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

NCT03926611 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLOU064A22012018-000993-31
• Study Type: interventional
• Target: 311
• Locations: 17 countries
• Sites: 82

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

Conditions

Chronic Spontaneous Urticaria

Keywords

BTK inhibitor; Urticaria Activity Score; Angioedema Activity Score; CSU

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12

  Week 12

• Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6)

  Week 12

• Cumulative Number of Weeks With an AAS7=0 Response

  Baseline to Week 12

• Percentage of Participants With DLQI Score of 0 or 1

  Week 4 and Week 12

• Mean Change From Baseline in DLQI Score

  Baseline, Week 4 and Week 12

Study Arms (7)

LOU064 Arm 1

EXPERIMENTAL

10 mg LOU064 qd capsule once daily

Drug: LOU064 Arm 1

LOU064 Arm 2

EXPERIMENTAL

35 mg capsule qd LOU064 once daily

Drug: LOU064 Arm 2

LOU064 Arm 3

EXPERIMENTAL

100 mg capsule qd LOU064 once daily

Drug: LOU064 Arm 3

LOU064 Arm 4

EXPERIMENTAL

10 mg capsule LOU064 bid

Drug: LOU064 Arm 4

LOU064 Arm 5

EXPERIMENTAL

25 mg capsule LOU064 bid

Drug: LOU064 Arm 5

LOU064 Arm 6

EXPERIMENTAL

100 mg capsule LOU064 bid

Drug: LOU064 Arm 6

Placebo Arm

PLACEBO COMPARATOR

Participants took matching placebo twice daily

Drug: Placebo arm

Interventions

LOU064 Arm 1 DRUG

10 mg LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85

LOU064 Arm 1

LOU064 Arm 2 DRUG

35 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85

LOU064 Arm 2

LOU064 Arm 3 DRUG

100 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85

LOU064 Arm 3

LOU064 Arm 4 DRUG

10mg bid of LOU064 orally, twice daily from Day 1 to 85

LOU064 Arm 4

LOU064 Arm 5 DRUG

25 mg bid of LOU064 orally, twice daily from Day 1 to 85

LOU064 Arm 5

LOU064 Arm 6 DRUG

100 mg bid of LOU064 orally, twice daily from Day 1 to 85

LOU064 Arm 6

Placebo arm DRUG

Matching placebo, orally, twice daily from Day 1 to 85

Placebo Arm

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (82)

Novartis Investigative Site

Litchfield Park, Arizona, 85340, United States

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Novartis Investigative Site

Little Rock, Arkansas, 72205, United States

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Novartis Investigative Site

Mission Viejo, California, 92691, United States

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Novartis Investigative Site

San Diego, California, 92123, United States

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Novartis Investigative Site

Walnut Creek, California, 94598, United States

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Novartis Investigative Site

Westminster, California, 92683, United States

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Novartis Investigative Site

Pembroke Pines, Florida, 33028, United States

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Novartis Investigative Site

Owensboro, Kentucky, 42301, United States

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Novartis Investigative Site

Ypsilanti, Michigan, 48197, United States

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Novartis Investigative Site

St Louis, Missouri, 63141, United States

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Novartis Investigative Site

Grove City, Ohio, 43123, United States

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Novartis Investigative Site

CABA, Buenos Aires, C1414AIF, Argentina

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Novartis Investigative Site

La Plata, Buenos Aires, B1902COS, Argentina

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Novartis Investigative Site

Mendoza, Mendoza Province, M5500AWD, Argentina

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Novartis Investigative Site

CABA, 1035, Argentina

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Novartis Investigative Site

Edegem, Antwerpen, 2650, Belgium

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Novartis Investigative Site

Liège, 4000, Belgium

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Novartis Investigative Site

Edmonton, Alberta, T5K 1X3, Canada

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Novartis Investigative Site

London, Ontario, N6H 5L5, Canada

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Novartis Investigative Site

Niagara Falls, Ontario, L2H 1H5, Canada

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Ottawa, Ontario, K1G 6C6, Canada

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Novartis Investigative Site

Verdun, Quebec, H4G 3E7, Canada

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Novartis Investigative Site

Québec, G1V 4W2, 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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Novartis Investigative Site

Nantes, 44093, France

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Novartis Investigative Site

Nice, 06202, France

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Novartis Investigative Site

Pierre-Bénite, 69495, France

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Novartis Investigative Site

Rouen, 76031, France

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Dresden, 01307, Germany

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Novartis Investigative Site

Gera, 07548, Germany

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Novartis Investigative Site

Hanover, 30625, Germany

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Novartis Investigative Site

München, 80377, Germany

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Novartis Investigative Site

Debrecen, Hajdú-Bihar, 4026, 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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Novartis Investigative Site

Orosháza, 5900, Hungary

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Novartis Investigative Site

Pécs, 7623, Hungary

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Novartis Investigative Site

Szolnok, 5000, Hungary

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Novartis Investigative Site

Ichinomiya, Aichi-ken, 491-0041, Japan

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Novartis Investigative Site

Funabashi, Chiba, 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

Koto, Tokyo, 136-0074, Japan

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Novartis Investigative Site

Takaoka, Toyama, 933-0871, Japan

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Novartis Investigative Site

Amsterdam, 1105 AZ, Netherlands

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Novartis Investigative Site

Utrecht, 3584CX, Netherlands

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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

Wroclaw, 50-566, Poland

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Novartis Investigative Site

Moscow, 123182, Russia

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Novartis Investigative Site

Saint Petersburg, 194325, 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 Links

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

MeSH Terms

Conditions

Chronic Urticaria

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

(862) 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was a global Phase 2b multicenter, randomized, double-blind, parallel-group, placebocontrolled study investigating the efficacy, safety and tolerability of 6 dosing groups of oral LOU064 in subjects with inadequately controlled CSU despite treatment with (second generation) H1-antihistamine. Study duration was 18 weeks (2 weeks of screening period; 12 weeks of treatment period and a 4 weeks follow-up period). Study had 7 arms: 10 mg LOU064 q.d.; 35 mg LOU064 q.d.; 100 mg LOU064 q.d.; 10 mg LOU064 b.i.d.; 25 mg LOU064 b.i.d.; 100 mg LOU064 b.i.d.; and Placebo Throughout study, subjects were treated with a 2nd generation H1-antihistamine at a locally approved licensed posology ("background medication"). Subjects could take an additional second generation H1-antihistamine that was eliminated primarily via renal excretion (e.g. cetirizine, levocetirizine or bilastine) as rescue medication. Eligible subjects could roll over to extension at Wk 12 or Wk 16

Study Record Dates

• First Submitted: April 12, 2019
• First Posted: April 24, 2019
• Study Start: June 6, 2019
• Primary Completion: January 14, 2021
• Study Completion: April 15, 2021
• Last Updated: April 29, 2022
• Results First Posted: February 16, 2022

Record last verified: 2022-04

Locations

CZ (3); RU (4); CA (6); ES (6); DE (5); PL (6); NL (2); JP (10); SL (3); TU (3); DK (2); GB (4); HU (6); US (11); AR (4); FR (5); BE (2)