20 and Placebo) | Participant's upper back was divided into two equal spaces and received Regimen 1 and 2 in 4 spaces respectively. In Regimen 1, a single row of 4 patches, each with the nickel sulfate concentration (1, 2.5, or 5%) determined at screening, was applied to the upper space at Day 1. After 48 hours (Day 3), the patches were removed and the reactions were graded on the ICDRG scale. A 0.25 mL intradermal injection containing rHuPH20 (3,000 U) or placebo (excipient) was administered once daily for 5 days at the center of each area of reaction. In Regimen 2, a single row of 4 sites in the lower space was injected intradermally with 0.25 mL of study material drug rHuPH20 (3,000 U) or placebo (excipient), in a randomly assigned 2:2 ratio at Day 1. Exactly ten minutes after the injections, patches with the nickel sulfate concentration (1, 2.5, or 5%) determined at screening were applied to the injection sites. After 48 hours (Day 3), the patches were removed and the reactions graded on the ICDRG scale. As during pretreatment, a 0.25 mL intradermal injection containing rHuPH20 or placebo was then administered once daily for 5 days at the center of each area of reaction. |
|
|
| Primary | 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. | The Evaluable population included all evaluable participants who had completed dosing (or prematurely discontinued the administration due to a toxicity) and had undergone sufficient assessments to allow an assessment of the tolerability of the administration. | Posted | Count of Participants | Participants | Day 3 (48 hours post-dose after the patch removal for Regimen 2) up to Day 14 |
|
|
|
| Secondary | 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. | The Evaluable population included all evaluable participants who had completed dosing (or prematurely discontinued the administration due to a toxicity) and had undergone sufficient assessments to allow an assessment of the tolerability of the administration. | Posted | Number | percentage of participants | Day 3 (48 hours post-dose after the patch removal for Regimen 1) |
|
|
|
| Secondary | 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. | The Evaluable population included all evaluable participants who had completed dosing (or prematurely discontinued the administration due to a toxicity) and had undergone sufficient assessments to allow an assessment of the tolerability of the administration. | Posted | Number | percentage of participants | Day 3 (48 hours post-dose after the patch removal for Regimen 2) |
|
|
|
| Secondary | 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. | The Safety population included all participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Baseline up to Day 14 |
|
|
|
| 0 |
| 21 |
| 21 |
| 21 |
| Injection site pruritus | General disorders | MedDRA v12.0 | Systematic Assessment |
|
| Injection site discomfort | General disorders | MedDRA v12.0 | Systematic Assessment |
|
| Injection site haematoma | General disorders | MedDRA v12.0 | Systematic Assessment |
|
| Injection site irritation | General disorders | MedDRA v12.0 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA v12.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA v12.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA v12.0 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA v12.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA v12.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA v12.0 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA v12.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA v12.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA v12.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v12.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v12.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v12.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v12.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v12.0 | Systematic Assessment |
|
| Sensation of heaviness | Musculoskeletal and connective tissue disorders | MedDRA v12.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v12.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA v12.0 | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA v12.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v12.0 | Systematic Assessment |
|
| Hyperventilation | Respiratory, thoracic and mediastinal disorders | MedDRA v12.0 | Systematic Assessment |
|
The PI must submit a copy of the proposed publication to the Sponsor 30 days prior to date of submission for publication. They can request a delay of up to 90 days if it is determined there is any patentable subject matter or confidential Information. Sponsor can make changes to the communication to remove sponsor's confidential information from it prior to publication.
| D017443 |
| Skin Diseases, Eczematous |
| D006968 | Hypersensitivity, Delayed |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |