Chronic Spontaneous Urticaria
Conditions
Keywords
BTK inhibitor, Urticaria Activity Score, Angioedema Activity Score, CSU
Brief summary
This was a multicenter, randomized, double-blind and placebo-controlled phase 2b dose-finding study to assess the efficacy and safety of LOU064 in adults chronic spontaneous urticaria (CSU) patients inadequately controlled by H1-antihistamines
Detailed description
This was a global Phase 2b multicenter, randomized, double-blind, parallel-group, placebo-controlled study investigating the efficacy, safety and tolerability of six dosing groups of oral LOU064 in subjects with inadequately controlled CSU despite treatment with (second generation) H1-antihistamine. The study comprised of the 7 treatment arms: LOU064 10 mg q.d., LOU064 35 mg q.d., LOU064 100 mg q.d., LOU064 10 mg b.i.d, LOU064 25 mg b.i.d., LOU064 100 mg b.i.d. and placebo.
Interventions
DRUGLOU064 Arm 1
10 mg LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
DRUGLOU064 Arm 2
35 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
DRUGLOU064 Arm 3
100 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
DRUGLOU064 Arm 4
10mg bid of LOU064 orally, twice daily from Day 1 to 85
DRUGLOU064 Arm 5
25 mg bid of LOU064 orally, twice daily from Day 1 to 85
DRUGLOU064 Arm 6
100 mg bid of LOU064 orally, twice daily from Day 1 to 85
DRUGPlacebo arm
Matching placebo, orally, twice daily from Day 1 to 85
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
This was a global Phase 2b multicenter, randomized, double-blind, parallel-group, placebocontrolled study investigating the efficacy, safety and tolerability of 6 dosing groups of oral LOU064 in subjects with inadequately controlled CSU despite treatment with (second generation) H1-antihistamine. Study duration was 18 weeks (2 weeks of screening period; 12 weeks of treatment period and a 4 weeks follow-up period). Study had 7 arms: 10 mg LOU064 q.d.; 35 mg LOU064 q.d.; 100 mg LOU064 q.d.; 10 mg LOU064 b.i.d.; 25 mg LOU064 b.i.d.; 100 mg LOU064 b.i.d.; and Placebo Throughout study, subjects were treated with a 2nd generation H1-antihistamine at a locally approved licensed posology (background medication). Subjects could take an additional second generation H1-antihistamine that was eliminated primarily via renal excretion (e.g. cetirizine, levocetirizine or bilastine) as rescue medication. Eligible subjects could roll over to extension at Wk 12 or Wk 16
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects aged ≥18 years of age * CSU diagnosis for ≥ 6 months prior to screening * Presence of itch and hives for ≥6 consecutive weeks prior to screening in spite of use of non-sedating H1-antihistamines according to local Treatment guidelines during this time period * UAS7 score (range 0-42) ≥16 and HSS7 score (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1) * Willing and able to complete an Urticaria Participant Daily eDiary (UPDD) for the duration of the study
Exclusion criteria
* Hypersensitivity to any of the study treatments * Clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) * Other diseases with symptoms of urticaria or angioedema * Other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results, * Known or suspected history of an ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (eg tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis), HIV, Hepatitis B/C. * Pregnant or nursing (lactating) women * Women of child-bearing potential not using highly effective methods of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 | Baseline, Week 4 | UAS7 score change (LS mean Change) from baseline at Week 4 estimated with a mixed-effect repeated measurement analysis of UAS7 score change from baseline (FAS) The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (week 4 score minus Baseline score) indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | Week 12 | UAS7=0 and UAS7\<=6 response rate over time by treatment group (non-responder imputation) The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates more severe disease. A negative change score (week 4 score minus Baseline score) indicates improvement. |
| Cumulative Number of Weeks With an AAS7=0 Response | Baseline to Week 12 | The Weekly angioedema activity score (AAS) is a validated tool to assess occurrence of episodes of angioedema. If the subject reports the occurrence of angioedema (opening question) with no, AAS score for this day is 0. If yes is the answer to the opening question, the subject will continue to answer questions about the duration, severity and impact on daily functioning and appearance of the angioedema. The AAS7 is a weekly AAS score (AAS7). Minimum and maximum possible AAS7 scores are 0-105. Higher score means more severe disease. |
| Percentage of Participants With DLQI Score of 0 or 1 | Week 4 and Week 12 | Percentage of subjects with DLQI 0/1 response by treatment group and visit (non-responder imputation) The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL). A DLQI score of 0 or 1 means that there is no impact of a skin disease on the patient's life. |
| Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 | Week 12 | UAS7 score change (LS mean Change) from baseline at Week 12 estimated with a mixed-effect repeated measurement analysis of UAS7 score change from baseline (FAS) |
| Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 4 and Week 12 | Assessment of the area under the blood concentration-time curve (AUC) up to four hours following oral administration at Week 4 and Week 12 . |
| Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 4 and Week 12 | Assessment of the observed maximum blood concentration (Cmax) of LOU064 following drug administration at Week 4 and Week 12 . |
| Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 4 and Week 12 | Assessment of the time to reach the maximum concentration (Tmax) of LOU064 following drug administration at Weeks 4 and 12 |
| Mean Change From Baseline in DLQI Score | Baseline, Week 4 and Week 12 | Summary of DLQI score and change from baseline The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL). |
Countries
Argentina, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Japan, Netherlands, Poland, Russia, Slovakia, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
311 participants enrolled at 82 investigative sites in 17 countries. This Randomized Set included all randomized subjects, regardless of whether or not they actually received study medication. Subjects were analyzed according to the treatment assigned at randomization.
Pre-assignment details
Informed consent was obtained from each subject in writing at screening before any study specific procedure was performed. The study was explained to the subject by the investigator or designee, who answered any questions, and written information was also provided. Re-screening was allowed once and if a subject was re-screened, then the subject had to sign a new informed consent form. .
Participants by arm
| Arm | Count |
|---|---|
| LOU064 Arm 1 10 mg LOU064 qd capsule once daily | 44 |
| LOU064 Arm 2 35 mg capsule qd LOU064 once daily | 44 |
| LOU064 Arm 3 100 mg capsule qd LOU064 once daily | 47 |
| LOU064 Arm 4 10 mg capsule LOU064 bid | 44 |
| LOU064 Arm 5 25 mg capsule LOU064 bid | 44 |
| LOU064 Arm 6 100 mg capsule LOU064 bid | 45 |
| Placebo Arm Participants took matching placebo twice daily | 43 |
| Total | 311 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 3 | 1 | 3 | 0 |
| Overall Study | Covid-19 pandemic | 0 | 0 | 1 | 0 | 1 | 2 | 0 |
| Overall Study | Lack of Efficacy | 1 | 2 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 1 | 1 | 1 | 1 |
| Overall Study | Technical problems | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 0 | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | LOU064 Arm 1 | LOU064 Arm 2 | LOU064 Arm 3 | LOU064 Arm 4 | LOU064 Arm 5 | LOU064 Arm 6 | Placebo Arm | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 5 Participants | 3 Participants | 5 Participants | 5 Participants | 4 Participants | 7 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 39 Participants | 44 Participants | 39 Participants | 39 Participants | 41 Participants | 36 Participants | 279 Participants |
| Age, Continuous | 42.5 Years STANDARD_DEVIATION 16.04 | 44.0 Years STANDARD_DEVIATION 16.47 | 45.2 Years STANDARD_DEVIATION 13.4 | 46.1 Years STANDARD_DEVIATION 15.21 | 47.4 Years STANDARD_DEVIATION 14.62 | 44.9 Years STANDARD_DEVIATION 13.76 | 45.1 Years STANDARD_DEVIATION 15.24 | 45.0 Years STANDARD_DEVIATION 14.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 6 Participants | 7 Participants | 7 Participants | 7 Participants | 9 Participants | 7 Participants | 50 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 36 Participants | 37 Participants | 40 Participants | 36 Participants | 36 Participants | 36 Participants | 35 Participants | 256 Participants |
| Sex: Female, Male Female | 35 Participants | 30 Participants | 39 Participants | 32 Participants | 32 Participants | 29 Participants | 25 Participants | 222 Participants |
| Sex: Female, Male Male | 9 Participants | 14 Participants | 8 Participants | 12 Participants | 12 Participants | 16 Participants | 18 Participants | 89 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 44 | 0 / 47 | 0 / 44 | 0 / 43 | 0 / 45 | 0 / 267 | 0 / 42 |
| other Total, other adverse events | 15 / 44 | 13 / 44 | 10 / 47 | 12 / 44 | 11 / 43 | 13 / 45 | 74 / 267 | 11 / 42 |
| serious Total, serious adverse events | 1 / 44 | 0 / 44 | 0 / 47 | 2 / 44 | 2 / 43 | 0 / 45 | 5 / 267 | 0 / 42 |
Outcome results
Primary
Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4
UAS7 score change (LS mean Change) from baseline at Week 4 estimated with a mixed-effect repeated measurement analysis of UAS7 score change from baseline (FAS) The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (week 4 score minus Baseline score) indicates improvement.
