Clinical Evaluation of Metal Panel Allergens: Dose Response Study

Clinical Evaluation of Metal Panel Allergens: Aluminum, Copper, Manganese, Molybdenum, Tin, Titanium, Vanadium and Zinc Dose Response Study

48-hour application of metal allergen patches to test for potential allergic responses.

Study Overview

• Status: Completed
• Conditions: Dermatitis, Eczematous
• Intervention / Treatment: Biological: Metal Allergen Epicutaneous Patch

Detailed Description

A 48-hour application (approximate) of investigational allergen panels, excipient controls and corresponding reference allergens will be applied to the skin of human subjects to test for potential positive allergic responses. Test sites will be evaluated at 3-4, 7-8, 10-14 and 19-23 days after application. Ascending allergen dosages will be randomized within each panel into three different configurations which will be randomly assigned to subjects as they enter the study. The investigators and subjects will be aware of the allergens and the patch test doses but will not be aware of the location of individual allergens within each panel.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 80337
    • Ludwig-Maximilians-Universität München
• Italy
  • Milan, Italy, 20161
    • University of Milano
• Japan
  • Aichi, Japan, 470-1192
    • Fujita Health University School of medicine
  • Kyoto, Japan, 602-8566
    • Kyoto Prefectural University of Medicine
  • Tokushima, Japan, 770-8504
    • Tokushima University Graduate School
• Netherlands
  • Amsterdam, Netherlands, NL1081
    • VU University Medical Center
• Switzerland
  • Basel, Switzerland, CH-4031
    • University Hospital Basel Allergology Unit
• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health, University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years of age or older.
2. Past positive patch test result within the past 10 years (to one of the dilution series metals being tested on this study) or strong suspicion of metal contact allergy based on results of the Qualification Questionnaire.
3. Unable to become pregnant or willing to use an acceptable method of contraception to prevent pregnancy if female of childbearing potential; (Inability to become pregnant includes all male subjects and female subjects who are postmenopausal for at least 1 year, or surgically sterile- have had a hysterectomy, bilateral ovariectomy, uterine ablation or bilateral tubal ligation. Acceptable methods of contraception include: 1) systemic birth control; 2) double barrier method; 3) intrauterine device; 4) vasectomized partner; or 5) abstinence from sexual intercourse. Subject must agree to use acceptable contraception for the duration of the entire study.)
4. Understands and signs the approved Informed Consent form which is consistent with all institutional, local and national regulations.

Exclusion Criteria:

