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To Assess the Safety and Activity of GBR 830, Compared to Placebo, in Adults With Moderate-to-severe Atopic Dermatitis

Primary Purpose

Atopic Dermatitis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GBR 830
Placebo
Sponsored by
Ichnos Sciences SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atopic Dermatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female, 18 years or older
  • Atopic dermatitis involvement that of at least 10% body surface area

Exclusion Criteria:

  • Treatment with systemic corticosteroids within 4 weeks before randomization, and topical steroids, tacrolimus and/or pimecrolimus within 1 week before the randomization (except emollients, and mild steroids (class 6 or 7)
  • Any cell-depleting agents including but not limited to rituximab: within 6 months prior to the baseline visit or until lymphocyte and CD 19+ lymphocyte counts return to normal, whichever is longer. Other biologics: within 5 half-lives or 8 weeks prior to the baseline visit, whichever is longer. Allergen immunotherapy within 6 months before the baseline visit.
  • Patient with history of serious local infection and systemic infection Patient with history or current evidence of diseases such as tuberculosis, malignant disease, other inflammatory or autoimmune disease or HIV or Hepatitis B or C positive.

Sites / Locations

  • Glenmark Investigational Site 14
  • Glenmark Investigational Site 5
  • Glenmark Investigational Site 3
  • Glenmark Investigational Site 15
  • Glenmark Investigational Site 11
  • Glenmark Investigational Site 16
  • Glenmark Investigational Site 1
  • Glenmark Investigational Site 9
  • Glenmark Investigational Site 13
  • Glenmark Investigational Site 2
  • Glenmark Investigational Site 17
  • Glenmark Investigational Site 12
  • Glenmark Investigational Site 8
  • Glenmark Investigational Site 7
  • Glenmark Investigational Site 6
  • Glenmark Investigational Site 10
  • Glenmark Investigational Site 4

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

GBR 830

Placebo

Arm Description

Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart.

Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart.

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events
A treatment-emergent adverse event (TEAE) was defined as any new adverse event (AEs) or worsening of an existing condition after administration of the study drug up to and including the follow-up visit.
Change From Baseline in Thickness of Lesional Skin Biopsies
Epidermal thickness was assessed in Hematoxylin and Eosin stained sections of lesional skin biopsies on Day 1 (baseline), Day 29, and Day 71.
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies
Ratio of post-baseline/baseline value of messenger ribonucleic acid (mRNA) expression in lesional skin biopsies is reported.

Secondary Outcome Measures

Percent Change in Eczema Area and Severity Index (EASI) Clinical Scores From Baseline
In EASI, four disease characteristics of atopic dermatitis (erythema, edema/papulation, excoriation, and lichenification) are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the four body regions (Head and neck, trunk, arms, and legs). The assigned percentages of body surface area (BSA) for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs, respectively. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin in that area: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.
Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Clinical Score of 0 or 1
The IGA is an assessment scale used in clinical studies to determine severity of AD based on a 5-point scale ranging from 0 (clear) to 4 (severe/very severe).
Pharmacokinetics of GBR 830 in Terms of Cmax After First and Second Dose.
Pharmacokinetics in terms of Cmax (maximum observed concentration after second [last] dosing interval) was estimated after the first and second dose.
Pharmacokinetics of GBR 830 in Terms of AUC0-tau After the First and Second Dose.
Pharmacokinetics in terms of AUC0-tau [Trapezoid calculation of area under the serum drug concentration-time curve from time zero (pre dose time point of the infusion) to the end of the dosing interval] was estimated.
Number of Participants Positive or Negative for Anti-drug Antibodies (ADA) to GBR 830 to Evaluate Immunogenicity
Blood samples were collected at time points to detect anti-drug antibodies (ADAs) to GBR 830, as per procedures similar to collection of PK samples. Antibodies of GBR 830 were detected and confirmed using a validated enzyme-linked immunosorbent assay (ELISA) method.

Full Information

First Posted
February 4, 2016
Last Updated
May 4, 2020
Sponsor
Ichnos Sciences SA
Collaborators
Glenmark Pharmaceuticals S.A.
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1. Study Identification

Unique Protocol Identification Number
NCT02683928
Brief Title
To Assess the Safety and Activity of GBR 830, Compared to Placebo, in Adults With Moderate-to-severe Atopic Dermatitis
Official Title
A Phase IIa, Double-Blind, Randomised, Placebo-controlled, Exploratory Study to Evaluate the Safety, Biological Activity and Pharmacokinetics of GBR 830 in Adults With Moderate-to-Severe Atopic Dermatitis
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ichnos Sciences SA
Collaborators
Glenmark Pharmaceuticals S.A.

