To Assess the Safety and Activity of GBR 830, Compared to Placebo, in Adults With Moderate-to-severe Atopic Dermatitis
- Conditions
- Atopic Dermatitis
- Interventions
- Biological: GBR 830Biological: Placebo
- Registration Number
- NCT02683928
- Lead Sponsor
- Ichnos Sciences SA
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- Male or female, 18 years or older
- Atopic dermatitis involvement that of at least 10% body surface area
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GBR 830 GBR 830 Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart. Placebo Placebo Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart.
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events 16 weeks 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 Day 1, before dosing (baseline), and Day 29 and Day 71, after dosing. 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 71 days Ratio of post-baseline/baseline value of messenger ribonucleic acid (mRNA) expression in lesional skin biopsies is reported.
- Secondary Outcome Measures
Name Time Method Percent Change in Eczema Area and Severity Index (EASI) Clinical Scores From Baseline Day 4, Day 29, Day 57, Day 71 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 Day 4, Day 29, Day 57, Day 71 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. 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 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. 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 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 Samples collected for immunogenicity analysis at Baseline (pre-dose), and at Day 15, Day 29 (pre-dose), Day 57, and Day 85. 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.
Trial Locations
- Locations (17)
Glenmark Investigational Site 5
🇺🇸Los Angeles, California, United States
Glenmark Investigational Site 14
🇺🇸Rogers, Arkansas, United States
Glenmark Investigational Site 15
🇺🇸Tampa, Florida, United States
Glenmark Investigational Site 3
🇺🇸San Diego, California, United States
Glenmark Investigational Site 11
🇺🇸Saint Louis, Missouri, United States
Glenmark Investigational Site 16
🇺🇸Berlin, New Jersey, United States
Glenmark Investigational Site 1
🇺🇸New York, New York, United States
Glenmark Investigational Site 9
🇺🇸Raleigh, North Carolina, United States
Glenmark Investigational Site 2
🇺🇸Dallas, Texas, United States
Glenmark Investigational Site 12
🇺🇸Webster, Texas, United States
Glenmark Investigational Site 17
🇺🇸Katy, Texas, United States
Glenmark Investigational Site 8
🇨🇦Markham, Ontario, Canada
Glenmark Investigational Site 6
🇨🇦Richmond Hill, Ontario, Canada
Glenmark Investigational Site 7
🇨🇦Peterborough, Ontario, Canada
Glenmark Investigational Site 10
🇨🇦Waterloo, Ontario, Canada
Glenmark Investigational Site 4
🇨🇦Montreal, Quebec, Canada
Glenmark Investigational Site 13
🇺🇸Fairborn, Ohio, United States