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

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02683928
• Other study ID #: GBR 830-201
• Status: Completed
• Phase: Phase 2
• Start date: March 2016
• Est. completion date: June 2017

Study information

• Verified date: May 2020
• Source: Ichnos Sciences SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Biological:
• GBR 830

• Placebo

Locations

Country	Name	City	State
Canada	Glenmark Investigational Site 8	Markham	Ontario
Canada	Glenmark Investigational Site 4	Montreal	Quebec
Canada	Glenmark Investigational Site 7	Peterborough	Ontario
Canada	Glenmark Investigational Site 6	Richmond Hill	Ontario
Canada	Glenmark Investigational Site 10	Waterloo	Ontario
United States	Glenmark Investigational Site 16	Berlin	New Jersey
United States	Glenmark Investigational Site 2	Dallas	Texas
United States	Glenmark Investigational Site 13	Fairborn	Ohio
United States	Glenmark Investigational Site 17	Katy	Texas
United States	Glenmark Investigational Site 5	Los Angeles	California
United States	Glenmark Investigational Site 1	New York	New York
United States	Glenmark Investigational Site 9	Raleigh	North Carolina
United States	Glenmark Investigational Site 14	Rogers	Arkansas
United States	Glenmark Investigational Site 11	Saint Louis	Missouri
United States	Glenmark Investigational Site 3	San Diego	California
United States	Glenmark Investigational Site 15	Tampa	Florida
United States	Glenmark Investigational Site 12	Webster	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Ichnos Sciences SA	Glenmark Pharmaceuticals S.A.

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 i — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	16 weeks
Primary	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.	Day 1, before dosing (baseline), and Day 29 and Day 71, after dosing.
Primary	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.	71 days
Secondary	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.	Day 4, Day 29, Day 57, Day 71
Secondary	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).	Day 4, Day 29, Day 57, Day 71
Secondary	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.	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
Secondary	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.	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
Secondary	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.	Samples collected for immunogenicity analysis at Baseline (pre-dose), and at Day 15, Day 29 (pre-dose), Day 57, and Day 85.