To evaluate the safety and efficacy of multiple doses of ABT-494 (Upadacitinib) monotherapy versus placebo in the treatment of adults with moderate to severe atopic dermatitis.
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Mean percent (%) change from Baseline (Day 1) in EASI score at Week 16.
Secondary outcome
• Proportion of subjects achieving an EASI 75 response, defined as at
least a 75% reduction in EASI score, at Week 16 relative to the Baseline
(Day 1)
• Proportion of subjects achieving an Investigator Global Assessment
(IGA) of 0 or 1 at Week 16
• Percent change from Baseline to Weeks 2, 8 and 16 in pruritus
numerical rating scale (NRS)
• Percent change in EASI score from Baseline at Week 8
• Proportion of subjects achieving EASI 50/75/90 response at Weeks 8
and 16
• Proportion of subjects achieving SCORAD 50/75/90 response at Weeks
8 and 16
• Proportion of subjects with Dermatology Life Quality Index (DLQI) =
"0" or "1" at Weeks 8 and 16
• Change from Baseline in DLQI at Weeks 8 and 16
Background summary
Atopic Dermatitis (AD; also known as atopic eczema) is an inflammatory,
pruritic, chronic or chronically relapsing skin disease. Treatment of AD in
adult patients depends on the extent and severity of disease. At this time
there is only one EMA-approved systemic treatment (cyclosporin A) for AD. Thus,
there is a high unmet need for a significant number of patients with an
inadequate response to topical agents. Evidence suggests that inhibition of
Janus kinase (JAK)-mediated pathways may be a promising approach for the
treatment of patients with moderate to severe AD. AbbVie is developing a small
molecule inhibitor of JAK, ABT-494 (Upadacitinib), that may address the
current needs.
Study objective
To evaluate the safety and efficacy of multiple doses of ABT-494
(Upadacitinib) monotherapy versus placebo in the treatment of adults with
moderate to severe atopic dermatitis.
Study design
In Period 1, subjects will be randomized in a 1:1:1:1 ratio to one of four
treatment groups:
(1) ABT-494 low dose, (2) ABT-494 medium dose, (3) ABT-494 high dose, (4)
matching placebo, for 16 weeks.
Subjects who complete Period 1 will be re-randomized at Week 16 within their
original treatment group assignments to either ABT-494 or placebo into a
72-week double-blind, placebo controlled treatment period (Period 2) in a 1:1
ratio. At the Week 16 visit, all subjects will be re-randomized as follows into
Period 2:
•*Subjects from Group 1 in Period 1: ABT-494 low dose or matching placebo for
72 weeks
•*Subjects from Group 2 in Period 1: ABT-494 medium dose or matching placebo
for 72 weeks
•*Subjects from Group 3 in Period 1: ABT-494 high dose or matching placebo for
72 weeks
•*Subjects from Group 4 in Period 1: ABT-494 high dose or matching placebo for
72 weeks
In order to minimize missing data for efficacy and safety assessments, subjects
who prematurely discontinue study drug treatment should continue to be followed
for all regularly scheduled visits, unless they have decided to discontinue the
study participation entirely (withdrawal of informed consent).
Intervention
Subjects will take once daily one tablet of ABT-494 (Upadacitinib) (low dose,
medium dose or high dose), or matching placebo for 88 weeks.
Study burden and risks
There will be higher burden for subjects participating in this trial compared
to their standard of care. Subject will be visiting the hospital more
frequently. During these visits study procedures will be performed including
blood sampling and questionnaires. Subject will also be tested for TB,
significant heart conditions, pregnancy, HCV/HBV and HIV. Subjects will also
complete a daily diary and questionnaire. During rest and sleep subjects will
wear an activity recording bracelet. Women of Childbearing Potential should
practice a method of birth control, during the study through at least 30 days
after the last dose of study drug. If male, subjects must practice
contraception during the study through at least 90 days after last dose of
study drug.
Subjects will either receive ABT-494 (Upadacitinib) or placebo during the
study. The most common side effects reported during previous studies of
ABT-494 (Upadacitinib) were headache, upper chest infection, common cold, back
pain, diarrhea and cough. An elevation of an enzyme in the blood called
creatine phosphokinase (CPK, a protein released mainly from muscle cells) was
observed in treated patients. Safety monitoring will be done during the study.
The hypothesis that ABT-494 (Upadacitinib) should be effective in targeting
inflammation and itch associated with AD and the lack of approved systemic
therapies for moderate to severe AD, especially for long-term use, indicate
that there is an acceptable rationale to conduct this study. The risks and
burden associated with participating in this study are acceptable in regards to
the potential benefit study subjects could possibly have.
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
Inclusion criteria
• Adult male or female, >= 18 and <= 75 years old at Screening.;• Atopic dermatitis with a diagnosis confirmed by a dermatologist (according to the Hanifin and Rajka criteria) and also onset of symptoms at least 1 year prior to baseline.;• Moderate to severe atopic dermatitis defined by an EASI >= 16, BSA >= 10% and an IGA score >= 3 at the Baseline visit.;• Documented history (within 1 year prior to the screening visit) of inadequate response to treatment with topical corticosteroids (TCS), or topical calcineurin inhibitors (TCI), or for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).;• Twice daily use of an additive-free, bland emollient for at least 7 days prior to Baseline.
Exclusion criteria
• Prior exposure to any systemic or topical JAK inhibitor (including but not limited to tofacitinib, baricitinib, ruxolitinib, and filgotinib).;• Treatment with topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin within 10 days prior to the Baseline visit.;• Prior exposure to dupilumab.;• Prior exposure to any investigational systemic treatment within 30 days or 5 half-lives (whichever is longer) of the Baseline visit or is currently enrolled in another clinical study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-002451-21-NL |
| ClinicalTrials.gov | NCT02925117 |
| CCMO | NL59149.018.16 |