An Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of LOU064 in Subjects With CSU

An Open-label, Multicenter, Extension Study to Evaluate the Long-term Safety and Tolerability of LOU064 in Eligible Subjects With CSU Who Have Participated in CLOU064A2201

The main objective to assess the long-term safety and tolerability of LOU064 in patients with chronic spontaneous urticaria (CSU) who have participated in study CLOU064A2201 (NCT03926611)

Study Overview

• Status: Completed
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: LOU064

Detailed Description

This was an open-label, single-arm, multicenter, long-term safety and tolerability extension study for CSU patients rolling over from study CLOU064A2201 (NCT03926611).

Subjects rolling over from CLOU064A2201 with a weekly Urticaria Activity Score (UAS7)<16 after the follow-up period at Week 16 were further followed up without receiving LOU064 for up to 12 weeks (observational period). If there was a relapse (UAS7≥16 at least once), the 12-week observational period was terminated, and subjects entered the treatment period. Subjects who never relapsed within 12 weeks completed the study after the observational period without treatment.

Subjects who rolled over from CLOU064A2201 with a UAS7≥16 at Week 12 or Week 16, as well as those subjects who relapsed during the 12-week observational period, were treated with 100 mg LOU064 twice a day (b.i.d.) open-label for 52 weeks. No background medication with a second-generation H1-antihistamine was permitted up to Week 4 of the treatment period. Subjects who completed the treatment period or who discontinued treatment early were followed-up for a minimum duration of 4 weeks. Subjects who had a UAS7≤6 at Week 52 of the treatment period had their follow-up period extended until relapse (UAS7≥16) for up to a total of 16 weeks.

• Study Type: Interventional
• Enrollment (Actual): 229
• 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
• Hungary
  • Budapest, Hungary, 1085
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Pecs, Hungary, 7632
    • Novartis Investigative Site
  • Szolnok, Hungary, 5000
    • Novartis Investigative Site
  • Bekes
    • Oroshaza, Bekes, Hungary, 5900
      • Novartis Investigative Site
• Japan
  • Aichi
    • Ichinomiya, Aichi, Japan, 491-0041
      • Novartis Investigative Site
  • Chiba
    • Funabashi, Chiba, Japan, 273-0031
      • 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
  • Toyama
    • Takaoka, Toyama, Japan, 933-0871
      • 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
• Russian Federation
  • Moscow, Russian Federation, 123182
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 194354
    • 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
  • 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: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participants must provide written informed consent prior to any assessments.
• Participants must be willing and able to complete a daily symptom eDiary throughout the study and adhere to the study visit schedules.

• Participants transitioning from the CLOU064A2201 trial must have completed either the Week 12 visit (end of treatment period) or the Week 16 visit (end of follow-up period). They will be assigned to either the treatment period or the observational period based on their UAS7 score (average score from the 7 days prior to the respective visit) as follows:

  1. Participants transitioning at Week 12 of CLOU064A2201 with a UAS7 score of ≥16 will be allocated to the treatment period.
  2. Participants transitioning at Week 16 of CLOU064A2201 with a UAS7 score of ≥16 will be allocated to the treatment period.
  3. Participants transitioning at Week 16 of CLOU064A2201 with a UAS7 score of <16 will be allocated to the observational period.

Key Exclusion Criteria:

• Participants with a clearly defined predominant or sole trigger for their chronic urticaria, such as chronic inducible urticaria (including symptomatic dermographism, cold-induced, heat-induced, solar-induced, pressure-induced, delayed pressure-induced, aquagenic-induced, cholinergic-induced, or contact-induced urticaria).
• Participants with other diseases presenting with urticaria or angioedema symptoms, including but not limited to urticaria vasculitis, urticarial pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, or acquired/drug-induced urticaria.
• Participants with any other skin disease associated with chronic itching that, in the opinion of the investigator, could affect the study evaluations and results, such as atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or psoriasis.
• Participants with a history or current diagnosis of ECG abnormalities that indicate a significant safety risk for their participation in the study, including:
• Concomitant clinically significant cardiac arrhythmias (e.g., sustained ventricular tachycardia) and clinically significant second or third-degree AV block without a pacemaker.
• History of familiar long QT syndrome or a known family history of Torsades de Pointes.
• Resting heart rate (as determined by physical exam or 12-lead ECG) below 50 bpm.
• Resting QTcF interval ≥450 msec (in males) or ≥460 msec (in females) at day 1 of the treatment period or inability to determine the QTcF interval.
• Use of agents known to prolong the QT interval, unless they can be permanently discontinued for the duration of the study.
• Participants with a significant risk of bleeding or coagulation disorders.
• Participants with a known or suspected history of an ongoing, chronic, or recurrent infectious disease, including but not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis, or aspergillosis), HIV, or Hepatitis B/C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All participants; Participants with UAS7<16 at Week 16 of CLOU064A2201 were followed up to 12 weeks without receiving treatment (observational period). If participants relapsed (UAS7≥16 at least once), they were transitioned to the treatment period. Otherwise, they were discontinued from the study. Participants with a UAS7≥16 at Week 12 or Week 16 in the CLOU064A2201, as well as participants who experienced a relapse during the 12-week observational period, were administered 100 mg of LOU064 b.i.d. open-label for up to 52 weeks.

Drug: LOU064; Participants with a UAS7≥16 at Week 12 or Week 16 in the CLOU064A2201, as well as participants who experienced a relapse during the 12-week observational period, were administered LOU064 50mg capsules b.i.d. (i.e. two capsules of LOU064 50mg in the morning and two capsules of LOU064 50mg in the evening) from Day 1 up to Week 52 of the Treatment period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (AEs)	An AE refers to any undesirable medical occurrence, such as an unintended sign (including abnormal laboratory findings), symptom, or disease, experienced by a participant. Serious AEs (SAEs) is defined as any AE that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or any other medically significant condition. Treatment-emergent AEs were defined as AEs that either begin on the same day or after the first dose of study medication during the treatment period in the extension study or worsen on the same day or after the first dose of study medication in the extension study and within the minimum of either 28 days post last dose or the end of the study visit. The number of participants with treatment-emergent AEs was summarized.	From first dose of treatment up to 28 days after last dose, assessed up to 56 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 of the Treatment Period	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. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. The change from baseline in UAS7 at Week 4 of the treatment period was calculated. A negative change score from baseline indicates improvement. The UAS7 at baseline was considered as the UAS7 derived over the last 7 days before day 1 of the treatment period.	Baseline, Week 4 of treatment period
Percentage of Participants With Well-controlled Disease (UAS7≤6) at Week 4 of the Treatment Period	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. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. Missing values were imputed by non-responder imputation method regardless of the reason for missingness. The percentage of subjects with UAS7≤ 6 at Week 4 of the treatment period was calculated. The 90% confidence interval was derived based on the score method with continuity correction.	Week 4 of the treatment period
Percentage of Participants With Complete Response (UAS7=0) at Week 4 of the Treatment Period	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. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. Missing values were imputed by non-responder imputation method regardless of the reason for missingness. The percentage of subjects with UAS7= 0 at Week 4 of the treatment period was calculated. The 90% confidence interval was derived based on the score method with continuity correction.	Week 4 of the treatment period
Percentage of Participants With Well-controlled Disease (UAS7≤ 6) Overtime	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. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. The percentage of subjects with UAS7≤ 6 during the treatment period was calculated. The 90% confidence interval was derived based on the score method with continuity correction. The UAS7 at baseline was considered as the UAS7 derived over the last 7 days before day 1 of the treatment period.	From baseline until Week 52 of the treatment period
Change From Baseline in UAS7 Overtime	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. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. The change from baseline in UAS7 during the treatment period was calculated. A negative change score from baseline indicates improvement. The UAS7 at baseline was considered as the UAS7 derived over the last 7 days before day 1 of the treatment period.	From baseline until Week 52 of the treatment period

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceutical, Novartis Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2019
• Primary Completion (Actual): September 9, 2022
• Study Completion (Actual): September 9, 2022

Study Registration Dates

• First Submitted: September 27, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: BTK Inhibitor; Chronic spontaneous urticaria; Long term safety; Urticaria activity score
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Disease Attributes; Skin Diseases, Vascular; Hypersensitivity; Chronic Disease; Urticaria; Chronic Urticaria
• Other Study ID Numbers: CLOU064A2201E1; 2019-001074-29 (EudraCT Number)

Plan for Individual participant data (IPD)

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

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect 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