Ignite Creation Date:
2024-05-06 @ 8:36 AM
Last Modification Date:
2024-10-26 @ 12:02 PM
Study NCT ID:
NCT02778711
Status:
UNKNOWN
Last Update Posted:
2016-05-20
First Post:
2016-05-04
Brief Title:
Anti-IL-17 a New Treatment for Contact Dermatititis
Sponsor:
Tanja Todberg MD
Organization:
University of Copenhagen
Study Overview
Official Title:
Anti-IL-17 a New Treatment for Contact Dermatititis
Status:
UNKNOWN
Status Verified Date:
2016-05
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to assess the efficacy of anti-IL 17 treatment secukinumab in patients with known severe allergic contact dermatitis ACD
Detailed Description:
Purpose The purpose of this study is to assess the efficacy of anti-IL 17 treatment secukinumab in patients with known severe allergic contact dermatitis ACD
Background ACD is an immune mediated disease characterized by itching erythema vesicles thickening and scaly skin affecting a large part of the population in the world A review study from 2007 by Thyssen et al that summarizes studies from North Europe and North America from 1966-2007 suggests that the prevalence to at least one allergen among these populations was 212 range 125-4061 The incidence of ACD is not static and differs in countries1 but in recent years there has been an increasing incidence of ACD caused by an increasing number of environmental detergents2 3 For patients with severe ACD the disease can be associated with difficulties performing daily activities loss of sleep and reduced life quality DLQI4
ACD is treated with moisturizing creams topical steroids and in severe cases systemic steroids UVB PUVA azathioprin or alitretinoin However the drugs have severe side effects and some patients with ACD do not respond to the already existing treatments New treatments are therefore highly needed A group of these patients suffer from severe eczema often resulting in impared lifestyle and not seldom loss of work4
The pathogenesis in ACD is a T-cell mediated delayed type hypersensitivity reaction consisting of a sensitization and an elicitation phase 5 In the sensitization phase an exogen allergenhapten is entering the epidermis through a defect skin barrier The allergen is presented by the Langerhans cells to CD4 and CD8 T-cells in the lymphatic nodes which activates and increases the numbers of T-cells The elicitations phase begins when the patient once again is in contact with the allergen The T-cells react with the allergen and this releases cytokines such as IFN-ɣ followed by skin lesions and inflammation The IFN-ɣ is an important inflammatory cytokine which is produced by CD4 and CD8 T-cells during ACD in humans and mice6 7 However in the last decades studies have revealed that other inflammatory cytokines such as IL-17 and IL-22 may be of importance in the immune response to contact allergens8-11 IL-17 is produced by T-helper TH17 cells innate cells as macrophages and dendrit cells and other cell types12
In mice both CD4 and CD8 T-cells producing IL-17 have been identified13 A study by Nakae et al where IL-17 deficient mice were generated and exposed to dinitroflorobenzene and trinitrochlorobenzene the mutants had a markedly reduced ear swelling compared to wild-type mice this suggesting that IL-17 plays a role in contact allergy 14
In nickel allergic humans CD4 and CD8 T-cells have been shown to produce IL-17 and an increasing number of IL-17 producing cells have been found in tissue with eczematous reaction8 Our group and others have found nickel-specific Th1 and Th17 cells in individuals with nickel allergy but not in healthy controls8 9
Our hypothesis is that since IL-17 appears to be involved in human ACD anti-IL-17 treatment secukinumab might have a beneficial effect in patients with ACD
This study will evaluate secukinumab treatment in patients with known allergic contact dermatitis The study which is an interventional type will consist of two parts both performed at Department of Dermato-allergology Herlev and Gentofte Hospital University of Copenhagen Hellerup Denmark
Study 1 Study 1 will include 10 patients with known allergy to nickel but with no to low grade of eczema at inclusion
Before enrollment patients will be screened for eligibility blood samples 8-10 ml Quantiferon TB Gold test urine test for infectionpregnancy and chest x-ray to ensure that there is no evidence of infections andor malignancy15
The patients will then be tested with two standard patch tests with nickel and vehicle at the upper inner arm to confirm allergy A photo and a biopsy 4 mm from the patch test area will be taken a clinical examination and a skinfold measure to evaluate the grade of dermatitis will be performed The responses will be assessed clinically at 48 h 72 h and day 7 after application and graded as negative - doubtful 1 2 3 or 4 using a modified version of the International Contact Dermatitis Research ICDRG scoring system
