Angioedema, Chronic Idiopathic Urticaria, Chronic Spontaneous Urticaria, Hives, Pruritis, Urticaria
Conditions
Brief summary
This study is being conducted to evaluate the efficacy and safety of povorcitinib in adults with CSU that is inadequately controlled using SOC treatments.
Interventions
DRUGPovorcitinib
oral; tablet
DRUGPlacebo
oral; tablet
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply: * CSU diagnosis for ≥ 3 months prior to screening. * CSU refractory to second-generation H1 antihistamines * Participants must have been on a stable dose of second-generation H1 antihistamine, and must agree to maintain the stable dose of second-generation H1 antihistamine throughout study. * Willingness and ability to comply with the study Protocol and procedures. * Further inclusion criteria apply
Exclusion criteria
* Treatment with an anti-IgE biologic (eg, omalizumab) within 8 weeks prior to screening. * Clearly defined underlying etiology for chronic urticarias other than CSU * Other cutaneous or systemic diseases with chronic itching or with symptoms of urticaria or angioedema. * Women who are pregnant (or who are considering pregnancy) or breastfeeding. * Concurrent or history of Thrombocytopenia, coagulopathy, or platelet dysfunction, Venous and arterial thrombosis, deep vein thrombosis, pulmonary embolism, stroke, moderate to severe heart failure (NYHA Class III or IV), cerebrovascular accident, MI, coronary stenting, or CABG surgery, other significant cardiovascular diseases or uncontrolled hypertension * Recipient of an organ transplant that requires continued immunosuppression. * Any malignancies or history of malignancies with the exception of adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ. * Chronic or recurrent infectious disease. * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Week 12 | Baseline; Week 12 | The UAS7 is defined as the 7-day sum of the individual, daily recorded scores for the hive severity score (HSS) and the itch severity score (ISS). The ISS7 is defined as the 7-day sum of the daily ISS scores (ranging from 0 to 3), and the HSS7 is defined as the 7-day sum of the daily HSS scores (ranging from 0 to 3). The UAS7 score is calculated as the sum of the available UAS scores, divided by the number of days that have a UAS score, multiplied by 7. The UAS7 (ranging from 0 to 42) is equal to the ISS7 (ranging from 0 to 21) plus the HSS7 (ranging from 0 to 21). Higher scores represent more intense/severe hives and itching. Change from baseline was calculated as the post-baseline value minus the baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved UAS7 ≤ 6 (Controlled Disease) at Week 12 | Week 12 | The UAS7 is defined as the 7-day sum of the individual, daily recorded scores for the HSS and the ISS. The ISS7 is defined as the 7-day sum of the daily ISS scores (ranging from 0 to 3), and the HSS7 is defined as the 7-day sum of the daily HSS scores (ranging from 0 to 3). The UAS7 score is calculated as the sum of the available UAS scores, divided by the number of days that have a UAS score, multiplied by 7. The UAS7 (ranging from 0 to 42) is equal to the ISS7 (ranging from 0 to 21) plus the HSS7 (ranging from 0 to 21). Higher scores represent more intense/severe hives and itching. |
| Time to First Achievement of UAS7 ≤ 6 (Controlled Disease) During the Placebo-controlled (PC) Period | up to Week 12 | The UAS7 is defined as the 7-day sum of the individual, daily recorded scores for the HSS and the ISS. The ISS7 is defined as the 7-day sum of the daily ISS scores (ranging from 0 to 3), and the HSS7 is defined as the 7-day sum of the daily HSS scores (ranging from 0 to 3). The UAS7 score is calculated as the sum of the available UAS scores, divided by the number of days that have a UAS score, multiplied by 7. The UAS7 (ranging from 0 to 42) is equal to the ISS7 (ranging from 0 to 21) plus the HSS7 (ranging from 0 to 21). Higher scores represent more intense/severe hives and itching. |
| Percentage of Participants With UAS7 = 0 at Week 12 | Week 12 | The UAS7 is defined as the 7-day sum of the individual, daily recorded scores for the HSS and the ISS. The ISS7 is defined as the 7-day sum of the daily ISS scores (ranging from 0 to 3), and the HSS7 is defined as the 7-day sum of the daily HSS scores (ranging from 0 to 3). The UAS7 (ranging from 0 to 42) is equal to the ISS7 (ranging from 0 to 21) plus the HSS7 (ranging from 0 to 21). Higher scores represent more intense/severe hives and itching. |
| Placebo-controlled Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to Week 12 | An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as an AE reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 60 days after the last dose of study drug. |
| Extension Period: Number of Participants With Any TEAE | from Week 12 to Week 44 | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as an AE reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 60 days after the last dose of study drug. |
Countries
Germany, Poland, United States
Participant flow
Pre-assignment details
This study was conducted in 35 sites in Germany, Poland, and the United States.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 11.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 120 Participants |
| Sex: Female, Male Female | 109 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 33 | 0 / 34 | 1 / 35 | 0 / 9 | 0 / 7 | 0 / 10 | 0 / 29 | 0 / 30 | 1 / 32 |
| other Total, other adverse events | 8 / 34 | 10 / 33 | 12 / 34 | 17 / 35 | 5 / 9 | 5 / 7 | 4 / 10 | 14 / 29 | 16 / 30 | 17 / 32 |
| serious Total, serious adverse events | 3 / 34 | 0 / 33 | 0 / 34 | 0 / 35 | 0 / 9 | 0 / 7 | 0 / 10 | 0 / 29 | 0 / 30 | 1 / 32 |
Outcome results
None listed