Chronic Spontaneous Urticaria
Conditions
Brief summary
This is an exploratory study designed to generate preliminary data in evaluating the efficacy of Nucala in the treatment of chronic spontaneous urticaria.
Detailed description
This is an open-label, single arm exploratory study of mepolizumab in the treatment of CSU. The primary endpoint will be the mean reduction in the seven day urticaria activity score (UAS7) before and after 10 weeks of treatment with mepolizumab. Secondary endpoints will be the mean reduction of the urticaria control test (UCT) score and the weekly itch severity score (ISS) before and after treatment. Enrollment examination will include a standardized history and examination, baseline UCT score, CBC with differential, serum IgE level, chronic urticaria index, IgE Fc receptor antibody functional assay, and a 4 mm punch biopsy of lesional skin to confirm the urticarial tissue reaction includes eosinophils and is not neutrophilic predominant. Patients will discontinue all anti-histamines and start cetirizine 10 mg PO BID which may be continued throughout the study duration. Patients will be provided with a log book to track daily urticaria signs and symptoms in a standardized manner for UAS scoring. At week 0 (enrollment visit +7 days), baseline UAS7 and ISS score will be assessed and skin biopsy results reviewed. Patients with a confirmatory skin biopsy will receive 200 mg SC of mepolizumab at week 0,2,4,6,and 8. UAS-7 and weekly ISS score will be calculated at week 0, 4, 8, and 10. UCT scoring will be calculated at week 0 and at week 10. Repeat CBC with differential, serum IgE level, and measures of basophil serum activation (chronic urticaria index, IgE FC Receptor antibody functional assay) will be assessed at week 10. Attached to this document is a protocol summary.
Interventions
DRUGNucala
All study participants will receive Nucala (2) 100mg SQ injections administered at two different anatomical sites at week zero, 2,4,6, and 8 for a total of 5 doses.
Sponsors
GlaxoSmithKline
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Mepolizumab for the treatment of chronic spontaneous urticaria
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients 18 years or older. * Clinical and/or histopathological diagnosis of conventional CSU * Unresponsive to oral antihistamine therapy * Good general health as confirmed by medical history * Patients who are willing and capable of cooperating to the extent and degree required by the protocol; and * Patients who read and sign an approved informed consent for this study
Exclusion criteria
* Vulnerable study population * If you are female and pregnant * Biopsy proven neutrophilic rich urticaria * Known history of adverse reaction to mepolizumab (Nucala)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Urticaria Activity Score (UAS7) | Baseline to 10 Weeks | Study participants documented their chronic spontaneous urticaria (CSU) symptoms using a diary, daily scoring for a) the number of wheals \[none (=0 points), \<10 (=1 point), 10-50 (=2 points), or \>50 per day (=3 points)\], and b) the intensity of pruritus \[none (=0 points), mild (=1 point), moderate (=2 points), severe (=3 points)\]. The daily UAS score is summed over a week to calculate the UAS7 score (range: 0-42). Participants were considered responders if they had ≥ 95% reduction in baseline UAS7 score and non-responders if they had \<95% reduction in baseline UAS7 score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Short Form Urticaria Control Test Score (S-UCT) | Baseline to 10 weeks | The short form urticaria control test (S-UCT) is a more recently developed and validated outcome instrument to retrospectively assess urticaria control. The S-UCT consists of 4 questions with each question having 5 answer options scored 0-4 with low points indicating high disease activity and low disease control. The minimum and maximum S-UCT scores are 0-16 with 16 points indicating complete disease control. Participants were considered responders if they had ≥ 95% reduction in baseline S-UCT score and non-responders if they had \<95% reduction in baseline S-UCT score. |
| Change in Long Form Urticaria Control Test (L-UCT) Score | Baseline to 10 Weeks | The long form urticaria control test (L-UCT) is a more recently developed and validated outcome instrument to retrospectively assess urticaria control. The L-UCT consists of 8 questions with each question having 5 answer options scored 0-4 with low points indicating high disease activity and low disease control. The minimum and maximum L-UCT scores are 0-32 with 32 points indicating complete disease control. Participants were considered responders if they had ≥ 95% reduction in baseline L-UCT score and non-responders if they had \<95% reduction in baseline L-UCT score. |
| Change in Itch Severity Score (ISS) | Baseline to 10 weeks | The weekly itch severity score measures the intensity and impact of itching (pruritus). It is calculated using the pruritus score of the daily Urticaria Activity Score (UAS) score summed over a week. Scores range from 0 to 21 with higher scores indicating worse itching. Participants were considered responders if they had ≥ 95% reduction in baseline ISS score and non-responders if they had \<95% reduction in baseline ISS score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm This was an open-label pilot investigation and all study participants were assigned to active treatment. There was no placebo arm in this study.
Nucala: All study participants received Nucala (2) 100mg SQ injections administered at two different anatomical sites at week zero, 2,4,6, and 8 for a total of 5 doses. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Treatment Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 9 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Reduction in Urticaria Activity Score (UAS7)
Study participants documented their chronic spontaneous urticaria (CSU) symptoms using a diary, daily scoring for a) the number of wheals \[none (=0 points), \<10 (=1 point), 10-50 (=2 points), or \>50 per day (=3 points)\], and b) the intensity of pruritus \[none (=0 points), mild (=1 point), moderate (=2 points), severe (=3 points)\]. The daily UAS score is summed over a week to calculate the UAS7 score (range: 0-42). Participants were considered responders if they had ≥ 95% reduction in baseline UAS7 score and non-responders if they had \<95% reduction in baseline UAS7 score.
Time frame: Baseline to 10 Weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm | Reduction in Urticaria Activity Score (UAS7) | Responders | 3 Participants |
| Treatment Arm | Reduction in Urticaria Activity Score (UAS7) | Non-Responders | 7 Participants |
Secondary
Change in Itch Severity Score (ISS)
The weekly itch severity score measures the intensity and impact of itching (pruritus). It is calculated using the pruritus score of the daily Urticaria Activity Score (UAS) score summed over a week. Scores range from 0 to 21 with higher scores indicating worse itching. Participants were considered responders if they had ≥ 95% reduction in baseline ISS score and non-responders if they had \<95% reduction in baseline ISS score.
Time frame: Baseline to 10 weeks
Population: 10 total participants were analyzed. Those 10 participants were further broken down into the following categories non-responders (7) and responders (3), respectively.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Arm | Change in Itch Severity Score (ISS) | Responders | 13 score on a scale |
| Treatment Arm | Change in Itch Severity Score (ISS) | Non-Responders | 1 score on a scale |
Secondary
Change in Long Form Urticaria Control Test (L-UCT) Score
The long form urticaria control test (L-UCT) is a more recently developed and validated outcome instrument to retrospectively assess urticaria control. The L-UCT consists of 8 questions with each question having 5 answer options scored 0-4 with low points indicating high disease activity and low disease control. The minimum and maximum L-UCT scores are 0-32 with 32 points indicating complete disease control. Participants were considered responders if they had ≥ 95% reduction in baseline L-UCT score and non-responders if they had \<95% reduction in baseline L-UCT score.
Time frame: Baseline to 10 Weeks
Population: 10 total participants were analyzed. Those 10 participants were further broken down into the following categories non-responders (7) and responders (3), respectively.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Arm | Change in Long Form Urticaria Control Test (L-UCT) Score | Responders | 21.3 score on a scale |
| Treatment Arm | Change in Long Form Urticaria Control Test (L-UCT) Score | Non-Responders | 1.6 score on a scale |
Secondary
Change in Short Form Urticaria Control Test Score (S-UCT)
The short form urticaria control test (S-UCT) is a more recently developed and validated outcome instrument to retrospectively assess urticaria control. The S-UCT consists of 4 questions with each question having 5 answer options scored 0-4 with low points indicating high disease activity and low disease control. The minimum and maximum S-UCT scores are 0-16 with 16 points indicating complete disease control. Participants were considered responders if they had ≥ 95% reduction in baseline S-UCT score and non-responders if they had \<95% reduction in baseline S-UCT score.
Time frame: Baseline to 10 weeks
Population: 10 total participants were analyzed. Those 10 participants were further broken down into the following categories non-responders (7) and responders (3), respectively.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Arm | Change in Short Form Urticaria Control Test Score (S-UCT) | Responders | 12.3 score on a scale |
| Treatment Arm | Change in Short Form Urticaria Control Test Score (S-UCT) | Non-responders | 0.71 score on a scale |