Patients will receive 300 mg secukinumab for sc injection autoinjector as a single dose administered by a nurse at Department of Dermato-allergology Gentofte Hospital After one week the patients will be retested with nickel photos and a biopsy from the patch test area will be taken a clinical examination and a skinfold measure will be performed to evaluate the efficacy of secukinumab
The study comprises 8 visits in total including screening
Study 2 Study 2 will include 10 patients with more than two known allergic contact allergies and clinically moderate to severe PGA3 allergic contact dermatitis at inclusion Patients will be treated open labeled for 8 weeks
Before enrollment patients will be screened for eligibility blood samples 20-25 ml Quantiferon TB Gold test urine test for infectionpregnancy and chest x-ray to ensure that there is no evidence of infections andor malignancy15 Clinical degree of dermatitis will be evaluated by using Physician Global Assessment score PGA as an instrument for the severity of eczema with the following PGA levels clear almost clear mild moderate severe Dermatology Life Quality Index DLQI appendix 1 and Patients Global Assessment score PtGA appendix 2 will be measured and photos of the eczema will be taken
When test results from baseline clinical procedures are ready 7-14 days from screening visit patients eligible for inclusion will have a biopsy taken 4 mm at eczema PGA PtGA and DLQI will be performed and photos of eczema will be taken This will be considered as baseline Afterwards treatment with 300 mg secukinumab for sc injection autoinjector will initiate with the first dose administered by a nurse at Department of Dermato-allergology Gentofte Hospital During the first four weeks patients will be treated with secukinumab once a week After this period secukinumab will be administered once a month with last dose given at week 8 All doses of secukinumab besides the first dose will be self-administered by the patients
Two and four weeks from baseline another biopsy will be taken PGA PtGA and DLQI will be performed and photos of eczema will be taken to evaluate the efficacy of secukinumab At week 4 another blood sample 12 ml will be taken cytokine level IFN-ɣ and IL-17 will be evaluated Eight and twelve weeks from baseline PGA PtGA and DLQI will be performed and photos will be taken to evaluate the efficacy of secukinumab A follow up visit will be performed 16 weeks from baseline where relapse PGA PtGA DLQI and safety during the treatment free weeks will be explored
The study comprises 7 visits in total including screening
Background ACD is an immune mediated disease characterized by itching erythema vesicles thickening and scaly skin affecting a large part of the population in the world A review study from 2007 by Thyssen et al that summarizes studies from North Europe and North America from 1966-2007 suggests that the prevalence to at least one allergen among these populations was 212 range 125-4061 The incidence of ACD is not static and differs in countries1 but in recent years there has been an increasing incidence of ACD caused by an increasing number of environmental detergents2 3 For patients with severe ACD the disease can be associated with difficulties performing daily activities loss of sleep and reduced life quality DLQI4
ACD is treated with moisturizing creams topical steroids and in severe cases systemic steroids UVB PUVA azathioprin or alitretinoin However the drugs have severe side effects and some patients with ACD do not respond to the already existing treatments New treatments are therefore highly needed A group of these patients suffer from severe eczema often resulting in impared lifestyle and not seldom loss of work4
The pathogenesis in ACD is a T-cell mediated delayed type hypersensitivity reaction consisting of a sensitization and an elicitation phase 5 In the sensitization phase an exogen allergenhapten is entering the epidermis through a defect skin barrier The allergen is presented by the Langerhans cells to CD4 and CD8 T-cells in the lymphatic nodes which activates and increases the numbers of T-cells The elicitations phase begins when the patient once again is in contact with the allergen The T-cells react with the allergen and this releases cytokines such as IFN-ɣ followed by skin lesions and inflammation The IFN-ɣ is an important inflammatory cytokine which is produced by CD4 and CD8 T-cells during ACD in humans and mice6 7 However in the last decades studies have revealed that other inflammatory cytokines such as IL-17 and IL-22 may be of importance in the immune response to contact allergens8-11 IL-17 is produced by T-helper TH17 cells innate cells as macrophages and dendrit cells and other cell types12
