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NCT04109313

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

Completed Phase 2 Results posted Last updated 20 June 2024
What this trial tests

Phase 2 trial testing LOU064 in Chronic Spontaneous Urticaria in 229 participants. Completed in 9 September 2022.

Timeline
24 October 2019
Primary endpoint
9 September 2022
9 September 2022

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment229
Start date24 October 2019
Primary completion9 September 2022
Estimated completion9 September 2022
Sites69 locations across Denmark, France, Japan, Russia, Slovakia, Belgium, United Kingdom, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 99, any sex, with Chronic Spontaneous Urticaria. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-emergent Adverse Events (AEs) Primary · From first dose of treatment up to 28 days after last dose, assessed up to 56 weeks

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

AEs
GroupValue95% CI
Treated Cohort139
Deaths
GroupValue95% CI
Treated Cohort0
Non-fatal Serious AEs (SAEs)
GroupValue95% CI
Treated Cohort6
SAE(s)
GroupValue95% CI
Treated Cohort6
Discontinued treatment due to any AE(s)
GroupValue95% CI
Treated Cohort11
Discontinued treatment due to any SAE(s)
GroupValue95% CI
Treated Cohort2
Treatment interruption due to AE(s)
GroupValue95% CI
Treated Cohort13
Treatment interruption due to SAE(s)
GroupValue95% CI
Treated Cohort1
Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 of the Treatment Period Secondary · Baseline, Week 4 of 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 neede

GroupValue95% CI
Treated Cohort-17.58± 13.400
Percentage of Participants With Well-controlled Disease (UAS7≤6) at Week 4 of the Treatment Period Secondary · 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 need

GroupValue95% CI
Treated Cohort51.044.9 – 57.1
Percentage of Participants With Complete Response (UAS7=0) at Week 4 of the Treatment Period Secondary · 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 need

GroupValue95% CI
Treated Cohort27.322.2 – 33.1
Percentage of Participants With Well-controlled Disease (UAS7≤ 6) Overtime Secondary · From baseline until Week 52 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 need

Baseline
GroupValue95% CI
Treated Cohort1.00.2 – 3.5
Week 1
GroupValue95% CI
Treated Cohort37.431.4 – 43.8
Week 4
GroupValue95% CI
Treated Cohort52.746.4 – 58.8
Week 12
GroupValue95% CI
Treated Cohort56.650.1 – 63.0
Week 20
GroupValue95% CI
Treated Cohort62.756.1 – 68.9
Week 28
GroupValue95% CI
Treated Cohort68.561.9 – 74.5
Week 40
GroupValue95% CI
Treated Cohort66.559.6 – 72.7
Week 52
GroupValue95% CI
Treated Cohort68.061.1 – 74.3
Change From Baseline in UAS7 Overtime Secondary · From baseline until Week 52 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 need

Week 1
GroupValue95% CI
Treated Cohort-14.76± 11.502
Week 4
GroupValue95% CI
Treated Cohort-17.58± 13.400
Week 12
GroupValue95% CI
Treated Cohort-19.37± 12.502
Week 20
GroupValue95% CI
Treated Cohort-20.61± 11.634
Week 28
GroupValue95% CI
Treated Cohort-21.54± 11.525
Week 40
GroupValue95% CI
Treated Cohort-21.25± 11.400
Week 52
GroupValue95% CI
Treated Cohort-21.82± 10.699

Adverse events — posted to ClinicalTrials.gov

Time frame: In the Treated cohort, treatment-emergent AEs were collected from first dose of treatment up to 28 days post last dose, up to 56 weeks; and deaths were collected from first dose of treatment until end of study, assessed up to 68 weeks. In the Treatment-free cohort, AEs and deaths were collected from start of observation period until relapse (UAS7≥16) or end of observation period, up to 12 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment-free Cohort (Observational Period)
Serious: 1/68 (1%)
Deaths: 0/68
Treated Cohort (Treatment+Follow-up Period)
Serious: 6/194 (3%)
Deaths: 0/194

Serious adverse events (7 terms)

ReactionSystemTreatment-free Cohort (Obs…Treated Cohort (Treatment+…
COVID-19 pneumoniaInfections and infestations
MelaenaGastrointestinal disorders
Chest painGeneral disorders
AppendicitisInfections and infestations
Tibia fractureInjury, poisoning and procedural complications
Ovarian cystReproductive system and breast disorders
Superficial spreading melanoma stage unspecifiedNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (4 terms — click to expand)

ReactionSystemTreatment-free Cohort (Obs…Treated Cohort (Treatment+…
Chronic spontaneous urticariaSkin and subcutaneous tissue disorders
COVID-19Infections and infestations
HeadacheNervous system disorders
EczemaSkin and subcutaneous tissue disorders

Most-reported serious reactions: COVID-19 pneumonia, Melaena, Chest pain, Appendicitis, Tibia fracture, Ovarian cyst, Superficial spreading melanoma stage unspecified.

Data from ClinicalTrials.gov NCT04109313 adverse events section.

Sponsor's own description

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)

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Small Molecule NF-κB Pathway Inhibitors in Clinic.
    Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
  2. Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions.
    Mendes-Bastos P, Brasileiro A, Kolkhir P, Frischbutter S, et al · · 2022 · cited 67× · PMID 35175630 · DOI 10.1111/all.15261
  3. Recent Advances in BTK Inhibitors for the Treatment of Inflammatory and Autoimmune Diseases.
    Zhang D, Gong H, Meng F. · · 2021 · cited 45× · PMID 34443496 · DOI 10.3390/molecules26164907
  4. Bruton's tyrosine kinase inhibition for the treatment of allergic disorders.
    Lin EV, Suresh RV, Dispenza MC. · · 2024 · cited 20× · PMID 38492772 · DOI 10.1016/j.anai.2024.03.002
  5. Update on the Treatment of Chronic Spontaneous Urticaria.
    Kolkhir P, Fok JS, Kocatürk E, Li PH, et al · · 2025 · cited 10× · PMID 40074986 · DOI 10.1007/s40265-025-02170-4
  6. Biologicals in Treatment of Chronic Urticaria: A Narrative Review.
    Mustari AP, Bishnoi A, Kumaran MS. · · 2023 · cited 7× · PMID 36776192 · DOI 10.4103/idoj.idoj_145_22
  7. Monoclonal Antibodies in Treating Chronic Spontaneous Urticaria: New Drugs for an Old Disease.
    Manti S, Giallongo A, Papale M, Parisi GF, et al · · 2022 · cited 7× · PMID 35956071 · DOI 10.3390/jcm11154453
  8. Selected Poster Abstracts from MauiDerm 2023 for Dermatologists
    · 2023

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