search
Back to results

A Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib in Comparison to Placebo and With Omalizumab as Active Control in CSU Adult Patients.

Primary Purpose

Chronic Spontaneous Urticaria

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Remibrutinib
Placebo to remibrutinib
Placebo to omalizumab
Omalizumab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Spontaneous Urticaria focused on measuring CSU, urticaria, LOU064, omalizumab, remibrutinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male and female adult participants ≥18 years of age at the time of signing the informed consent. CSU duration for ≥ 6 months prior to screening. 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). Documentation of hives within three months before randomization. Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol. 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: Prior exposure to ligelizumab, omalizumab and other biologics with any effect in CSU, including anti-IgE therapies. Significant bleeding risk or coagulation disorders. History of gastrointestinal bleeding. Requirement for anti-platelet or anti-coagulant 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. Evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines. Documented history of anaphylaxis.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Placebo Comparator

    Placebo Comparator

    Active Comparator

    Arm Label

    Remibrutinib

    Placebo to remibrutinib

    Placebo to omalizumab

    Omalizumab

    Arm Description

    Participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks.

    Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.

    Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.

    participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.

    Outcomes

    Primary Outcome Measures

    Absolute change from baseline in Weekly Urticaria Activity Score (UAS7)
    The UAS7 is the sum of the Weekly Hives Severity Score (HSS7 score) and the Weekly Itch Severity Score (ISS7 score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).

    Secondary Outcome Measures

    Achievement of UAS7=0 (yes/no)
    Complete UAS7 response is UAS7 = 0
    Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score
    The severity of the itch will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.
    Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score
    The hives (wheals) severity score, defined by number of hives, will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (> 12 hives/12 hours). A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.
    Occurrence of treatment-emergent adverse events and serious adverse events (SAEs)
    To demonstrate the safety and tolerability of remibrutinib (25 mg b.i.d.)

    Full Information

    First Posted
    September 7, 2023
    Last Updated
    September 20, 2023
    Sponsor
    Novartis Pharmaceuticals
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT06042478
    Brief Title
    A Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib in Comparison to Placebo and With Omalizumab as Active Control in CSU Adult Patients.
    Official Title
    A Global, Multicenter, Randomized, Double-blind, Double-dummy, Parallel-group, Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib 25 mg b.i.d. in Comparison to Placebo With Omalizumab 300 mg Every 4 Weeks as Active Control Over 52 Weeks in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by Second-generation H1-antihistamines
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 24, 2023 (Anticipated)
    Primary Completion Date
    August 15, 2025 (Anticipated)
    Study Completion Date
    June 23, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Novartis Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this trial is to assess the efficacy, safety and tolerability of remibrutinib (LOU064) 25 milligrams (mg) twice a day (b.i.d.) over placebo for 24 weeks and in comparison to omalizumab 300 mg every 4 weeks (q4w) for 52 weeks in participants with chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines (H1-AH).
    Detailed Description
    The study consists of three periods, and the total study duration is up to 72 weeks. Approximately 468 adult participants with CSU are expected to be randomized in the study. Screening period: A screening period of up to 4 weeks will allow for the assessment of eligibility, determination of baseline disease activity and wash-out of prohibited medications. Treatment period: The treatment period will be double-dummy and double-blind, with placebo injections matching omalizumab 300 mg s.c. given to participants in the remibrutinib arm and placebo tablets matching remibrutinib 25 mg given to participants in the omalizumab arm (double-dummy). At the randomization visit, eligible participants will be randomized to one of four treatment arms. Follow-up period: There will be a 16-week, treatment-free, safety follow-up period (for participants who do not roll-over to the extension study). All participants will be on a stable, local label-approved standard dose of a second-generation H1-AH ("background therapy") throughout the entire study (starting a minimum of 7 days prior to randomization until the end of the study). In addition, to treat unbearable symptoms of CSU flare-ups, participants will be allowed to use a different second-generation H1-AH on an as-needed basis ("rescue therapy").

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Spontaneous Urticaria
    Keywords
    CSU, urticaria, LOU064, omalizumab, remibrutinib

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    At the randomization visit, eligible participants will be randomized to one of four treatment arms in a 2:1:1:2 ratio: Remibrutinib 25 mg b.i.d. arm: participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks Placebo to remibrutinib arm: participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w. Placebo to omalizumab arm: participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. Omalizumab 300 mg every 4 weeks arm: participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    468 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Remibrutinib
    Arm Type
    Experimental
    Arm Description
    Participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks.
    Arm Title
    Placebo to remibrutinib
    Arm Type
    Placebo Comparator
    Arm Description
    Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.
    Arm Title
    Placebo to omalizumab
    Arm Type
    Placebo Comparator
    Arm Description
    Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.
    Arm Title
    Omalizumab
    Arm Type
    Active Comparator
    Arm Description
    participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Remibrutinib
    Intervention Description
    Active treatment
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to remibrutinib
    Intervention Description
    Placebo followed by active treatment
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to omalizumab
    Intervention Description
    Placebo followed by active comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Omalizumab
    Intervention Description
    Active comparator
    Primary Outcome Measure Information:
    Title
    Absolute change from baseline in Weekly Urticaria Activity Score (UAS7)
    Description
    The UAS7 is the sum of the Weekly Hives Severity Score (HSS7 score) and the Weekly Itch Severity Score (ISS7 score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).
    Time Frame
    Week 12
    Secondary Outcome Measure Information:
    Title
    Achievement of UAS7=0 (yes/no)
    Description
    Complete UAS7 response is UAS7 = 0
    Time Frame
    Week 12
    Title
    Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score
    Description
    The severity of the itch will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.
    Time Frame
    Week 12
    Title
    Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score
    Description
    The hives (wheals) severity score, defined by number of hives, will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (> 12 hives/12 hours). A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.
    Time Frame
    Week 12
    Title
    Occurrence of treatment-emergent adverse events and serious adverse events (SAEs)
    Description
    To demonstrate the safety and tolerability of remibrutinib (25 mg b.i.d.)
    Time Frame
    up to 68 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male and female adult participants ≥18 years of age at the time of signing the informed consent. CSU duration for ≥ 6 months prior to screening. 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). Documentation of hives within three months before randomization. Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol. 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: Prior exposure to ligelizumab, omalizumab and other biologics with any effect in CSU, including anti-IgE therapies. Significant bleeding risk or coagulation disorders. History of gastrointestinal bleeding. Requirement for anti-platelet or anti-coagulant 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. Evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines. Documented history of anaphylaxis.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals
    Phone
    +41613241111
    Email
    novartis.email@novartis.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Novartis Pharmaceuticals
    Organizational Affiliation
    Novartis Pharmaceuticals
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing 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

    Learn more about this trial

    A Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib in Comparison to Placebo and With Omalizumab as Active Control in CSU Adult Patients.

    We'll reach out to this number within 24 hrs