An Extension Study of Long-term Efficacy, Safety and Tolerability of Remibrutinib in Chronic Spontaneous Urticaria Patients Who Completed Preceding Studies With Remibrutinib
- Conditions
- Chronic Spontaneous Urticaria
- Interventions
- Drug: LOU064 (blinded)Drug: PlaceboDrug: LOU064 (open label)
- Registration Number
- NCT05513001
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 695
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: LOU064 (blinded) 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) Arm 1: LOU064 (blinded) LOU064 (open label) 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) Arm 2: LOU064 Placebo (blinded) Placebo 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) Arm 2: LOU064 Placebo (blinded) LOU064 (open label) 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) Arm 3: LOU064 (Open Label) LOU064 (open label) LOU064 (open-label) taken orally for 24 weeks per treatment cycle (Arm 3)
- Primary Outcome Measures
Name Time Method Time to first composite event (i.e., relapse (UAS7≥16) 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 Outcome Measures
Name Time Method Number of participants with treatment-emergent (serious and non-serious) adverse events 160 weeks Occurrence of treatment-emergent (serious and non-serious) adverse events
Trial Locations
- Locations (45)
Allervie Clinical Research
🇺🇸Birmingham, Alabama, United States
Cahaba Derm and skin hlth ctr 27
🇺🇸Birmingham, Alabama, United States
Research Solutions of Arizona
🇺🇸Litchfield Park, Arizona, United States
Acuro Research Inc
🇺🇸Little Rock, Arkansas, United States
Arkansas Research Trials
🇺🇸North Little Rock, Arkansas, United States
Kern Research
🇺🇸Bakersfield, California, United States
Antelope Valley Clinical Trials
🇺🇸Lancaster, California, United States
Allergy and Asthma Consultants
🇺🇸Redwood City, California, United States
Asthma and Allergy Associates P C
🇺🇸Colorado Springs, Colorado, United States
Colorado Allergy and Asthma Ctr PC
🇺🇸Denver, Colorado, United States
UCONN Health Dermatology
🇺🇸Farmington, Connecticut, United States
Florida Ctr Allergy Asthma Research
🇺🇸Aventura, Florida, United States
Finlay Medical Research
🇺🇸Greenacres City, Florida, United States
Miami Dade Medical Research
🇺🇸Miami, Florida, United States
Sarasota Clinical Research
🇺🇸Sarasota, Florida, United States
Allergy and Asthma Diagnostic Treatment Center
🇺🇸Tallahassee, Florida, United States
AeroAllergy Research Laboratories of Savannah Inc
🇺🇸Savannah, Georgia, United States
Treasure Valley Medical Research
🇺🇸Boise, Idaho, United States
Endeavor Health
🇺🇸Glenview, Illinois, United States
Asthma and Allergy Center of Chicago S C
🇺🇸River Forest, Illinois, United States
Deaconess Clin Allerg Res Inst
🇺🇸Evansville, Indiana, United States
The Indiana Clinical Trials Center
🇺🇸Plainfield, Indiana, United States
Allergy and Asthma Specialist P S C
🇺🇸Owensboro, Kentucky, United States
John Hopkins University
🇺🇸Baltimore, Maryland, United States
Institute for Asthma and Allergy PC
🇺🇸Chevy Chase, Maryland, United States
The Clinical Research Center
🇺🇸Saint Louis, Missouri, United States
Somnos Clinical Research
🇺🇸Lincoln, Nebraska, United States
Allergy Asthma Assoc Monmouth
🇺🇸Little Silver, New Jersey, United States
Oakview Dermatology
🇺🇸Athens, Ohio, United States
Optimed Research LLC
🇺🇸Columbus, Ohio, United States
CR Services Acquisition US
🇺🇸Dublin, Ohio, United States
Toledo Institute of Clinical Research
🇺🇸Toledo, Ohio, United States
Allergy Asthma and Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
Vital Prospects Clinical Research Institute
🇺🇸Tulsa, Oklahoma, United States
Allergy and Clinical Immunology Associates
🇺🇸Pittsburgh, Pennsylvania, United States
National Allergy and Asthma Research LLS
🇺🇸North Charleston, South Carolina, United States
Orion Clinical Research
🇺🇸Austin, Texas, United States
Western Sky Medical Research
🇺🇸El Paso, Texas, United States
RFSA Dermatology
🇺🇸San Antonio, Texas, United States
Allergy Associates of Utah
🇺🇸Sandy, Utah, United States
Bellingham Asthma Allergy and Immunology
🇺🇸Bellingham, Washington, United States
Seattle Allergy and Asthma Rsch
🇺🇸Seattle, Washington, United States
Allergy Asthma and amp Sinus Ctr S C
🇺🇸Greenfield, Wisconsin, United States
Novartis Investigative Site
🇬🇧Cardiff, United Kingdom
Alma Cruz-Santana Private Practice
🇵🇷Carolina, Puerto Rico