1. Breastfeeding or pregnant (as determined by urine pregnancy test) or intending to become pregnant during the course of the study.
2. Topical treatment with corticosteroids or other immunosuppressive agents on or near the test area during the 14 days prior to inclusion in this study.
3. Systemic treatment with corticosteroids (equivalent to > 10 mg prednisone) or other immunosuppressive agents during the 14 days prior to inclusion in this study. Inhaled treatments are permitted. NOTE: Steroidal nose or eye drops are permitted.
4. Treatment with ultraviolet (UV) light (including tanning) during the 3 weeks prior to inclusion in this study.
5. Acute dermatitis outbreak or dermatitis on or near the test area on the back.
6. Conditions such as; fibromyalgia, chronic fatigue, depression, cognitive impairment, flu-like symptoms, diarrhea and/or headache without at least one of the symptoms related to metal exposure listed in Section 10.1 under physical examination
7. Inability to comply with patch test study requirements including multiple return visits and activity restrictions (e.g., protecting test panels from excess moisture due to showering or vigorous activity).
8. Participation in a clinical trial of an investigational drug, treatment or device during this study or 3 weeks prior to inclusion in this study.
9. An opinion of the Investigator that deems the potential subject to be non-compliant, unable to return for study visits or complete the study as detailed in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metal Allergen Epicutaneous Patch; 8 allergens were tested. Not all subjects tested each allergen. Section reports number of subjects with positive responses to each allergen.	Biological: Metal Allergen Epicutaneous Patch; 48 hour application of metal allergen patch to diagnose contact dermatitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Patch Test Responses	Allergen patch test sites were scored at Visit 3 (day 3-4) Visit 4 (day 7-8) Visit 5 (day 10-14) and Visit 6 Day 19-23). Determination of positive or negative test response for each allergen dose was assessed by the investigator following the final visit.	21 days post patch application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Panel Adhesion	Panel Adhesion was measured at Visit 2 (day 2) prior to panel removal according to the following scale: Excellent- Skin contact good; all tape edges adherent; all allergens in contact with the skin, Good- Skin contact acceptable; some tape edges lifting; all allergens in contact with the skin, Poor- Little to no skin contact with panel; one or more allergens not in contact with the skin, Detached- Panel completely off the skin; none of the allergens in contact with the skin	Day 2, visit 2 prior to panel removal
Tape Irritation	Tape irritation was measured according to the following scale: None- No irritation, Weak- Faint to definite pink erythema, Moderate- Moderate erythema, definite redness, Strong- Severe erythema, very intense redness. Following visit 6, the Investigators rated tape irritation based on the overall trend observed at visits 2-6. Irritation at visit 2 that resolved by visit 3 was considered none. Skin under occlusion from an adhesive material would be expected to have minimal irritation shortly after the panel is removed. Irritation that persisted or increased in severity beyond visit 3 but resolved by the following visit would have been rated as irritant. An allergic response was considered if irritation persisted beyond visit 3, increased in severity and had symptoms consistent with criteria used to score positive skin reactions according to standard patch testing guidelines established by the International Contact Dermatitis Research Group.	Visit 2 (day 2), visit 3 (day 3-4), visit 4 (day 7-8) visit 5 (day 10-14), visit 6 (day 19-23) with overall assessment by the Investigator following visit 6
Chip Irritation	Chip irritation was measured according to the following scale: None- No irritation, Weak- Faint to definite pink erythema, Moderate- Moderate erythema, definite redness, Strong- Severe erythema, very intense redness. Following visit 6, the Investigators rated Chip irritation based on the overall trend observed at visits 2-6. Irritation at visit 2 that resolved by visit 3 was considered none. Skin under occlusion from an adhesive material would be expected to have minimal irritation shortly after the panel is removed. Irritation that persisted or increased in severity beyond visit 3 but resolved by the following visit would have been rated as irritant. An allergic response was considered if irritation persisted beyond visit 3, increased in severity and had symptoms consistent with criteria used to score positive skin reactions according to standard patch testing guidelines established by the International Contact Dermatitis Research Group.	Visit 2 (day 2), visit 3 (day 3-4), visit 4 (day 7-8) visit 5 (day 10-14), visit 6 (day 19-23) with overall assessment by the Investigator following visit 6

Collaborators and Investigators

• Sponsor: Allerderm
• Investigators: Principal Investigator: Patricia L Norris, MD, Oregon Health & Science University, Portland USA; Principal Investigator: Karin Pacheco, MD, National Jewish Health School of Medicine, Colorado USA; Principal Investigator: Andreas Bircher, MD, University Hospital, Basel, Switzerland; Principal Investigator: Paolo Pigatto, MD, University of Milano, Italy; Principal Investigator: Thomas Rustemeyer, MD, PhD, VU University Medical Center, Netherlands; Principal Investigator: Peter Thomas, MD, Ludwig-Maximilians-Universität München, Germany; Principal Investigator: Maki Hosoki, DDS, PhD, Tokushima University Graduate School, Japan; Principal Investigator: Risa Tamagawa-Mineoka, MD, Kyoto Prefectural University of Medicine, Japan; Principal Investigator: Akiko Yagami, MD, PhD, Fujita Health University School of Medicine, Japan

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2016
• Primary Completion (Actual): July 15, 2019
• Study Completion (Actual): July 15, 2019

Study Registration Dates

• First Submitted: November 23, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimate): November 26, 2015

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 12, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Eczematous; Dermatitis; Eczema
• Other Study ID Numbers: SP148MP201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No