In mice both CD4 and CD8 T-cells producing IL-17 have been identified13 A study by Nakae et al where IL-17 deficient mice were generated and exposed to dinitroflorobenzene and trinitrochlorobenzene the mutants had a markedly reduced ear swelling compared to wild-type mice this suggesting that IL-17 plays a role in contact allergy 14
In nickel allergic humans CD4 and CD8 T-cells have been shown to produce IL-17 and an increasing number of IL-17 producing cells have been found in tissue with eczematous reaction8 Our group and others have found nickel-specific Th1 and Th17 cells in individuals with nickel allergy but not in healthy controls8 9
Our hypothesis is that since IL-17 appears to be involved in human ACD anti-IL-17 treatment secukinumab might have a beneficial effect in patients with ACD
This study will evaluate secukinumab treatment in patients with known allergic contact dermatitis The study which is an interventional type will consist of two parts both performed at Department of Dermato-allergology Herlev and Gentofte Hospital University of Copenhagen Hellerup Denmark
Study 1 Study 1 will include 10 patients with known allergy to nickel but with no to low grade of eczema at inclusion
Before enrollment patients will be screened for eligibility blood samples 8-10 ml Quantiferon TB Gold test urine test for infectionpregnancy and chest x-ray to ensure that there is no evidence of infections andor malignancy15
The patients will then be tested with two standard patch tests with nickel and vehicle at the upper inner arm to confirm allergy A photo and a biopsy 4 mm from the patch test area will be taken a clinical examination and a skinfold measure to evaluate the grade of dermatitis will be performed The responses will be assessed clinically at 48 h 72 h and day 7 after application and graded as negative - doubtful 1 2 3 or 4 using a modified version of the International Contact Dermatitis Research ICDRG scoring system
Patients will receive 300 mg secukinumab for sc injection autoinjector as a single dose administered by a nurse at Department of Dermato-allergology Gentofte Hospital After one week the patients will be retested with nickel photos and a biopsy from the patch test area will be taken a clinical examination and a skinfold measure will be performed to evaluate the efficacy of secukinumab
The study comprises 8 visits in total including screening
Study 2 Study 2 will include 10 patients with more than two known allergic contact allergies and clinically moderate to severe PGA3 allergic contact dermatitis at inclusion Patients will be treated open labeled for 8 weeks
Before enrollment patients will be screened for eligibility blood samples 20-25 ml Quantiferon TB Gold test urine test for infectionpregnancy and chest x-ray to ensure that there is no evidence of infections andor malignancy15 Clinical degree of dermatitis will be evaluated by using Physician Global Assessment score PGA as an instrument for the severity of eczema with the following PGA levels clear almost clear mild moderate severe Dermatology Life Quality Index DLQI appendix 1 and Patients Global Assessment score PtGA appendix 2 will be measured and photos of the eczema will be taken
When test results from baseline clinical procedures are ready 7-14 days from screening visit patients eligible for inclusion will have a biopsy taken 4 mm at eczema PGA PtGA and DLQI will be performed and photos of eczema will be taken This will be considered as baseline Afterwards treatment with 300 mg secukinumab for sc injection autoinjector will initiate with the first dose administered by a nurse at Department of Dermato-allergology Gentofte Hospital During the first four weeks patients will be treated with secukinumab once a week After this period secukinumab will be administered once a month with last dose given at week 8 All doses of secukinumab besides the first dose will be self-administered by the patients
Two and four weeks from baseline another biopsy will be taken PGA PtGA and DLQI will be performed and photos of eczema will be taken to evaluate the efficacy of secukinumab At week 4 another blood sample 12 ml will be taken cytokine level IFN-ɣ and IL-17 will be evaluated Eight and twelve weeks from baseline PGA PtGA and DLQI will be performed and photos will be taken to evaluate the efficacy of secukinumab A follow up visit will be performed 16 weeks from baseline where relapse PGA PtGA DLQI and safety during the treatment free weeks will be explored
The study comprises 7 visits in total including screening
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None