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
Overview
- Phase
- Phase 3
- Intervention
- LOU064 (blinded)
- Conditions
- Chronic Spontaneous Urticaria
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 696
- Locations
- 250
- Primary Endpoint
- Time to first composite event (i.e., relapse (UAS7≥16)
- Status
- Active, Not Recruiting
- Last Updated
- last month
Overview
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 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.
Detailed 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.
Investigators
Eligibility 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.
Arms & Interventions
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)
Intervention: LOU064 (blinded)
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)
Intervention: LOU064 (open label)
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)
Intervention: Placebo
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)
Intervention: LOU064 (open label)
Arm 3: LOU064 (Open Label)
LOU064 (open-label) taken orally for 24 weeks per treatment cycle (Arm 3)
Intervention: LOU064 (open label)
Outcomes
Primary Outcomes
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) Urticaria Activity Score (UAS7) describes the number of hives with 0 being No Hives and 3 is most severe. The final score is calculated by adding together daily scores which can range from 0-6 for 7 days. The resulting maximum score is then 42.
Secondary Outcomes
- Number of participants with treatment-emergent (serious and non-serious) adverse events(160 weeks)