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to determine the effect of GBR 830 on biomarkers in atopic dermatitis to enable further studies in this indication.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GBR 830
Arm Type
Experimental
Arm Description
Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart.
Intervention Type
Biological
Intervention Name(s)
GBR 830
Intervention Type
Biological
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
A treatment-emergent adverse event (TEAE) was defined as any new adverse event (AEs) or worsening of an existing condition after administration of the study drug up to and including the follow-up visit.
Time Frame
16 weeks
Title
Change From Baseline in Thickness of Lesional Skin Biopsies
Description
Epidermal thickness was assessed in Hematoxylin and Eosin stained sections of lesional skin biopsies on Day 1 (baseline), Day 29, and Day 71.
Time Frame
Day 1, before dosing (baseline), and Day 29 and Day 71, after dosing.
Title
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies
Description
Ratio of post-baseline/baseline value of messenger ribonucleic acid (mRNA) expression in lesional skin biopsies is reported.
Time Frame
71 days
Secondary Outcome Measure Information:
Title
Percent Change in Eczema Area and Severity Index (EASI) Clinical Scores From Baseline
Description
In EASI, four disease characteristics of atopic dermatitis (erythema, edema/papulation, excoriation, and lichenification) are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the four body regions (Head and neck, trunk, arms, and legs). The assigned percentages of body surface area (BSA) for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs, respectively. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin in that area: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.
Time Frame
Day 4, Day 29, Day 57, Day 71
Title
Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Clinical Score of 0 or 1
Description
The IGA is an assessment scale used in clinical studies to determine severity of AD based on a 5-point scale ranging from 0 (clear) to 4 (severe/very severe).
Time Frame
Day 4, Day 29, Day 57, Day 71
Title
Pharmacokinetics of GBR 830 in Terms of Cmax After First and Second Dose.
Description
Pharmacokinetics in terms of Cmax (maximum observed concentration after second [last] dosing interval) was estimated after the first and second dose.
Time Frame
Blood samples were collected on Day 1 and Day 29: pre-dose (15 mins), end of infusion (1 hour) and 1.5, 2, 72, and 504 hours post start of infusion
Title
Pharmacokinetics of GBR 830 in Terms of AUC0-tau After the First and Second Dose.
Description
Pharmacokinetics in terms of AUC0-tau [Trapezoid calculation of area under the serum drug concentration-time curve from time zero (pre dose time point of the infusion) to the end of the dosing interval] was estimated.
Time Frame
Blood samples were collected on Day 1 and Day 29: pre-dose (15 mins), end of infusion (1 hour) and 1.5, 2, 72, and 504 hours post start of infusion
Title
Number of Participants Positive or Negative for Anti-drug Antibodies (ADA) to GBR 830 to Evaluate Immunogenicity
Description
Blood samples were collected at time points to detect anti-drug antibodies (ADAs) to GBR 830, as per procedures similar to collection of PK samples. Antibodies of GBR 830 were detected and confirmed using a validated enzyme-linked immunosorbent assay (ELISA) method.
Time Frame
Samples collected for immunogenicity analysis at Baseline (pre-dose), and at Day 15, Day 29 (pre-dose), Day 57, and Day 85.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, 18 years or older Atopic dermatitis involvement that of at least 10% body surface area Exclusion Criteria: Treatment with systemic corticosteroids within 4 weeks before randomization, and topical steroids, tacrolimus and/or pimecrolimus within 1 week before the randomization (except emollients, and mild steroids (class 6 or 7) Any cell-depleting agents including but not limited to rituximab: within 6 months prior to the baseline visit or until lymphocyte and CD 19+ lymphocyte counts return to normal, whichever is longer. Other biologics: within 5 half-lives or 8 weeks prior to the baseline visit, whichever is longer. Allergen immunotherapy within 6 months before the baseline visit. Patient with history of serious local infection and systemic infection Patient with history or current evidence of diseases such as tuberculosis, malignant disease, other inflammatory or autoimmune disease or HIV or Hepatitis B or C positive.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerhard Wolff, MD
Organizational Affiliation
Glenmark Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Glenmark Investigational Site 14
City
Rogers
State/Province
Arkansas
ZIP/Postal Code
72759
Country
United States
Facility Name
Glenmark Investigational Site 5
City
Los Angeles
State/Province
California
ZIP/Postal Code
90045
Country
United States
Facility Name
Glenmark Investigational Site 3
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Glenmark Investigational Site 15
City
Tampa
State/Province
Florida
ZIP/Postal Code
33624
Country
United States
Facility Name
Glenmark Investigational Site 11
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63117
Country
United States
Facility Name
Glenmark Investigational Site 16
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
Glenmark Investigational Site 1
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Glenmark Investigational Site 9
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27612
Country
United States
Facility Name
Glenmark Investigational Site 13
City
Fairborn
State/Province
Ohio
ZIP/Postal Code
45324
Country
United States
Facility Name
Glenmark Investigational Site 2
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Glenmark Investigational Site 17
City
Katy
State/Province
Texas
ZIP/Postal Code
77494
Country
United States
Facility Name
Glenmark Investigational Site 12
City
Webster
State/Province
Texas
ZIP/Postal Code
77598
Country
United States
Facility Name
Glenmark Investigational Site 8
City
Markham
State/Province
Ontario
ZIP/Postal Code
L3P 1X2
Country
Canada
Facility Name
Glenmark Investigational Site 7
City
Peterborough
State/Province
Ontario
ZIP/Postal Code
K9J 5K2
Country
Canada
Facility Name
Glenmark Investigational Site 6
City
Richmond Hill
State/Province
Ontario
ZIP/Postal Code
L4C 9M7
Country
Canada
Facility Name
Glenmark Investigational Site 10
City
Waterloo
State/Province
Ontario
ZIP/Postal Code
N2J 1C4
Country
Canada
Facility Name
Glenmark Investigational Site 4
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2K 4L5
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
30738171
Citation
Guttman-Yassky E, Pavel AB, Zhou L, Estrada YD, Zhang N, Xu H, Peng X, Wen HC, Govas P, Gudi G, Ca V, Fang H, Salhi Y, Back J, Reddy V, Bissonnette R, Maari C, Grossman F, Wolff G. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J Allergy Clin Immunol. 2019 Aug;144(2):482-493.e7. doi: 10.1016/j.jaci.2018.11.053. Epub 2019 Feb 6.
Results Reference
result

Learn more about this trial

To Assess the Safety and Activity of GBR 830, Compared to Placebo, in Adults With Moderate-to-severe Atopic Dermatitis

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