Trial Outcomes & Findings for Study of the Intradermal Injection of rHuPH20 or Placebo in Participants With Nickel Allergic Contact Dermatitis (NCT NCT00928447)

Last Updated: 2021-12-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Day 3 (48 hours post-dose after the patch removal for Regimen 1) up to Day 14

Results posted on

2021-12-17

Participant Flow

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.

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.

Unit of analysis: Patch

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	22 176
Overall Study Received at Least 1 Dose of rHuPH20	21 168
Overall Study Received at Least 1 Dose of Placebo	21 168
Overall Study COMPLETED	20 160
Overall Study NOT COMPLETED	2 16

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Withdrawal by Subject	1
Overall Study Investigator's decision	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study (rHuPH20 and Placebo) n=22 Participants 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.
Age, Continuous	39.5 years STANDARD_DEVIATION 15.34 • n=93 Participants
Sex: Female, Male Female	22 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: Day 3 (48 hours post-dose after the patch removal for Regimen 1) up to Day 14

Population: 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.

Outcome measures

Outcome measures
Measure	Overall Study (rHuPH20 and Placebo) n=20 Participants 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.
Number of Participants With Positive Reaction Scores Based Upon ICDRG Scoring Scale: Regimen 1 rHuPH20	5 Participants
Number of Participants With Positive Reaction Scores Based Upon ICDRG Scoring Scale: Regimen 1 Placebo	9 Participants

PRIMARY outcome

Timeframe: Day 3 (48 hours post-dose after the patch removal for Regimen 2) up to Day 14

Outcome measures

Outcome measures
Measure	Overall Study (rHuPH20 and Placebo) n=20 Participants 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.
Number of Participants With Positive Reaction Scores Based Upon ICDRG Scoring Scale: Regimen 2 rHuPH20	3 Participants
Number of Participants With Positive Reaction Scores Based Upon ICDRG Scoring Scale: Regimen 2 Placebo	2 Participants

SECONDARY outcome

Timeframe: Day 3 (48 hours post-dose after the patch removal for Regimen 1)

Outcome measures

Outcome measures
Measure	Overall Study (rHuPH20 and Placebo) n=20 Participants 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.
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 rHuPH20	70 percentage of participants
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 Placebo	75 percentage of participants

SECONDARY outcome

Timeframe: Day 3 (48 hours post-dose after the patch removal for Regimen 2)

Outcome measures

Outcome measures
Measure	Overall Study (rHuPH20 and Placebo) n=20 Participants 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.
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 rHuPH20	95 percentage of participants
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 Placebo	90 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 14

Population: The Safety population included all participants who received at least one dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Overall Study (rHuPH20 and Placebo) n=21 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	21 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	0 Participants

Adverse Events

Overall Study (rHuPH20 and Placebo)

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Overall Study (rHuPH20 and Placebo) n=21 participants at risk 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.
General disorders Injection site pain	100.0% 21/21 • 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.
General disorders Injection site pruritus	85.7% 18/21 • 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.
General disorders Injection site discomfort	14.3% 3/21 • 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.
General disorders Injection site haematoma	14.3% 3/21 • 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.
General disorders Injection site irritation	14.3% 3/21 • 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.
General disorders Feeling hot	4.8% 1/21 • 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.
Nervous system disorders Headache	47.6% 10/21 • 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.
Nervous system disorders Dizziness	19.0% 4/21 • 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.
Nervous system disorders Syncope	4.8% 1/21 • 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.
Gastrointestinal disorders Nausea	9.5% 2/21 • 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.
Gastrointestinal disorders Vomiting	9.5% 2/21 • 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.
Gastrointestinal disorders Abdominal pain lower	4.8% 1/21 • 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.
Gastrointestinal disorders Diarrhoea	4.8% 1/21 • 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.
Gastrointestinal disorders Dry mouth	4.8% 1/21 • 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.
Gastrointestinal disorders Gastrooesophageal reflux disease	4.8% 1/21 • 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.
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 2/21 • 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.
Musculoskeletal and connective tissue disorders Back pain	4.8% 1/21 • 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.
Musculoskeletal and connective tissue disorders Myalgia	4.8% 1/21 • 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.
Musculoskeletal and connective tissue disorders Pain in extremity	4.8% 1/21 • 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.
Musculoskeletal and connective tissue disorders Sensation of heaviness	4.8% 1/21 • 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.
Skin and subcutaneous tissue disorders Pruritus	19.0% 4/21 • 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.
Skin and subcutaneous tissue disorders Rash	4.8% 1/21 • 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.
Immune system disorders Seasonal allergy	4.8% 1/21 • 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.8% 1/21 • 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.
Respiratory, thoracic and mediastinal disorders Hyperventilation	4.8% 1/21 • 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.

Additional Information

Chief Medical Officer

Halozyme Therapeutics

Phone: 855-495-3639

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
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