Time frame: Baseline, Week 4
Population: Full Analysis Set (FAS) included all randomized subjects. Following intent-to-treat principle, subjects were analyzed according to the treatment and strata assigned to at randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LOU064 Arm 1 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 | -19.10 Scores on a scale | Standard Error 1.686 |
| LOU064 Arm 2 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 | -19.08 Scores on a scale | Standard Error 1.69 |
| LOU064 Arm 3 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 | -14.65 Scores on a scale | Standard Error 1.624 |
| LOU064 Arm 4 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 | -15.99 Scores on a scale | Standard Error 1.686 |
| LOU064 Arm 5 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 | -20.02 Scores on a scale | Standard Error 1.708 |
| LOU064 Arm 6 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 | -18.06 Scores on a scale | Standard Error 1.691 |
| Placebo Arm | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 | -5.44 Scores on a scale | Standard Error 1.739 |
p-value: <0.000190% CI: [-17.51, -9.81]Mixed Models Analysis
p-value: <0.000190% CI: [-17.49, -9.78]Mixed Models Analysis
p-value: <0.000190% CI: [-12.97, -5.45]Mixed Models Analysis
p-value: <0.000190% CI: [-14.38, -6.72]Mixed Models Analysis
p-value: <0.000190% CI: [-18.43, -10.73]Mixed Models Analysis
p-value: <0.000190% CI: [-16.45, -8.78]Mixed Models Analysis
Secondary
Area Under the Blood Concentration-time Curve (AUC) of LOU064
Assessment of the area under the blood concentration-time curve (AUC) up to four hours following oral administration at Week 4 and Week 12 .
Time frame: Week 4 and Week 12
Population: Full Analysis Set (FAS) included all randomized subjects. Following intent-to-treat principle, subjects were analyzed according to the treatment and strata assigned to at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LOU064 Arm 1 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 4 | 45.2 hr*ng/mL | Standard Deviation 18.4 |
| LOU064 Arm 1 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 12 | 41.8 hr*ng/mL | Standard Deviation 19.5 |
| LOU064 Arm 2 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 4 | 131 hr*ng/mL | Standard Deviation 65.4 |
| LOU064 Arm 2 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 12 | 159 hr*ng/mL | Standard Deviation 151 |
| LOU064 Arm 3 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 4 | 427 hr*ng/mL | Standard Deviation 314 |
| LOU064 Arm 3 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 12 | 441 hr*ng/mL | Standard Deviation 313 |
| LOU064 Arm 4 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 4 | 55.9 hr*ng/mL | Standard Deviation 32.3 |
| LOU064 Arm 4 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 12 | 54.4 hr*ng/mL | Standard Deviation 29.4 |
| LOU064 Arm 5 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 4 | 107 hr*ng/mL | Standard Deviation 56.8 |
| LOU064 Arm 5 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 12 | 118 hr*ng/mL | Standard Deviation 66.6 |
| LOU064 Arm 6 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 4 | 418 hr*ng/mL | Standard Deviation 246 |
| LOU064 Arm 6 | Area Under the Blood Concentration-time Curve (AUC) of LOU064 | Week 12 | 469 hr*ng/mL | Standard Deviation 240 |
Secondary
Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12
UAS7 score change (LS mean Change) from baseline at Week 12 estimated with a mixed-effect repeated measurement analysis of UAS7 score change from baseline (FAS)
Time frame: Week 12
Population: Full Analysis Set (FAS) included all randomized subjects. Following intent-to-treat principle, subjects were analyzed according to the treatment and strata assigned to at randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LOU064 Arm 1 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 | -18.11 Score | Standard Error 1.934 |
| LOU064 Arm 2 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 | -17.97 Score | Standard Error 1.934 |
| LOU064 Arm 3 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 | -15.27 Score | Standard Error 1.85 |
| LOU064 Arm 4 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 | -17.67 Score | Standard Error 1.939 |
| LOU064 Arm 5 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 | -20.21 Score | Standard Error 1.964 |
| LOU064 Arm 6 | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 | -17.38 Score | Standard Error 1.985 |
| Placebo Arm | Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 | -7.87 Score | Standard Error 2.001 |
p-value: <0.000190% CI: [-14.72, -5.77]Mixed Models Analysis
p-value: 0.000190% CI: [-14.58, -5.63]Mixed Models Analysis
p-value: 0.002790% CI: [-11.75, -3.05]Mixed Models Analysis
p-value: 0.000290% CI: [-14.25, -5.35]Mixed Models Analysis
p-value: <0.000190% CI: [-16.82, -7.87]Mixed Models Analysis
p-value: 0.000390% CI: [-14.03, -5.01]Mixed Models Analysis
Secondary
Cumulative Number of Weeks With an AAS7=0 Response
The Weekly angioedema activity score (AAS) is a validated tool to assess occurrence of episodes of angioedema. If the subject reports the occurrence of angioedema (opening question) with no, AAS score for this day is 0. If yes is the answer to the opening question, the subject will continue to answer questions about the duration, severity and impact on daily functioning and appearance of the angioedema. The AAS7 is a weekly AAS score (AAS7). Minimum and maximum possible AAS7 scores are 0-105. Higher score means more severe disease.
Time frame: Baseline to Week 12
Population: Full Analysis Set (FAS) included all randomized subjects. Following intent-to-treat principle, subjects were analyzed according to the treatment and strata assigned to at randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LOU064 Arm 1 | Cumulative Number of Weeks With an AAS7=0 Response | 10.2 Weeks | Standard Deviation 2.33 |
| LOU064 Arm 2 | Cumulative Number of Weeks With an AAS7=0 Response | 10.5 Weeks | Standard Deviation 2.59 |
| LOU064 Arm 3 | Cumulative Number of Weeks With an AAS7=0 Response | 10.0 Weeks | Standard Deviation 3.06 |
| LOU064 Arm 4 | Cumulative Number of Weeks With an AAS7=0 Response | 9.8 Weeks | Standard Deviation 3.05 |
| LOU064 Arm 5 | Cumulative Number of Weeks With an AAS7=0 Response | 10.3 Weeks | Standard Deviation 2.45 |
| LOU064 Arm 6 | Cumulative Number of Weeks With an AAS7=0 Response | 9.2 Weeks | Standard Deviation 3.38 |
| Placebo Arm | Cumulative Number of Weeks With an AAS7=0 Response | 8.2 Weeks | Standard Deviation 3.5 |
Secondary
Mean Change From Baseline in DLQI Score
Summary of DLQI score and change from baseline The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL).
Time frame: Baseline, Week 4 and Week 12
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LOU064 Arm 1 | Mean Change From Baseline in DLQI Score | Week 4 | -9.60 Scores on a scale | Standard Deviation 7.214 |
| LOU064 Arm 1 | Mean Change From Baseline in DLQI Score | Week 12 | -9.03 Scores on a scale | Standard Deviation 6.216 |
| LOU064 Arm 2 | Mean Change From Baseline in DLQI Score | Week 4 | -8.38 Scores on a scale | Standard Deviation 7.241 |
| LOU064 Arm 2 | Mean Change From Baseline in DLQI Score | Week 12 | -7.31 Scores on a scale | Standard Deviation 9.392 |
| LOU064 Arm 3 | Mean Change From Baseline in DLQI Score | Week 4 | -7.18 Scores on a scale | Standard Deviation 7.534 |
| LOU064 Arm 3 | Mean Change From Baseline in DLQI Score | Week 12 | -6.60 Scores on a scale | Standard Deviation 7.798 |
| LOU064 Arm 4 | Mean Change From Baseline in DLQI Score | Week 4 | -6.20 Scores on a scale | Standard Deviation 6.416 |
| LOU064 Arm 4 | Mean Change From Baseline in DLQI Score | Week 12 | -8.25 Scores on a scale | Standard Deviation 6.551 |
| LOU064 Arm 5 | Mean Change From Baseline in DLQI Score | Week 4 | -9.21 Scores on a scale | Standard Deviation 7.994 |
| LOU064 Arm 5 | Mean Change From Baseline in DLQI Score | Week 12 | -8.97 Scores on a scale | Standard Deviation 8.891 |
| LOU064 Arm 6 | Mean Change From Baseline in DLQI Score | Week 4 | -6.15 Scores on a scale | Standard Deviation 5.149 |
| LOU064 Arm 6 | Mean Change From Baseline in DLQI Score | Week 12 | -6.27 Scores on a scale | Standard Deviation 5.513 |
| Placebo Arm | Mean Change From Baseline in DLQI Score | Week 4 | -3.33 Scores on a scale | Standard Deviation 8.09 |
| Placebo Arm | Mean Change From Baseline in DLQI Score | Week 12 | -4.38 Scores on a scale | Standard Deviation 6.78 |
Secondary
Observed Maximum Blood Concentration (Cmax) of LOU064
Assessment of the observed maximum blood concentration (Cmax) of LOU064 following drug administration at Week 4 and Week 12 .
Time frame: Week 4 and Week 12
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LOU064 Arm 1 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 4 | 27.6 ng/mL | Standard Deviation 13.7 |
| LOU064 Arm 1 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 12 | 26.1 ng/mL | Standard Deviation 14.5 |
| LOU064 Arm 2 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 4 | 67.2 ng/mL | Standard Deviation 32.7 |
| LOU064 Arm 2 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 12 | 80.3 ng/mL | Standard Deviation 53.9 |
| LOU064 Arm 3 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 4 | 194 ng/mL | Standard Deviation 142 |
| LOU064 Arm 3 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 12 | 199 ng/mL | Standard Deviation 137 |
| LOU064 Arm 4 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 4 | 32.2 ng/mL | Standard Deviation 18.7 |
| LOU064 Arm 4 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 12 | 31.2 ng/mL | Standard Deviation 16 |
| LOU064 Arm 5 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 4 | 55.5 ng/mL | Standard Deviation 34.7 |
| LOU064 Arm 5 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 12 | 64.9 ng/mL | Standard Deviation 42.3 |
| LOU064 Arm 6 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 4 | 196 ng/mL | Standard Deviation 144 |
| LOU064 Arm 6 | Observed Maximum Blood Concentration (Cmax) of LOU064 | Week 12 | 219 ng/mL | Standard Deviation 125 |
Secondary
Percentage of Participants With DLQI Score of 0 or 1
Percentage of subjects with DLQI 0/1 response by treatment group and visit (non-responder imputation) The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL). A DLQI score of 0 or 1 means that there is no impact of a skin disease on the patient's life.
