This Was a Dose-finding Study to Evaluate Efficacy and Safety of LOU064 in Patients With CSU Inadequately Controlled by H1-antihistamines

Phase 2

Completed

• Conditions: Chronic Spontaneous Urticaria
• Interventions: Drug: LOU064 Arm 1; Drug: LOU064 Arm 2; Drug: LOU064 Arm 5; Drug: LOU064 Arm 4; Drug: Placebo arm; Drug: LOU064 Arm 3; Drug: LOU064 Arm 6

• Registration Number: NCT03926611
• Lead Sponsor: Novartis Pharmaceuticals

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.

Study Timeline

• Study First Submitted: 2019-04-12
• Study First Submitted QC: 2019-04-23
• Study First Posted: 2019-04-24
• Study Start: 2019-06-06
• Primary Completion: 2021-01-14
• Study Completion: 2021-04-15
• Disposition First Submitted: 2021-07-07
• Disposition First Submitted QC: 2021-07-07
• Disposition First Posted: 2021-07-09
• Results First Submitted: 2022-01-22
• Results First Submitted QC: 2022-01-22
• Results First Posted: 2022-02-16
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-27
• Last Update Posted: 2022-04-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 311

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LOU064 Arm 1	LOU064 Arm 1	10 mg LOU064 qd capsule once daily
LOU064 Arm 2	LOU064 Arm 2	35 mg capsule qd LOU064 once daily
LOU064 Arm 5	LOU064 Arm 5	25 mg capsule LOU064 bid
LOU064 Arm 4	LOU064 Arm 4	10 mg capsule LOU064 bid
Placebo Arm	Placebo arm	Participants took matching placebo twice daily
LOU064 Arm 3	LOU064 Arm 3	100 mg capsule qd LOU064 once daily
LOU064 Arm 6	LOU064 Arm 6	100 mg capsule LOU064 bid

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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)
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).
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 .
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.
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 .
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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Plymouth, United Kingdom