A 52-week multi-center, randomized, double-blind, placebo controlled, basket study with an open-label extension to investigate the efficacy, safety, and tolerability of remibrutinib (LOU064) in Chronic Inducible Urticaria (CINDU) in adults inadequately controlled by H1-antihistamines

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 Sep 2024 → ongoing

Decision date (initial)

2024-08-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Safety, Efficacy

The purpose of this study is to measure the difference in the proportion of participants achieving complete response with remibrutinib XX mg b.i.d compared with placebo in participants with CINDU (symptomatic dermographism, cold urticaria and cholinergic urticaria) at Week 12.

Secondary objectives 10

1. To demonstrate superiority of remibrutinib versus placebo with regard to change from baseline in ● Total Fric Score (TFS) for symptomatic dermographism cohort at Week 12 ● Critical Temperature Threshold (CTT) for cold urticaria cohort at Week 12 ● Itch response to provocation test for cholinergic urticaria cohort at Week 12
2. To demonstrate superiority of remibrutinib versus placebo on Physician Global assessment (PGA) of severity of hives for cholinergic urticaria cohort at Week 12
3. To demonstrate superiority of remibrutinib versus placebo with regard to ● complete response to provocation test for symptomatic dermographism cohort at Week 24 ● complete response to provocation test for cold urticaria cohort at Week 24 ● complete itch response to provocation test for cholinergic urticaria cohort at Week 24
4. To demonstrate superiority of remibrutinib versus placebo ● in itch NRS following the provocation test for symptomatic dermographism cohort at Week 12. ● in itch NRS following the provocation test for cold urticaria cohort at Week 12
5. To demonstrate superiority of remibrutinib versus placebo with regard to proportion of participants with ● a complete response to FricTest® for symptomatic dermographism cohort at Week 2 ● a complete response to TempTest® for cold urticaria cohort at Week 2 ● a complete itch response to pulse controlled ergometry for cholinergic urticaria cohort at Week 2
6. To demonstrate superiority of remibrutinib versus placebo with regard to ● change from baseline in response to FricTest® for symptomatic dermographism cohort at Week 2 ● change from baseline in response to TempTest® for cold urticaria cohort at Week 2 ● change from baseline in itch following pulse controlled ergometry for cholinergic urticaria at Week 2
7. To demonstrate superiority of remibrutinib versus placebo in itch NRS following the provocation test for ● in itch NRS following the provocation test for symptomatic dermographism cohort at Week 2 ● in itch NRS following the provocation test for for cold urticaria cohort at Week 2 ● Physician Global assessment (PGA) of severity of hives following the provocation test for cholinergic urticaria cohort at Week 2
8. To demonstrate superiority of remibutinib versus placebo in the change in the NRS score for the most bothersome symptom between baseline and week 12 on the Urticaria Symptom Daily Diary (USDD) for symptomatic dermographism, cold urticaria and cholinergic urticaria
9. To demonstrate superiority of remibrutinib versus placebo in achieving DLQI = 0-1 at Week 12 for symptomatic dermographism, cold urticaria and cholinergic urticaria
10. To assess the safety of remibrutinib for symptomatic dermographism, cold urticaria and cholinergic urticaria

Conditions and MedDRA coding

Chronic Inducible Urticaria (CINDU)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male and female participants ≥18 years of age at the time of signing of the ICFs
2. Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for ≥ 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
3. The following response to the provocation test for each subtype is required at the randomization visit : • Symptomatic Dermographism: A Total Fric Score of ≥3 using the FricTest® 4.0 and a numerical rating scale score of ≥5 for itch after the provocation test. • Cold Urticaria: A Critical Threshold Temperature of ≥15°C using the TempTest® 4.0 and a numerical rating scale score of ≥5 for itch after the provocation test. • Cholinergic Urticaria: A physician global assessment of severity of hives ≥ 2 using the Pulse-controlled ergometry test and a numerical rating scale score of ≥5 for itch after the provocation test.
4. Cold Urticaria
5. Cholinergic urticaria: XX

Exclusion criteria 6

1. Previous use of remibrutinib or other BTK inhibitors.
2. Participants who have concomitant CSU at screening. Participants with resolved CSU at the time of screening can be included in the study.
3. Participants who have a familial 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.
4. Participants having a more defined other form of inducible urticaria than the target CINDU that is being considered for the participant's inclusion in this study.
5. Diseases, other than chronic inducible urticaria, with urticaria or angioedema symptoms including but not limited to urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema
6. Any other skin disease associated with chronic itching that might influence, in the investigator’s opinion, the study evaluations and results (e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ● Symptomatic dermographism; Proportion of participants with complete response to Total Fric Score (TFS) following the FricTest® 4.0 at Week 12 ● Cold urticaria: proportion of participants with complete response in Critical Temperature Threshold (CTT) following the TempTest® at Week 12. ● Cholinergic urticaria: proportion of participants with itch NRS=0 following the pulse-controlled ergometry test at Week 12

Secondary endpoints 10

1. ● Symptomatic dermographism: Change from baseline in Total Fric Score (TFS) following the FricTest® at Week 12 ● Cold urticaria: Change from baseline in Critical temperature threshold (CTT) following the TempTest® at Week 12 ● Cholinergic urticaria: Change from baseline in itch NRS following the pulse-controlled ergometry test at Week 12
2. ● Cholinergic urticaria: Proportion of participants with Physician Global Assessment (PGA) of severity of hives = 0 following the pulse-controlled ergometry test at Week 12.
3. ● Symptomatic dermographism: Proportion of participants with complete response to Total Fric Score (TFS) following the FricTest® at Week 24 ● Cold urticaria: Proportion of participants with complete response in Critical temperature Threshold (CTT) following the TempTest® at Week 24 ● Cholinergic urticaria: Proportion of participants with itch NRS=0 following the pulse-controlled ergometry test at Week 24
4. ● Symptomatic dermographism: Change from baseline in itch NRS following the FricTest® at Week 12 ● Cold urticaria: Change from baseline in itch NRS following the TempTest® at Week 12
5. ● Symptomatic dermographism: Proportion of participants with complete response in Total Fric score (TFS) following the FricTest® at Week 2 ● Cold urticaria: Proportion of participants with complete response in Critical temperature threshold (CTT) following the TempTest® at Week 2 ● Cholinergic urticaria: Proportion of participants with itch NRS=0 following the pulse-controlled ergometry test at Week 2
6. ● Symptomatic dermographism: Change from baseline in Total Fric Score (TFS) following the FricTest® at Week 2 ● Cold urticaria: Change from baseline in the Critical Temperature threshold (CTT) following the TempTest® at Week 2 ● Cholinergic urticaria: Change from baseline in itch NRS following the pulse-controlled ergometry test at Week 2
7. ● Symptomatic dermographism: Change from baseline in itch NRS following the FricTest® at Week 2 ● Cold urticaria: Change from baseline in itch NRS following the TempTest® at Week 2 ● Cholinergic urticaria: Proportion of participants with Physician Global assessment (PGA) of severity of hives=0 following the pulse-controlled ergometry test at Week 2
8. ● Change from baseline in the weekly most bothersome symptom NRS score on the USDD at Week 12 for each cohort
9. ● Proportion of participants with DLQI= 0-1 at Week 12 for each cohort
10. ● Safety endpoints for inducible urticaria subtypes 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 Town

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 27

Locations

10 EU/EEA countries · 58 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 159 files

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

Application history

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