Chronic Spontaneous Urticaria
Conditions
Brief summary
The reason for this study is to see if the study drug LY3454738 is safe and effective as treatment for participants with hives that are caused by chronic spontaneous urticaria (CSU) and that are not controlled with H1-antihistamines.
Interventions
DRUGLY3454738
Administered IV
DRUGPlacebo
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Must agree to use appropriate birth control throughout the study * Must have a diagnosis of CSU for at least 6 months * Must have CSU symptoms for at least 8 consecutive weeks despite taking anti-histamines * Must agree to take an anti-histamine every day during the trial * Must be willing to enter information about symptoms in an electronic diary twice a day
Exclusion criteria
* Must not have a cause, other than CSU, for itching, hives, and/or angioedema (swelling beneath the skin) * Must not have a current or recent active infection requiring antibiotics * Must not have a history of anaphylaxis (severe, life threatening allergic reaction) * Must not have asthma requiring medications other than short acting beta agonists (albuterol, etc.) * Must not have received prior treatment with omalizumab, ligelizumab, or other experimental biologic for CSU
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) | Baseline, Week 12 | The UAS7 is the sum of the daily urticaria activity scores (UAS) over a 7-day period and ranges from 0 to 42. The daily UAS is the sum of the daily itch severity score (ISS) and daily number of hives score, and ranges from 0 to 6. The baseline UAS7 is the sum of the daily UAS over the 7 days prior to the first treatment. A higher UAS or higher UAS7 indicates greater urticaria disease activity.The ANCOVA model includes treatment as a factor and baseline UAS7 score in First 12-Week treatment period as covariates. Missing Week 12 scores will be imputed by carrying forward the participants' baseline scores (BOCF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) | Baseline, Week 12 | The HSS7 is the sum of the daily number of hives over a 7-day period and ranges from 0 to 21. The daily number of hives score (also called HSS) is the average of the morning and evening number of hive scores on a four-point scale of 0 (none), 1 (between 1 and 6 hives, inclusive), 2 (between 7 and 12 hives, inclusive), and 3 (greater than 12 hives). The baseline weekly HSS7 is the sum of the HSS over the 7 days prior to the first treatment. A higher HSS or higher HSS7 indicates a greater number of hives. The ANCOVA model includes treatment as a factor and baseline UAS7 score in First 12-Week treatment period as covariates. Missing Week 12 scores will be imputed by carrying forward the participants' baseline scores (BOCF). |
| Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< 28 vs >= 28) Score) | Week 12 | The UAS7 is the sum of the daily urticaria activity scores (UAS) over a 7-day period and ranges from 0 to 42. The daily UAS is the sum of the daily itch severity score (ISS) and daily number of hives score, and ranges from 0 to 6. The baseline UAS7 is the sum of the daily UAS over the 7 days prior to the first treatment. A higher UAS or higher UAS7 indicates greater urticaria disease activity. |
| Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) | Baseline, Week 12 | The ISS7 is the sum of the daily ISS over a 7-day period and ranges from 0 to 21. The daily ISS is the average of the morning and evening ISS on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The baseline ISS7 is the sum of the daily ISS over the 7 days prior to the first treatment. A higher ISS or higher ISS7 indicates more severe itching. The ANCOVA model includes treatment as a factor and baseline UAS7 score in First 12-Week treatment period as covariates. Missing Week 12 scores will be imputed by carrying forward the participants' baseline scores (BOCF). |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 336 Hours (AUC [0-336h]) of LY3454738 | Before Infusion, after infusion, 1 hour after infusion and 2 hours after infusion on Day 1; Before Infusion on Day 8, 15, 29, 43, 57, 71, 85, 92, 99, 113, 127, 141, 155, 169 and Post-Treatment Follow-up | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 336 Hours (AUC \[0-336h\]) of LY3454738 |
| PK: Maximum Concentration (Cmax) of LY3454738 | Before Infusion, after infusion, 1 hour after infusion and 2 hours after infusion on Day 1; Before Infusion on Day 8, 15, 29, 43, 57, 71, 85, 92, 99, 113, 127, 141, 155, 169 and Post-Treatment Follow-up | PK: Maximum Concentration (Cmax) of LY3454738 |
| Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< Median vs >= Median) Score) | Week 12 | The UAS7 is the sum of the daily urticaria activity scores (UAS) over a 7-day period and ranges from 0 to 42.The daily UAS is the sum of the daily itch severity score (ISS) and daily number of hives score, and ranges from 0 to 6. The baseline UAS7 is the sum of the daily UAS over the 7 days prior to the first treatment. A higher UAS or higher UAS7 indicates greater urticaria disease activity. |
Countries
Germany, Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence Group 1: (500 mg LY3454738, Placebo) Participants received 500 mg LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks. | 39 |
| Sequence Group 2: (Placebo, 500 mg LY3454738) Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks. | 13 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1: Treatment Period | Pregnancy | 1 | 0 |
| Period 1: Treatment Period | Study Terminated by sponsor | 4 | 1 |
| Period 1: Treatment Period | Withdrawal by Subject | 3 | 0 |
| Period 2: Treatment Period (Crossover) | Study Terminated by Sponsor | 0 | 2 |
| Period 2: Treatment Period (Crossover) | Withdrawal by Subject | 0 | 1 |
| Post-treatment Follow-up | Inadvertent Enrollment | 1 | 0 |
| Post-treatment Follow-up | Study Terminated by Sponsor | 6 | 3 |
| Post-treatment Follow-up | Withdrawal by Subject | 3 | 0 |
| Washout Period | Inadvertent Enrollment | 1 | 0 |
| Washout Period | Miscellaneous | 1 | 0 |
| Washout Period | site terminated by sponsor | 0 | 1 |
| Washout Period | study terminated by sponsor | 10 | 3 |
| Washout Period | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sequence Group 1: (500 mg LY3454738, Placebo) | Sequence Group 2: (Placebo, 500 mg LY3454738) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 13 Participants | 51 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 13 Participants | 46 Participants |
| Region of Enrollment Germany | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Poland | 5 Participants | 1 Participants | 6 Participants |
| Region of Enrollment United States | 33 Participants | 10 Participants | 43 Participants |
| Sex: Female, Male Female | 30 Participants | 11 Participants | 41 Participants |
| Sex: Female, Male Male | 9 Participants | 2 Participants | 11 Participants |
| Urticaria Activity Score Over 7 Days (UAS7) Score | 26.51 units on a scale STANDARD_DEVIATION 7.48 | 24.26 units on a scale STANDARD_DEVIATION 5.23 | 25.95 units on a scale STANDARD_DEVIATION 7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 13 | 0 / 8 | 0 / 18 | 0 / 38 |
| other Total, other adverse events | 4 / 39 | 4 / 13 | 1 / 8 | 7 / 18 | 2 / 38 |
| serious Total, serious adverse events | 0 / 39 | 0 / 13 | 0 / 8 | 0 / 18 | 0 / 38 |
Outcome results
Primary
Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7)
The UAS7 is the sum of the daily urticaria activity scores (UAS) over a 7-day period and ranges from 0 to 42. The daily UAS is the sum of the daily itch severity score (ISS) and daily number of hives score, and ranges from 0 to 6. The baseline UAS7 is the sum of the daily UAS over the 7 days prior to the first treatment. A higher UAS or higher UAS7 indicates greater urticaria disease activity.The ANCOVA model includes treatment as a factor and baseline UAS7 score in First 12-Week treatment period as covariates. Missing Week 12 scores will be imputed by carrying forward the participants' baseline scores (BOCF).
Time frame: Baseline, Week 12
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sequence Group 1: (500 mg LY3454738, Placebo) | Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) | -6.38 units on a scale | Standard Error 1.645 |
| Sequence Group 2: (Placebo, 500 mg LY3454738) | Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) | -9.32 units on a scale | Standard Error 2.864 |
p-value: 0.3895% CI: [-3.73, 9.6]Mixed Models Analysis
Secondary
Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7)
The HSS7 is the sum of the daily number of hives over a 7-day period and ranges from 0 to 21. The daily number of hives score (also called HSS) is the average of the morning and evening number of hive scores on a four-point scale of 0 (none), 1 (between 1 and 6 hives, inclusive), 2 (between 7 and 12 hives, inclusive), and 3 (greater than 12 hives). The baseline weekly HSS7 is the sum of the HSS over the 7 days prior to the first treatment. A higher HSS or higher HSS7 indicates a greater number of hives. The ANCOVA model includes treatment as a factor and baseline UAS7 score in First 12-Week treatment period as covariates. Missing Week 12 scores will be imputed by carrying forward the participants' baseline scores (BOCF).
