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

NCT04109313 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CLOU064A2201E12019-001074-29
• Study Type: interventional
• Target: 229
• Locations: 15 countries
• Sites: 69

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)

Conditions

Chronic Spontaneous Urticaria

Keywords

Chronic spontaneous urticaria; BTK Inhibitor; Long term safety; Urticaria activity score

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 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

  Week 4 of the treatment period

• Percentage of Participants With Complete Response (UAS7=0) at Week 4 of the Treatment Period

  Week 4 of the treatment period

• Percentage of Participants With Well-controlled Disease (UAS7≤ 6) Overtime

  From baseline until Week 52 of the treatment period

• Change From Baseline in UAS7 Overtime

  From baseline until Week 52 of the treatment period

Study Arms (1)

All participants

EXPERIMENTAL

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

Interventions

LOU064 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.

All participants

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Participants transitioning at Week 12 of CLOU064A2201 with a UAS7 score of ≥16 will be allocated to the treatment period.
• Participants transitioning at Week 16 of CLOU064A2201 with a UAS7 score of ≥16 will be allocated to the treatment period.
• Participants transitioning at Week 16 of CLOU064A2201 with a UAS7 score of \<16 will be allocated to the observational period.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (69)

Novartis Investigative Site

Litchfield Park, Arizona, 85340, United States

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Little Rock, Arkansas, 72205, United States

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Mission Viejo, California, 92691, United States

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San Diego, California, 92123, United States

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Walnut Creek, California, 94598, United States

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Pembroke Pines, Florida, 33028, United States

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Owensboro, Kentucky, 42301, United States

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Ypsilanti, Michigan, 48197, United States

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St Louis, Missouri, 63141, United States

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Grove City, Ohio, 43123, United States

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CABA, Buenos Aires, C1414AIF, Argentina

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Novartis Investigative Site

La Plata, Buenos Aires, B1902COS, Argentina

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Mendoza, Mendoza Province, M5500AWD, Argentina

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Novartis Investigative Site

CABA, 1035, Argentina

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Edegem, Antwerpen, 2650, Belgium

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Liège, 4000, Belgium

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Novartis Investigative Site

Edmonton, Alberta, T5K 1X3, Canada

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London, Ontario, N6H 5L5, Canada

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Niagara Falls, Ontario, L2H 1H5, Canada

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Ottawa, Ontario, K1G 6C6, Canada

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Québec, Quebec, G1V 4W2, Canada

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Verdun, Quebec, H4G 3E7, Canada

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Novartis Investigative Site

Prague, Czech Republic, 180 00, Czechia

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Novartis Investigative Site

Prague, Prague 1, 11000, Czechia

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Novartis Investigative Site

Tábor, 390 01, Czechia

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Novartis Investigative Site

Arhus C, DK 8000, Denmark

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Novartis Investigative Site

Copenhagen NV, 2400, Denmark

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Novartis Investigative Site

Lille, 59037, France

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Nantes, 44093, France

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Novartis Investigative Site

Nice, 06202, France

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Novartis Investigative Site

Orosháza, Bekes County, 5900, Hungary

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Novartis Investigative Site

Budapest, 1085, Hungary

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Novartis Investigative Site

Debrecen, 4032, Hungary

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Pécs, 7632, Hungary

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Szolnok, 5000, Hungary

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Novartis Investigative Site

Ichinomiya, Aichi-ken, 491-0041, Japan

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Funabashi, Chiba, 273-0031, Japan

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Novartis Investigative Site

Hiroshima, Hiroshima, 734-8551, Japan

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Novartis Investigative Site

Obihiro, Hokkaido, 080 0013, Japan

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Novartis Investigative Site

Yokohama, Kanagawa, 220-6208, Japan

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Novartis Investigative Site

Yokohama, Kanagawa, 221-0825, Japan

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Novartis Investigative Site

Yokohama, Kanagawa, 240-0013, Japan

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Novartis Investigative Site

Itabashi-ku, Tokyo, 173-8610, Japan

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Novartis Investigative Site

Takaoka, Toyama, 933-0871, Japan

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Novartis Investigative Site

Gdansk, 80 803, Poland

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Novartis Investigative Site

Lodz, 90-265, Poland

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Novartis Investigative Site

Lodz, 90-436, Poland

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Novartis Investigative Site

Rzeszów, 35 055, Poland

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Novartis Investigative Site

Warsaw, 02 777, Poland

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Novartis Investigative Site

Moscow, 123182, Russia

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Novartis Investigative Site

Saint Petersburg, 194354, Russia

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Novartis Investigative Site

Saint Petersburg, 195112, Russia

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Novartis Investigative Site

Stavropol, 355000, Russia

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Novartis Investigative Site

Košice, Slovak Republic, 040 15, Slovakia

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Novartis Investigative Site

Nové Zámky, 940 34, Slovakia

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Novartis Investigative Site

Svidník, 08901, Slovakia

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Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

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Novartis Investigative Site

Alicante, Valencia, 03010, Spain

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Novartis Investigative Site

Madrid, 28006, Spain

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Novartis Investigative Site

Madrid, 28046, Spain

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Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

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Novartis Investigative Site

Denizli, 20070, Turkey (Türkiye)

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Novartis Investigative Site

Talas / Kayseri, 38039, Turkey (Türkiye)

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Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

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Novartis Investigative Site

London, SE1 9RT, United Kingdom

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Novartis Investigative Site

Oxford, OX3 7LJ, United Kingdom

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Novartis Investigative Site

Plymouth, PL6 8DH, United Kingdom

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Related Publications (1)

• 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.

  PMID: 37866460 DERIVED

Related Links

• Patient Lay Trial Summary

MeSH Terms

Conditions

Chronic Urticaria

Interventions

remibrutinib

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceutical

  Novartis Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: September 30, 2019
• Study Start: October 24, 2019
• Primary Completion: September 9, 2022
• Study Completion: September 9, 2022
• Last Updated: June 20, 2024
• Results First Posted: September 29, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

FR (3); CZ (3); BE (2); TU (3); SL (3); ES (6); HU (5); DK (2); CA (6); AR (4); JP (9); GB (4); RU (4); US (10); PL (5)