Atopic Dermatitis, Pruritus
Conditions
Keywords
Atopic Dermatitis, Pruritus, CR845, Chronic Itch, difelikefalin, Itch, Itching, Generalized pruritus, Eczema
Brief summary
This is a two-part, multicenter, randomized, double-blind study to evaluate the efficacy and safety of oral difelikefalin as adjunct therapy to a topical corticosteroid (TCS) for moderate-to-severe pruritus in adult subjects with atopic dermatitis (AD).
Detailed description
Part A of this study includes a 12-week Double-blind Treatment Period and a 52-week Open-label Extension Period. Subjects will be randomized to receive oral difelikefalin 0.25 mg tablets BID plus TCS cream, difelikefalin 0.5 mg tablets BID plus TCS cream, placebo tablets BID plus TCS cream or placebo tablets BID plus vehicle cream. Part B of this study includes a 12-week Double-blind Treatment Period and 52-week Open-label Extension Period. Subjects will be randomized to receive oral difelikefalin 0.25 mg or 0.5 mg tablets BID plus TCS cream or oral placebo tablets BID plus TCS cream. Part A results at week 12 will inform Part B. Subjects who participated in Part A of the study may not participate in Part B. All subjects will sign an informed consent form (ICF) and undergo screening for study eligibility.
Interventions
Oral difelikefalin 0.25 mg tablets administered twice daily
Oral difelikefalin 0.5 mg tablets administered twice daily
DRUGTCS Cream
TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed
DRUGPlacebo
Oral Placebo tablets administered twice daily
DRUGVehicle Cream
Vehicle Cream applied by study subjects to skin lesions once a day until control is achieved, then as needed
Sponsors
Cara Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Part A includes 4 arms and Part B includes 2 arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: To be eligible for inclusion into the study, a patient must meet the following criteria: * Subject has clinically confirmed diagnosis of active AD; * Subject has chronic pruritus related to AD; * Subject has moderate to severe pruritus; * Female subject is not pregnant or nursing during any period of the study. Key
Exclusion criteria
A patient will be excluded from the study if any of the following criteria are met: * Subject has clinically infected AD; * Subject has pruritus attributed to a cause other than AD; * Subject has any clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients achieving an improvement from baseline ≥4 points with respect to the weekly mean of the daily 24-hour I-NRS score at Week 12 | Week 12 |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with ≥ 3 point improvement from baseline in the weekly mean of the daily 24-hour Sleep Disturbance NRS score at the end of Week 12 (among subjects with a Sleep Disturbance NRS score of > 3 at baseline) | Week 12 |
| Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 2 | Week 2 |
| Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 1 | Week 1 |
| Mean change and mean percent change from baseline in EASI score at Week 12. | Week 12 |
| Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 4 | Week 4 |
| Proportion of subjects achieving a vIGA-ADTM score of clear (0) or almost clear (1) with a 2-point improvement from baseline at Week 12 (among subjects with a vIGA-ADTM score ≥ 2 at Day 1) | Week 12 |
| Proportion of subjects achieving at least ≥ 3-point improvement in the Skin Pain NRS score at Week 12 (among subjects with a Skin Pain NRS score > 3 at Day 1) | Week 12 |
| Proportion of subjects with ≥ 4 point improvement from baseline in Dermatology Life Quality Index (DLQI) score at Week 12 (among subjects with DLQI score > 4 at baseline) | Week 12 |
| Proportion of subjects achieving a vIGA-ADTM score of clear (0) or almost clear (1) with a 2-point improvement from baseline at Week 12 (among subjects with a vIGA-ADTM score ≥ 3 at Day 1) | Week 12 |
Countries
United States
Outcome results
None listed