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

A Multicenter, Randomized, Double-blind, Placebo- Controlled Phase 2b Dose-finding Study to Investigate the Efficacy, Safety and Tolerability of LOU064 in Adult Chronic Spontaneous Urticaria (CSU) Patients Inadequately Controlled by H1-antihistamines

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

Study Overview

• Status: Completed
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: LOU064 Arm 1; Drug: LOU064 Arm 2; Drug: LOU064 Arm 3; Drug: LOU064 Arm 4; Drug: LOU064 Arm 5; Drug: LOU064 Arm 6; Drug: Placebo arm

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 Type: Interventional
• Enrollment (Actual): 311
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, 1035
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1414AIF
      • Novartis Investigative Site
    • La Plata, Buenos Aires, Argentina, B1902COS
      • Novartis Investigative Site
  • Mendoza
    • Ciudad de Mendoza, Mendoza, Argentina, M5500AWD
      • Novartis Investigative Site
• Belgium
  • Liege, Belgium, 4000
    • Novartis Investigative Site
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1V 4W2
    • Novartis Investigative Site
  • Alberta
    • Edmonton, Alberta, Canada, T5K 1X3
      • Novartis Investigative Site
  • Ontario
    • London, Ontario, Canada, N6H 5L5
      • Novartis Investigative Site
    • Niagara Falls, Ontario, Canada, L2H 1H5
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1G 6C6
      • Novartis Investigative Site
  • Quebec
    • Verdun, Quebec, Canada, H4G 3E7
      • Novartis Investigative Site
• Czechia
  • Tabor, Czechia, 390 01
    • Novartis Investigative Site
  • Czech Republic
    • Prague 8, Czech Republic, Czechia, 180 00
      • Novartis Investigative Site
  • Prague 1
    • Prague, Prague 1, Czechia, 11000
      • Novartis Investigative Site
• Denmark
  • Arhus C, Denmark, DK 8000
    • Novartis Investigative Site
  • Copenhagen NV, Denmark, 2400
    • Novartis Investigative Site
• France
  • Lille Cedex, France, 59037
    • Novartis Investigative Site
  • Nantes Cedex 1, France, 44093
    • Novartis Investigative Site
  • Nice Cedex, France, 06202
    • Novartis Investigative Site
  • Pierre Benite Cedex, France, 69495
    • Novartis Investigative Site
  • Rouen, France, 76031
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Gera, Germany, 07548
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Muenchen, Germany, 80377
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1085
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Oroshaza, Hungary, 5900
    • Novartis Investigative Site
  • Pecs, Hungary, 7623
    • Novartis Investigative Site
  • Szolnok, Hungary, 5000
    • Novartis Investigative Site
  • Hajdu Bihar
    • Debrecen, Hajdu Bihar, Hungary, 4026
      • Novartis Investigative Site
• Japan
  • Aichi
    • Ichinomiya, Aichi, Japan, 491-0041
      • Novartis Investigative Site
  • Chiba
    • Funabashi, Chiba, Japan
      • Novartis Investigative Site
  • Hiroshima
    • Hiroshima City, Hiroshima, Japan, 734-8551
      • Novartis Investigative Site
  • Hokkaido
    • Obihiro, Hokkaido, Japan, 080 0013
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 220-6208
      • Novartis Investigative Site
    • Yokohama, Kanagawa, Japan, 221-0825
      • Novartis Investigative Site
    • Yokohama, Kanagawa, Japan, 240-0013
      • Novartis Investigative Site
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Novartis Investigative Site
    • Koto, Tokyo, Japan, 136-0074
      • Novartis Investigative Site
  • Toyama
    • Takaoka, Toyama, Japan, 933-0871
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
  • Utrecht, Netherlands, 3584CX
    • Novartis Investigative Site
• Poland
  • Gdansk, Poland, 80 803
    • Novartis Investigative Site
  • Lodz, Poland, 90-265
    • Novartis Investigative Site
  • Lodz, Poland, 90-436
    • Novartis Investigative Site
  • Rzeszow, Poland, 35 055
    • Novartis Investigative Site
  • Warszawa, Poland, 02 777
    • Novartis Investigative Site
  • Wroclaw, Poland, 50-566
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 123182
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 194325
    • Novartis Investigative Site
  • St.-Petersburg, Russian Federation, 195112
    • Novartis Investigative Site
  • Stavropol, Russian Federation, 355000
    • Novartis Investigative Site
• Slovakia
  • Nove Zamky, Slovakia, 940 34
    • Novartis Investigative Site
  • Svidnik, Slovakia, 08901
    • Novartis Investigative Site
  • Slovak Republic
    • Kosice, Slovak Republic, Slovakia, 040 15
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03010
      • Novartis Investigative Site
• Turkey
  • Denizli, Turkey, 20070
    • Novartis Investigative Site
  • Talas / Kayseri, Turkey, 38039
    • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Novartis Investigative Site
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Novartis Investigative Site
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • Oxford, United Kingdom, OX3 7LJ
    • Novartis Investigative Site
  • Plymouth, United Kingdom, PL6 8DH
    • Novartis Investigative Site
• United States
  • Arizona
    • Litchfield Park, Arizona, United States, 85340
      • Novartis Investigative Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Novartis Investigative Site
  • California
    • Mission Viejo, California, United States, 92691
      • Novartis Investigative Site
    • San Diego, California, United States, 92123
      • Novartis Investigative Site
    • Walnut Creek, California, United States, 94598
      • Novartis Investigative Site
    • Westminster, California, United States, 92683
      • Novartis Investigative Site
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • Novartis Investigative Site
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Novartis Investigative Site
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Novartis Investigative Site
  • Ohio
    • Grove City, Ohio, United States, 43123
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LOU064 Arm 1; 10 mg LOU064 qd capsule once daily	Drug: LOU064 Arm 1; 10 mg LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
Experimental: LOU064 Arm 2; 35 mg capsule qd LOU064 once daily	Drug: LOU064 Arm 2; 35 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
Experimental: LOU064 Arm 3; 100 mg capsule qd LOU064 once daily	Drug: LOU064 Arm 3; 100 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
Experimental: LOU064 Arm 4; 10 mg capsule LOU064 bid	Drug: LOU064 Arm 4; 10mg bid of LOU064 orally, twice daily from Day 1 to 85
Experimental: LOU064 Arm 5; 25 mg capsule LOU064 bid	Drug: LOU064 Arm 5; 25 mg bid of LOU064 orally, twice daily from Day 1 to 85
Experimental: LOU064 Arm 6; 100 mg capsule LOU064 bid	Drug: LOU064 Arm 6; 100 mg bid of LOU064 orally, twice daily from Day 1 to 85
Placebo Comparator: Placebo Arm; Participants took matching placebo twice daily	Drug: Placebo arm; Matching placebo, orally, twice daily from Day 1 to 85

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Week 12
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.	Week 12
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.	Baseline to Week 12
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.	Week 4 and Week 12
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).	Baseline, Week 4 and Week 12
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 .	Week 4 and Week 12
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 .	Week 4 and Week 12
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	Week 4 and Week 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2019
• Primary Completion (Actual): January 14, 2021
• Study Completion (Actual): April 15, 2021

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: BTK inhibitor; Urticaria Activity Score; CSU; Angioedema Activity Score
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Chronic Urticaria
• Other Study ID Numbers: CLOU064A2201; 2018-000993-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No