Time frame: Baseline, Week 12
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sequence Group 1: (500 mg LY3454738, Placebo) | Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) | -3.45 units on a scale | Standard Error 0.931 |
| Sequence Group 2: (Placebo, 500 mg LY3454738) | Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) | -5.17 units on a scale | Standard Error 1.631 |
p-value: 0.36995% CI: [-2.09, 5.53]Mixed Models Analysis
Secondary
Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7)
The ISS7 is the sum of the daily ISS over a 7-day period and ranges from 0 to 21. The daily ISS is the average of the morning and evening ISS on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The baseline ISS7 is the sum of the daily ISS over the 7 days prior to the first treatment. A higher ISS or higher ISS7 indicates more severe itching. The ANCOVA model includes treatment as a factor and baseline UAS7 score in First 12-Week treatment period as covariates. Missing Week 12 scores will be imputed by carrying forward the participants' baseline scores (BOCF).
Time frame: Baseline, Week 12
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sequence Group 1: (500 mg LY3454738, Placebo) | Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) | -2.91 units on a scale | Standard Error 0.78 |
| Sequence Group 2: (Placebo, 500 mg LY3454738) | Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) | -4.21 units on a scale | Standard Error 1.367 |
p-value: 0.41595% CI: [-1.89, 4.5]Mixed Models Analysis
Secondary
Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< 28 vs >= 28) Score)
The UAS7 is the sum of the daily urticaria activity scores (UAS) over a 7-day period and ranges from 0 to 42. The daily UAS is the sum of the daily itch severity score (ISS) and daily number of hives score, and ranges from 0 to 6. The baseline UAS7 is the sum of the daily UAS over the 7 days prior to the first treatment. A higher UAS or higher UAS7 indicates greater urticaria disease activity.
Time frame: Week 12
Population: All randomized participants who received at least one dose of study drug and had UAS7 ≤6.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence Group 1: (500 mg LY3454738, Placebo) | Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< 28 vs >= 28) Score) | 15.4 percentage of participants |
| Sequence Group 2: (Placebo, 500 mg LY3454738) | Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< 28 vs >= 28) Score) | 23.1 percentage of participants |
p-value: 0.67495% CI: [0.14, 2.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< Median vs >= Median) Score)
The UAS7 is the sum of the daily urticaria activity scores (UAS) over a 7-day period and ranges from 0 to 42.The daily UAS is the sum of the daily itch severity score (ISS) and daily number of hives score, and ranges from 0 to 6. The baseline UAS7 is the sum of the daily UAS over the 7 days prior to the first treatment. A higher UAS or higher UAS7 indicates greater urticaria disease activity.
Time frame: Week 12
Population: All randomized participants who received at least one dose of study drug and had UAS7 ≤6.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence Group 1: (500 mg LY3454738, Placebo) | Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< Median vs >= Median) Score) | 15.4 percentage of participants |
| Sequence Group 2: (Placebo, 500 mg LY3454738) | Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< Median vs >= Median) Score) | 23.1 percentage of participants |
p-value: 0.67495% CI: [0.13, 2.68]Cochran-Mantel-Haenszel
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 336 Hours (AUC [0-336h]) of LY3454738
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 336 Hours (AUC \[0-336h\]) of LY3454738
Time frame: Before Infusion, after infusion, 1 hour after infusion and 2 hours after infusion on Day 1; Before Infusion on Day 8, 15, 29, 43, 57, 71, 85, 92, 99, 113, 127, 141, 155, 169 and Post-Treatment Follow-up
Population: All randomized participants who received at least one dose of LY3454738 and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sequence Group 1: (500 mg LY3454738, Placebo) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 336 Hours (AUC [0-336h]) of LY3454738 | 53400 micrograms*hour per milliliter( ug*h/mL) | Geometric Coefficient of Variation 49 |
Secondary
PK: Maximum Concentration (Cmax) of LY3454738
PK: Maximum Concentration (Cmax) of LY3454738
Time frame: Before Infusion, after infusion, 1 hour after infusion and 2 hours after infusion on Day 1; Before Infusion on Day 8, 15, 29, 43, 57, 71, 85, 92, 99, 113, 127, 141, 155, 169 and Post-Treatment Follow-up
Population: All randomized participants who received at least one dose of LY3454738 and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sequence Group 1: (500 mg LY3454738, Placebo) | PK: Maximum Concentration (Cmax) of LY3454738 | 256 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 30.8 |