Time frame: Week 4 and Week 12
Population: Full Analysis Set (FAS) included all randomized subjects. Following intent-to-treat principle, subjects were analyzed according to the treatment and strata assigned to at randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LOU064 Arm 1 | Percentage of Participants With DLQI Score of 0 or 1 | Week 4 | 38.6 Percentage of participants |
| LOU064 Arm 1 | Percentage of Participants With DLQI Score of 0 or 1 | Week 12 | 34.1 Percentage of participants |
| LOU064 Arm 2 | Percentage of Participants With DLQI Score of 0 or 1 | Week 4 | 29.5 Percentage of participants |
| LOU064 Arm 2 | Percentage of Participants With DLQI Score of 0 or 1 | Week 12 | 40.9 Percentage of participants |
| LOU064 Arm 3 | Percentage of Participants With DLQI Score of 0 or 1 | Week 4 | 29.8 Percentage of participants |
| LOU064 Arm 3 | Percentage of Participants With DLQI Score of 0 or 1 | Week 12 | 38.3 Percentage of participants |
| LOU064 Arm 4 | Percentage of Participants With DLQI Score of 0 or 1 | Week 4 | 29.5 Percentage of participants |
| LOU064 Arm 4 | Percentage of Participants With DLQI Score of 0 or 1 | Week 12 | 40.9 Percentage of participants |
| LOU064 Arm 5 | Percentage of Participants With DLQI Score of 0 or 1 | Week 4 | 51.2 Percentage of participants |
| LOU064 Arm 5 | Percentage of Participants With DLQI Score of 0 or 1 | Week 12 | 53.5 Percentage of participants |
| LOU064 Arm 6 | Percentage of Participants With DLQI Score of 0 or 1 | Week 4 | 33.3 Percentage of participants |
| LOU064 Arm 6 | Percentage of Participants With DLQI Score of 0 or 1 | Week 12 | 35.6 Percentage of participants |
| Placebo Arm | Percentage of Participants With DLQI Score of 0 or 1 | Week 4 | 16.7 Percentage of participants |
| Placebo Arm | Percentage of Participants With DLQI Score of 0 or 1 | Week 12 | 28.6 Percentage of participants |
Secondary
Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6)
UAS7=0 and UAS7\<=6 response rate over time by treatment group (non-responder imputation) The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates more severe disease. A negative change score (week 4 score minus Baseline score) indicates improvement.
Time frame: Week 12
Population: Full Analysis Set (FAS) included all randomized subjects. Following intent-to-treat principle, subjects were analyzed according to the treatment and strata assigned to at randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LOU064 Arm 1 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS7=0 | 29.5 Percent of participants |
| LOU064 Arm 1 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS<=6 | 47.7 Percent of participants |
| LOU064 Arm 2 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS7=0 | 29.5 Percent of participants |
| LOU064 Arm 2 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS<=6 | 52.3 Percent of participants |
| LOU064 Arm 3 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS7=0 | 29.8 Percent of participants |
| LOU064 Arm 3 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS<=6 | 38.3 Percent of participants |
| LOU064 Arm 4 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS7=0 | 31.8 Percent of participants |
| LOU064 Arm 4 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS<=6 | 47.7 Percent of participants |
| LOU064 Arm 5 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS7=0 | 41.9 Percent of participants |
| LOU064 Arm 5 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS<=6 | 55.8 Percent of participants |
| LOU064 Arm 6 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS7=0 | 26.7 Percent of participants |
| LOU064 Arm 6 | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS<=6 | 42.2 Percent of participants |
| Placebo Arm | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS7=0 | 14.3 Percent of participants |
| Placebo Arm | Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) | UAS<=6 | 28.6 Percent of participants |
Secondary
Time to Reach the Maximum Concentration (Tmax) of LOU064
Assessment of the time to reach the maximum concentration (Tmax) of LOU064 following drug administration at Weeks 4 and 12
Time frame: Week 4 and Week 12
Population: Full Analysis Set (FAS) included all randomized subjects. Following intent-to-treat principle, subjects were analyzed according to the treatment and strata assigned to at randomization.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LOU064 Arm 1 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 12 | 1.17 hours |
| LOU064 Arm 1 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 4 | 1.33 hours |
| LOU064 Arm 2 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 12 | 1.48 hours |
| LOU064 Arm 2 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 4 | 1.54 hours |
| LOU064 Arm 3 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 12 | 1.61 hours |
| LOU064 Arm 3 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 4 | 1.52 hours |
| LOU064 Arm 4 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 12 | 1.17 hours |
| LOU064 Arm 4 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 4 | 0.900 hours |
| LOU064 Arm 5 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 4 | 1.15 hours |
| LOU064 Arm 5 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 12 | 1.32 hours |
| LOU064 Arm 6 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 4 | 1.52 hours |
| LOU064 Arm 6 | Time to Reach the Maximum Concentration (Tmax) of LOU064 | Week 12 | 1.39 hours |