52 weeks double-blind, double-dummy, randomized placebo-controlled trial to evaluate safety, efficacy and tolerability of remibrutinib in comparison to placebo with omalizumab as active control in adult patients with CSU and inadequate response to H1-antihistamine and an open-label 52-week optional extension to assess long-term efficacy, safety and tolerability of remibrutinib 25 mg b.i.d.

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] - Skin and Connective Tissue Diseases [C17]

Trial duration

12 Mar 2024 → ongoing

Decision date (initial)

2024-02-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-502161-19-00

ClinicalTrials.gov

NCT06042478

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Pharmacogenetic, Others, Therapy

To demonstrate that remibrutinib (25 mg b.i.d.) is superior to placebo in CSU participants with respect to change from baseline in UAS7, ISS7 and HSS7 at Week 12.

Secondary objectives 5

1. To demonstrate that remibrutinib (25 mg b.i.d.) is superior to placebo in CSU participants with respect to the proportion of participants achieving complete absence of hives and itch (UAS7 = 0) at Week 12.
2. To demonstrate that remibrutinib (25 mg b.i.d.) is superior to placebo in CSU participants with respect to change from baseline in ISS7 score at Week 12
3. To demonstrate that remibrutinib (25 mg b.i.d.) is superior to placebo in CSU participants with respect to change from baseline in HSS7 score at Week 12
4. To demonstrate that remibrutinib (25 mg b.i.d.) is superior to placebo in CSU participants with respect to change from baseline in UAS7 score at Week 12
5. To demonstrate the safety and tolerability of remibrutinib (25 mg b.i.d.)

Conditions and MedDRA coding

Chronic Spontaneous Urticaria

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male and female adult participants ≥18 years of age at the time of signing the informed consent.
2. CSU duration for ≥ 6 months prior to screening.
3. Diagnosis of CSU inadequately controlled by second generation H1-AH at the time of randomization, defined as: • The presence of itch and hives for ≥6 consecutive weeks prior to screening, despite the use of second-generation H1-AH during this time period. • UAS7 score (range 0-42) ≥16, ISS7 score (range 0-21) ≥ 6 and HSS7 score (range 0- 21) ≥ 6 during the 7 days prior to randomization (Day 1).
4. Documentation of hives within three months before randomization.
5. Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol.
6. Participants must not have had more than one missing UPDD entry (either morning or evening) in the 7 days prior to randomization (Day 1).

Exclusion criteria 8

1. Prior exposure to ligelizumab, omalizumab and other biologics with any effect in CSU, including anti-IgE therapies.
2. Significant bleeding risk or coagulation disorders.
3. History of gastrointestinal bleeding.
4. Requirement for anti-platelet or anti-coagulant medication.
5. History or current hepatic disease.
6. Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant.
7. Evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines.
8. Documented history of anaphylaxis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change from baseline in UAS7, ISS7 and HSS7 at Week 12

Secondary endpoints 5

1. Achievement of UAS7=0 (yes/no) at Week 12
2. Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score at Week 12
3. Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score at Week 12
4. Absolute change from baseline in UAS7 at Week 12
5. Occurrence of treatment-emergent adverse events and serious adverse events (SAEs) during the study

Investigational products

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

Test 1

Comparator 1

Placebo 3

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 26

Locations

10 EU/EEA countries · 60 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 223 files

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

Application history

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