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A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1 Antihistamines (REMIX-1)

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ClinicalTrials.gov Identifier: NCT05030311
Recruitment Status : Recruiting
First Posted : September 1, 2021
Last Update Posted : February 16, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to establish the efficacy, safety, and tolerability of remibrutinib (LOU064) in adult participants suffering from chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines in comparison to placebo.

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

Detailed Description:

This is a global, multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase 3 study investigating the safety, tolerability, and efficacy of remibrutinib in adult participants with CSU inadequately controlled by second generation H1-antihistamines.

Inadequate control of CSU by H1-antihistamines is defined as:

  • The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite the use of second generation H1-antihistamines 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).

The study consists of four periods, the total study duration is up to 60 weeks. Screening period of up to 4 weeks, double-blind treatment period of 24 weeks, open-label treatment period of 28 weeks and 4 weeks of treatment-free follow up.

Eligible participants will be randomly assigned to the treatment arms in a 2:1 ratio. The study population will consist of approximately 450 female and male adult participants (300 in the active arm and 150 in the placebo arm) with CSU inadequately controlled by second generation H1-antihistamines at least at locally label approved dose.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study of Remibrutinib (LOU064) to Investigate the Efficacy, Safety and Tolerability for 52 Weeks in Adult Chronic Spontaneous Urticaria (CSU) Patients Inadequately Controlled by H1-antihistamines
Actual Study Start Date : November 30, 2021
Estimated Primary Completion Date : February 2, 2024
Estimated Study Completion Date : March 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1: LOU064 (blinded)
LOU064 (blinded) taken orally for 24 weeks, followed by LOU064 (open-label) taken orally open label for 28 weeks. Randomized in a 2:1 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 LOU064 (open-label) taken orally for 28 weeks. Randomized in a 2:1 ratio (arm 1:arm 2).
Drug: Placebo
Placebo

Drug: LOU064 (open-label)
LOU064 (open-label) active treatment
Other Name: remibrutinib




Primary Outcome Measures :
  1. Change from baseline in UAS7 (Scenario 1 with UAS7 as primary efficacy endpoint) [ Time Frame: 12 weeks ]

    To demonstrate that remibrutinib is superior to placebo in CSU with respect to change from baseline in UAS7 at Week 12 by assessing absolute change from baseline in weekly Urticaria Activity Score (UAS7) at week 12.

    The UAS7 is a simple scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42, and a minimum possible score of 0.


  2. Absolute change in ISS7 and absolute change in HSS7 (Scenario 2 with ISS7 and HSS7 as co-primary efficacy endpoints) [ Time Frame: 12 weeks ]

    To demonstrate that remibrutinib is superior to placebo in CSU with respect to change from baseline in ISS7 and HSS7 at Week 12 by assessing absolute change from baseline in weekly Itch Severity Score (ISS7) and weekly Hive Severity Score (HSS7) at week 12.

    The ISS7 and HSS7 combined together make up the UAS7 scoring system to evaluate urticaria signs and symptoms. The HSS7 score is the wheal/hives severity score for 7 days and the ISS7 is the itch severity score for 7 days, both these scores range from 0 to 21.



Secondary Outcome Measures :
  1. Change from baseline in UAS7 (only in scenario 2) [ Time Frame: 12 weeks ]
    To demonstrate that remibrutinib is superior to placebo in CSU with respect to change from baseline in UAS7 at Week 12 by assessing absolute change from baseline in UAS7 at week 12.

  2. Sustained disease activity control (UAS7 ≤6) [ Time Frame: 12 weeks ]
    To demonstrate that remibrutinib treated participants maintain disease activity control (defined as UAS7≤6) for more weeks compared to placebo treated participants over 12 weeks by assessing cumulative number of weeks with an UAS7 ≤ 6 response between baseline and Week 12.

  3. Complete absence of hives and itch (UAS7 = 0) [ Time Frame: 12 weeks ]
    To demonstrate that a greater proportion of participants achieve complete absence of hives and itch (UAS7 = 0) at Week 12 who are treated with remibrutinib compared to placebo-treated participants by assessing achievement of UAS7 at week 12.

  4. Reduction of weekly ISS score (only in scenario 1) [ Time Frame: 12 weeks ]
    To demonstrate the superiority of remibrutinib treated participants with respect to a reduction from baseline in the weekly itch severity score at Week 12 compared to placebo-treated participants by assessing absolute change from baseline in ISS7 score.

  5. Reduction of weekly HSS score (only in scenario 1) [ Time Frame: 12 weeks ]
    To demonstrate the superiority of remibrutinib treated participants with respect to a reduction from baseline in the weekly hive severity score at Week 12 compared to placebo-treated participants by assessing absolute change from baseline in HSS7 score.

  6. Early onset of disease control (UAS7 ≤ 6 at week 2) [ Time Frame: 2 weeks ]
    To demonstrate that a greater proportion of participants achieve UAS7 ≤ 6 at Week 2 who are treated with remibrutinib compared to placebo-treated participants by assessing achievement of UAS ≤ 6 at week 2.

  7. Disease activity control (UAS7 ≤ 6) [ Time Frame: 12 weeks ]
    To demonstrate that a greater proportion of participants achieve disease activity control (UAS7 ≤ 6) at Week 12 who are treated with remibrutinib compared to placebo-treated participants by assessing achievement of UA7 ≤ 6 at week 12.

  8. Achievement of DLQI = 0 - 1 [ Time Frame: 12 weeks ]
    To demonstrate that a greater proportion of participants who are treated with remibrutinib achieve DLQI = 0-1 at Week 12 compared to placebo-treated participants by assessing achievement of DLQI = 0 - 1 at week 12.

  9. Number of weeks without angioedema (AAS = 0) [ Time Frame: 12 weeks ]
    To demonstrate that remibrutinib treated participants have more angioedema occurrence-free weeks over 12 weeks compared with placebo-treated participants by assessing the cumulative number of weeks with an AAS = 0 response between baseline and week 12.

  10. Number of participants with Adverse Events [ Time Frame: 56 weeks ]
    To demonstrate the safety and tolerability of remibrutinib by assessing the occurrence of treatment emergent adverse events and serious adverse events during the study.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Signed informed consent must be obtained prior to participation in the study.
  • Male and female adult participants ≥18 years of age.
  • CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation).
  • Diagnosis of CSU inadequately controlled by second generation H1 antihistamines 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-antihistamines 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 (either at screening and/or at randomization; or documented in the participants medical history).
  • 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:

  • Participants having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria
  • Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, or drug-induced urticaria
  • Any other skin disease associated with chronic itching that might influence in the investigator's opinion the study evaluations and results, e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis
  • Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York heart association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to Visit 1), 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
  • Significant bleeding risk or coagulation disorders
  • History of gastrointestinal bleeding, e.g. in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant (e.g. requiring hospitalization or blood transfusion)
  • Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel. The use of dual anti-platelet therapy (e.g. acetylsalicylic acid + clopidogrel) is prohibited.
  • Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOAC))
  • History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05030311


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05030311    
Other Study ID Numbers: CLOU064A2301
First Posted: September 1, 2021    Key Record Dates
Last Update Posted: February 16, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect 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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
BTK inhibitor
Chronic spontaneous urticaria
Urticaria activity score
Hives severity score
Itch severity score
CSU
Additional relevant MeSH terms:
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Urticaria
Chronic Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases