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

NCT ID: NCT04109313

Last Updated: 2024-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 229 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-24
• Study Completion Date: 2022-09-09

Brief Summary

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)

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.

Conditions

Chronic Spontaneous Urticaria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

LOU064

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceutical

Role: STUDY_DIRECTOR

Novartis Pharmaceutical

Locations

Novartis Investigative Site

Litchfield Park, Arizona, United States

Novartis Investigative Site

Little Rock, Arkansas, United States

Novartis Investigative Site

Mission Viejo, California, United States

Novartis Investigative Site

San Diego, California, United States

Novartis Investigative Site

Walnut Creek, California, United States

Novartis Investigative Site

Pembroke Pines, Florida, United States

Novartis Investigative Site

Owensboro, Kentucky, United States

Novartis Investigative Site

Ypsilanti, Michigan, United States

Novartis Investigative Site

St Louis, Missouri, United States

Novartis Investigative Site

Grove City, Ohio, United States

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

La Plata, Buenos Aires, Argentina

Novartis Investigative Site

Mendoza, Mendoza Province, Argentina

Novartis Investigative Site

CABA, , Argentina

Novartis Investigative Site

Edegem, Antwerpen, Belgium

Novartis Investigative Site

Liège, , Belgium

Novartis Investigative Site

Edmonton, Alberta, Canada

Novartis Investigative Site

London, Ontario, Canada

Novartis Investigative Site

Niagara Falls, Ontario, Canada

Novartis Investigative Site

Ottawa, Ontario, Canada

Novartis Investigative Site

Québec, Quebec, Canada

Novartis Investigative Site

Verdun, Quebec, Canada

Novartis Investigative Site

Prague, Czech Republic, Czechia

Novartis Investigative Site

Prague, Prague 1, Czechia

Novartis Investigative Site

Tábor, , Czechia

Novartis Investigative Site

Arhus C, , Denmark

Novartis Investigative Site

Copenhagen NV, , Denmark

Novartis Investigative Site

Lille, , France

Novartis Investigative Site

Nantes, , France

Novartis Investigative Site

Nice, , France

Novartis Investigative Site

Orosháza, Bekes County, Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Debrecen, , Hungary

Novartis Investigative Site

Pécs, , Hungary

Novartis Investigative Site

Szolnok, , Hungary

Novartis Investigative Site

Ichinomiya, Aichi-ken, Japan

Novartis Investigative Site

Funabashi, Chiba, Japan

Novartis Investigative Site

Hiroshima, Hiroshima, Japan

Novartis Investigative Site

Obihiro, Hokkaido, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Itabashi-ku, Tokyo, Japan

Novartis Investigative Site

Takaoka, Toyama, Japan

Novartis Investigative Site

Gdansk, , Poland

Novartis Investigative Site

Lodz, , Poland

Novartis Investigative Site

Lodz, , Poland

Novartis Investigative Site

Rzeszów, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Stavropol, , Russia

Novartis Investigative Site

Košice, Slovak Republic, Slovakia

Novartis Investigative Site

Nové Zámky, , Slovakia

Novartis Investigative Site

Svidník, , Slovakia

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Alicante, Valencia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Istanbul, TUR, Turkey (Türkiye)

Novartis Investigative Site

Denizli, , Turkey (Türkiye)

Novartis Investigative Site

Talas / Kayseri, , Turkey (Türkiye)

Novartis Investigative Site

Leeds, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Oxford, , United Kingdom

Novartis Investigative Site

Plymouth, , United Kingdom

Countries

United States; Argentina; Belgium; Canada; Czechia; Denmark; France; Hungary; Japan; Poland; Russia; Slovakia; Spain; Turkey (Türkiye); United Kingdom

References

Jain V, Gimenez-Arnau A, Hayama K, Reich A, Carr W, Tillinghast J, Dahale S, Lheritier K, Walsh P, Zharkov A, Hugot S, Haemmerle S. Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. J Allergy Clin Immunol. 2024 Feb;153(2):479-486.e4. doi: 10.1016/j.jaci.2023.10.007. Epub 2023 Oct 20.

Reference Type: DERIVED

PMID: 37866460 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1569

Patient Lay Trial Summary

Other Identifiers

2019-001074-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLOU064A2201E1

Identifier Type: -

Identifier Source: org_study_id