Trial Outcomes & Findings for A Study of LY3454738 in Adults With Chronic Spontaneous Urticaria (NCT NCT04159701)

Last Updated: 2022-03-11

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2022-03-11

Participant Flow

Participant milestones

Participant milestones
Measure	Sequence Group 1: (500 mg LY3454738, Placebo) Participants received 500 milligram (mg) LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks. Participants did not receive study drug during the follow-up period.	Sequence Group 2: (Placebo, 500 mg LY3454738) Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks. Participants did not receive study drug during the follow-up period.
Period 1: Treatment Period STARTED	39	13
Period 1: Treatment Period Received at Least One Dose of Study Drug	39	13
Period 1: Treatment Period COMPLETED	31	12
Period 1: Treatment Period NOT COMPLETED	8	1
Washout Period STARTED	31	12
Washout Period COMPLETED	18	8
Washout Period NOT COMPLETED	13	4
Period 2: Treatment Period (Crossover) STARTED	18	8
Period 2: Treatment Period (Crossover) COMPLETED	18	5
Period 2: Treatment Period (Crossover) NOT COMPLETED	0	3
Post-treatment Follow-up STARTED	29	9
Post-treatment Follow-up COMPLETED	19	6
Post-treatment Follow-up NOT COMPLETED	10	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence Group 1: (500 mg LY3454738, Placebo) Participants received 500 milligram (mg) LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks. Participants did not receive study drug during the follow-up period.	Sequence Group 2: (Placebo, 500 mg LY3454738) Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks. Participants did not receive study drug during the follow-up period.
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
Washout Period site terminated by sponsor	0	1
Washout Period study terminated by sponsor	10	3
Washout Period Withdrawal by Subject	1	0
Washout Period Inadvertent Enrollment	1	0
Washout Period Miscellaneous	1	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 Study Terminated by Sponsor	6	3
Post-treatment Follow-up Withdrawal by Subject	3	0
Post-treatment Follow-up Inadvertent Enrollment	1	0

Baseline Characteristics

A Study of LY3454738 in Adults With Chronic Spontaneous Urticaria

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence Group 1: (500 mg LY3454738, Placebo) n=39 Participants Participants received 500 mg LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks.	Sequence Group 2: (Placebo, 500 mg LY3454738) n=13 Participants Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks.	Total n=52 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	38 Participants n=5 Participants	13 Participants n=7 Participants	51 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	11 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants	13 Participants n=7 Participants	46 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	33 Participants n=5 Participants	10 Participants n=7 Participants	43 Participants n=5 Participants
Region of Enrollment Poland	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Germany	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Urticaria Activity Score Over 7 Days (UAS7) Score	26.51 units on a scale STANDARD_DEVIATION 7.48 • n=5 Participants	24.26 units on a scale STANDARD_DEVIATION 5.23 • n=7 Participants	25.95 units on a scale STANDARD_DEVIATION 7.00 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Sequence Group 1: (500 mg LY3454738, Placebo) n=39 Participants Participants received 500 mg LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks.	Sequence Group 2: (Placebo, 500 mg LY3454738) n=13 Participants Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks.
Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7)	-6.38 units on a scale Standard Error 1.645	-9.32 units on a scale Standard Error 2.864

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug.

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).

Outcome measures

Outcome measures
Measure	Sequence Group 1: (500 mg LY3454738, Placebo) n=39 Participants Participants received 500 mg LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks.	Sequence Group 2: (Placebo, 500 mg LY3454738) n=13 Participants Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks.
Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7)	-2.91 units on a scale Standard Error 0.780	-4.21 units on a scale Standard Error 1.367

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug.

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).

Outcome measures

Outcome measures
Measure	Sequence Group 1: (500 mg LY3454738, Placebo) n=39 Participants Participants received 500 mg LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks.	Sequence Group 2: (Placebo, 500 mg LY3454738) n=13 Participants Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks.
Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7)	-3.45 units on a scale Standard Error 0.931	-5.17 units on a scale Standard Error 1.631

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who received at least one dose of study drug and had UAS7 ≤6.

Outcome measures

Outcome measures
Measure	Sequence Group 1: (500 mg LY3454738, Placebo) n=39 Participants Participants received 500 mg LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks.	Sequence Group 2: (Placebo, 500 mg LY3454738) n=13 Participants Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks.
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	23.1 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who received at least one dose of study drug and had UAS7 ≤6.

Outcome measures

Outcome measures
Measure	Sequence Group 1: (500 mg LY3454738, Placebo) n=39 Participants Participants received 500 mg LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks.	Sequence Group 2: (Placebo, 500 mg LY3454738) n=13 Participants Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks.
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	23.1 percentage of participants

SECONDARY outcome

Timeframe: 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.

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 336 Hours (AUC \[0-336h\]) of LY3454738

Outcome measures

Outcome measures
Measure	Sequence Group 1: (500 mg LY3454738, Placebo) n=44 Participants Participants received 500 mg LY3454738 intravenously (IV) every 2 weeks (Q2W) for 12 weeks followed by placebo for 12 weeks.	Sequence Group 2: (Placebo, 500 mg LY3454738) Participants received Placebo for 12 weeks followed by 500 mg LY3454738 IV Q2W for 12 weeks.
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 336 Hours (AUC [0-336h]) of LY3454738	53400 microgramshour per milliliter( ugh/mL) Geometric Coefficient of Variation 49	—

SECONDARY outcome

Population: All randomized participants who received at least one dose of LY3454738 and had evaluable PK data.

PK: Maximum Concentration (Cmax) of LY3454738