A 12-week randomized, participant and investigator blinded, placebo-controlled, exploratory study in adult participants with Chronic Urticaria to assess the efficacy and safety and explore the Mechanism of Action of remibrutinib (LOU064)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

30 Jun 2025 → ongoing

Decision date (initial)

2025-05-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacodynamic

CINDU cohorts: To investigate the efficacy of remibrutinib versus placebo for the most bothersome symptom in CINDU patients
All cohorts: To investigate the impact of remibrutinib versus placebo on urticaria symptom control

Secondary objectives 3

1. All cohorts: To investigate the impact of remibrutinib versus placebo on urticaria symptom control and quality of life
2. CINDU cohorts: To investigate the change in symptoms as collected with USDD in participants treated with remibrutinib versus placebo
3. All cohorts: To investigate the safety of remibrutinib versus placebo in patients with CU

Conditions and MedDRA coding

Chronic Inducible urticaria and Chronic Spontaneous Urticaria

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent must be obtained prior to participation in the study.
2. Male and female participants ≥ 18 years of age at the time of signing of the informed consent forms.
3. CINDU patients: Confirmed diagnosis of CINDU with a duration of ≥ 4 months (defined as onset of CINDU with supporting documentation (e.g. medical record, clinical history, photographs) and inadequate control with H1-AH at local label approved doses at the time of randomization The following response to the provocation test for each CINDU subtype is required before randomization (either during screening or prior to randomization on Day 1): • Symptomatic dermographism: A Total Fric Score of ≥3 using the FricTest® 4.0. • Cold urticaria: A Critical Threshold Temperature of ≥15°C using the TempTest® 4.0. • Cholinergic urticaria: A physician global assessment of severity of hives ≥ 2 using the Pulse-controlled ergometry test after the provocation test. • Heat urticaria: Documented emergence of urticaria symptoms following heat exposure • Solar urticaria: Documented emergence of urticaria symptoms following sunlight exposure and UVA/B or light exposure/phototesting record from source records • Delayed pressure urticaria: symptoms of urticaria as diagnosed by pressure provocation with dermographometer or local application of weight on the lesional skin area (symptoms should be observed 4h to 6h after the trigger) and can be documented by the participant when outpatient. • Aquagenic urticaria: Evidence of urticaria (in patient records) after local exposure to water (e.g. wet blanket or other suitable testing approach). • Contact urticaria: Evidence of urticaria following contact to identified material causing urticaria symptoms.
4. CINDU patients: Patients should be symptomatic for their most bothersome symptom as assessed with the USDD during baseline with a NRS score of 3 or more
5. CSU patients: Diagnosis of CSU (acc. to Zuberbier et al 2022a) not adequately controlled with H1‑AH at approved doses alone for at least 4 weeks prior to randomization, as defined by all of the following: • UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during 7 days prior to randomization • CSU for ≥ 6 months
6. Participants must be willing and able to attend the protocol defined test procedure throughout the study

Exclusion criteria 7

1. Participants who have a familial/hereditary form (e.g. familial cold autoinflammatory syndrome, familial cold urticaria) of the target CINDU that is being considered for the participant's inclusion in this study
2. Diseases, other than CSU or CINDU, with urticaria or angioedema symptoms including but not limited to: • urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), • food allergies yielding urticaria symptoms when the allergen is not avoided by the dietary habits of the participant • hereditary or acquired angioedema.
3. CINDU patients only: To prevent a confounding effect of CSU symptoms, the CINDU study population will consist of participants with predominant CINDU and shoud not have a signficant share of CSU symptoms (that might make the assessment of CINDU symptoms difficult) as per the investigator's judgement.
4. CSU patients only: Patients should have no relevant inducible urticaria trigger
5. Any other skin disease associated with chronic itching that might influence, in the investigator’s opinion, the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism.
6. Known or suspected ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis) and/or known positivity for Human Immunodeficiency Virus (HIV) infection
7. Pretreatment with remibrutinib or another BTK-inhibitor within 4 months prior to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Absolute change from baseline in the weekly most bothersome symptom Numeric Rating Scale (NRS) score on the Urticaria Symptom Daily Diary (USDD) at Week 6
2. Absolute change from baseline in Urticaria Control Test 7 (UCT7) weekly scores at Week 6

Secondary endpoints 4

1. Absolute change from baseline in Urticaria Control test 7 (UCT7) weekly scores at Week 2 and Week 12
2. Dermatology Life Quality Index (DLQI) response defined as DLQI= 0-1 at Week 2, Week 6 and Week 12
3. Absolute change from baseline in USDD weekly component scores at Week 2, Week 6 and Week 12; this includes the change in itch, pain and burning NRS from baseline.
4. Safety endpoints will include but not be limited to: • Occurrence of treatment emergent adverse events (AEs) • Occurrence of treatment emergent serious adverse events (SAEs) • Occurrence of treatment emergent adverse events of special interest (AESIs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 18

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 64 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications