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

Novartis

Status and phase: Active, not recruiting; Phase 3

Conditions: Chronic Spontaneous Urticaria

Treatments: Drug: LOU064 (blinded); Drug: Placebo; Drug: LOU064 (open label)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05513001

CLOU064A2303B

2022-001034-11 (EudraCT Number)

Details and patient eligibility

About

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 core 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.

Full description

This is a Phase 3b multicenter, double-blind, placebo-controlled, randomized withdrawal, and open-label extension study to evaluate the efficacy and safety of remibrutinib 25 mg twice daily (b.i.d.) in adult CSU participants who have completed one of the preceding Phase 3 core studies. The study comprises 2 Epochs:

Epoch 1 is the initial study period and includes participants from preceding Phase 3 studies. It consists of a 24-week randomized withdrawal period where participants receive either remibrutinib 25 mg b.i.d. or placebo if their UAS7 score is less than 16. For those with a UAS7 score of 16 or higher, there is a 24-week open-label treatment period with remibrutinib 25 mg b.i.d. Participants are randomized 1:1 to the double-blind placebo-controlled withdrawal phase. All participants will continue their background H1-AH treatment. If participants relapse (UAS7 ≥ 16) in the blinded group, they enter the (Re-)treatment period of Epoch 1 and receive 24 weeks of open-label treatment with remibrutinib 25 mg b.i.d. After this period, they move to Epoch 2.

Epoch 2 is the second subsequent study period and consists of 24-week cycles that may include treatment-free observation and/or open-label (Re-)treatment periods with remibrutinib 25 mg b.i.d., with or without background H1-AH, at the investigator's discretion. Participants from future Phase 3 remibrutinib studies may also join Epoch 2 if approved. If participants relapse (UAS7 ≥ 16) during an observation period, they enter the next (Re-)treatment period for 24 weeks of treatment with remibrutinib 25 mg b.i.d. Participants completing an observation period with a UAS7 ≤ 6 will complete the study with an end-of-study (EOS) visit. Those with a UAS7 > 6 but < 16 can enter the next (Re-)treatment period if continuous treatment is deemed necessary. Participants with a UAS7 < 16 in the previous treatment period will receive remibrutinib monotherapy (without background H1-AH). If treatment continuation is not necessary, they complete the EOS visit and leave the study. Participants with a UAS7 ≥ 16 during the observation period will enter the corresponding (Re-)treatment period to continue treatment.

Throughout Epoch 2, the use of background H1-AH is at the investigator's discretion, except for participants with a UAS7 < 16 in the previous treatment period, who will be treated with remibrutinib monotherapy.

Enrollment: 696 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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696 participants in 3 patient groups, including a placebo group

Arm 1: LOU064 (blinded)

Experimental group

Description:

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)

Treatment:

Drug: LOU064 (open label)

Drug: LOU064 (blinded)

Arm 2: LOU064 Placebo (blinded)

Placebo Comparator group

Description:

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)

Treatment:

Drug: LOU064 (open label)

Drug: Placebo

Arm 3: LOU064 (Open Label)

Experimental group

Description:

LOU064 (open-label) taken orally for 24 weeks per treatment cycle (Arm 3)

Treatment:

Drug: LOU064 (open label)