An Extension Study of Long-term Efficacy, Safety and Tolerability of Remibrutinib in Chronic Spontaneous Urticaria Patients Who Completed Preceding Studies With Remibrutinib

• ClinicalTrials.gov Identifier: NCT05513001
• Recruitment Status: Not yet recruiting
• First Posted: August 23, 2022
• Last Update Posted: October 5, 2022
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The purpose of this extension study is to collect long-term efficacy, safety and tolerability data on remibrutinib in a selected group of participants with Chronic Spontaneous Urticaria (CSU) who previously completed the treatment phase of remibrutinib preceding Phase 3 studies.

This study will also fulfill the Novartis commitment to provide post-trial access to participants who have completed the preceding Phase 3 studies, where applicable.

Condition or disease	Intervention/treatment	Phase
Chronic Spontaneous Urticaria (CSU)	Drug: LOU064 (blinded); Drug: Placebo; Drug: LOU064 (open label)	Phase 3

Expanded Access : Novartis Pharmaceuticals has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Detailed Description:

This is a global, multicenter, randomized, double-blind, placebo-controlled, randomized withdrawal Phase 3b extension study, followed by long-term open label treatment cycles to assess the efficacy, safety and tolerability of remibrutinib in adult participants with CSU inadequately controlled by H1-AH. The study comprises 2 Epochs. Epoch 1 is the initial study period for participants who completed preceding remibrutinib Phase 3 studies. Epoch 1 comprises of a 24-week randomized withdrawal period with remibrutinib or placebo for patients with UAS7<16 OR a 24 week Open-label treatment period with remibrutinib for patients with UAS7≥16.

Participants will be randomized in a 1:1 ratio to enter the double-blind placebo-controlled 24-week withdrawal phase. In case of relapse (UAS7≥16) in the blinded group, participants enter the (Re-)treatment period Epoch 1 and receive 24 weeks of Open-label treatment with remibrutinib. At the end of the (Re-)treatment period Epoch 1, participants will move to Epoch 2.

Epoch 2 is the second subsequent study period and consists of 24-week cycles that could either encompass treatment-free Observation and/or Open-label (Re-)treatment periods with remibrutinib, with or without background H1-AH.

In case of relapse (UAS7≥16) during an Observation period, participants enter the next (Re-)treatment period and receive 24 weeks of treatment with remibrutinib. Participants completing an Observation period 2/3/4/5 with a UAS7≤6 will complete the study. Participants with a UAS7 >6 -<16 can enter the next (Re-)treatment period if continuous treatment is considered necessary and beneficial for the individual participant. For participants with a UAS7<16 that enter the next (Re-)treatment period, remibrutinib monotherapy treatment (without background H1-AH) is required.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1021 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal and Open-label Extension Study Followed by Long-term Open-label Treatment Cycles to Assess the Efficacy, Safety and Tolerability of Remibrutinib (LOU064) in Adult Chronic Spontaneous Urticaria Patients Who Completed the Preceding Remibrutinib Phase 3 Studies
• Estimated Study Start Date: December 9, 2022
• Estimated Primary Completion Date: March 3, 2027
• Estimated Study Completion Date: March 3, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1: LOU064 (blinded); LOU064 (blinded) taken orally for 24 weeks, followed by cycles of either LOU064 (open-label) taken orally for a maximum of 5 cycles of 24 weeks each OR treatment-free observation cycles. Randomized in a 1:1 ratio (arm 1:arm 2)	Drug: LOU064 (blinded); LOU064 (blinded) active treatment; Other Name: remibrutinib; Drug: LOU064 (open label); LOU064 (open-label) active treatment; Other Name: remibrutinib
Placebo Comparator: Arm 2: LOU064 Placebo (blinded); LOU064 placebo (blinded) taken orally for 24 weeks, followed by cycles of either LOU064 (open-label) taken orally for a maximum of 5 cycles of 24 weeks each OR treatment-free observation cycles. Randomized in a 1:1 ratio (arm 1:arm 2)	Drug: Placebo; Placebo; Drug: LOU064 (open label); LOU064 (open-label) active treatment; Other Name: remibrutinib
Experimental: Arm 3: LOU064 (Open Label); LOU064 (open-label) taken orally for 24 weeks per treatment cycle (Arm 3)	Drug: LOU064 (open label); LOU064 (open-label) active treatment; Other Name: remibrutinib

Outcome Measures

Primary Outcome Measures :

1. Time to first composite event (i.e., relapse (UAS7≥16) [ Time Frame: 24 weeks ]

   The efficacy of remibrutinib in CSU participants with a UAS7<16 at Week 52 in the prior core study with respect to time to first of the three events: relapse or study treatment discontinuation due to lack of efficacy or intake of strongly confounding prohibited medication up to Week 24 compared to placebo. (Epoch 1)

   Time to first composite event (i.e., relapse (UAS7≥16), study treatment discontinuation due to lack of efficacy or intake of strongly confounding prohibited medication) during the randomized withdrawal period (Epoch 1)

Secondary Outcome Measures :

1. Number of treatment-emergent (serious and non-serious) adverse events [ Time Frame: 160 weeks ]

   The long-term safety and tolerability of remibrutinib

   Safety endpoints will include but not be limited to: occurrence of treatment-emergent (serious and non-serious) adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed.
• Male and female, adult participants ≥18 years of age.
• Participants who successfully completed the preceding core studies CLOU064A2301, CLOU064A2302, CLOU064A1301, CLOU064A2304 or CLOU064A2305 according to the respective protocols.
• Willing and able to adhere to the study protocol and visit schedule.

Exclusion Criteria:

• Significant bleeding risk or coagulation disorders.
• History of gastrointestinal bleeding.
• Requirement for anti-platelet medication.
• Requirement for anticoagulant medication.
• History or current hepatic disease.
• 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.

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05513001
• Other Study ID Numbers: CLOU064A2303B; 2022-001034-11 ( EudraCT Number )
• First Posted: August 23, 2022
• Last Update Posted: October 5, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Brutons Tyrosine Kinase (BTK) inhibitor; Chronic Spontaneous Urticaria; Urticaria activity score; Hives severity score; Itch severity score; Extension; Randomized withdrawal; Retreatment upon relapse; Remibrutinib

Additional relevant MeSH terms:

Urticaria; Chronic Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases