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24 Weeks Double-blind Randomized Placebo-controlled Trial to Evaluate Efficacy, PK, Safety of LOU064 in Adolescents (12 - <18) With CSU and Inadequate Response to H1-antihistamine Followed by Optional 3 Years Open-label Extension and an Optional 3 Years Safety Long-term Treatment-free Follow-up

Primary Purpose

Chronic Spontaneous Urticaria

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
LOU064 (blinded)
placebo
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 BTK inhibitor, Chronic spontaneous urticaria, Urticaria activity score, Hives severity score, Itch severity score

Eligibility Criteria

12 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Male and female adolescent participants aged ≥ 12 to < 18 years of age at the time of screening 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-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 according to local treatment guidelines 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) Key Exclusion criteria: Previous use of remibrutinib or other BTK inhibitors Significant bleeding risk or coagulation disorders. History of gastrointestinal bleeding. Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited. 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. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes 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 angioedema, 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

Sites / Locations

  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm 1: LOU064 (blinded)

Arm 2: LOU064 placebo (blinded)

Arm Description

LOU064 (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open-label) taken orally b.i.d. for up to 3 cycles of 24 weeks.

LOU064 placebo (blinded) taken orally b.i.d. for 12 weeks (randomized in a 2:1 ratio arm 1: arm 2), followed by LOU064 (open-label) taken orally b.i.d. for 12 weeks

Outcomes

Primary Outcome Measures

Change from baseline in UAS7
The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Negative change from baseline indicates improvement.
Change fron baseline in ISS7
Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement.
Change from baseline in HSS7
Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours). Negative change from baseline indicates improvement.

Secondary Outcome Measures

Cmax of remibrutinib
The maximum (peak) observed blood drug concentration after single dose administration
Tmax of remibrutinib
The time to reach maximum (peak) blood drug concentration after single dose administration
AUClast of remibrutinib
The Area Under the Curve (AUC) from pre-dose to the last measurable concentration sampling time
Absolute change from baseline in ISS7
Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement.
Absolute change from baseline in HSS7
Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours). Negative change from baseline indicates improvement.
Achievement of UAS7 ≤ 6 (yes/no)
Disease activity control is defined as UAS7 ≤ 6. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.
Achievement of UAS7 = 0 (yes/no)
Complete absence of hives and itch is defined as UAS7 = 0. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.
Absolute change from baseline in CDLQI score
The Children Dermatology life Quality Index (CDLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).
Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7 = 0 response
Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-105 where higher scores indicate increased angioedema activity.
Occurrence of treatment-emergent adverse events (AE) and serious adverse events (SAE) during the core period
To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the core period of the study.
Occurrence of treatment emergent AEs, and SAEs during the Open Label Extension (OLE) period
To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the OLE period of the study.

Full Information

First Posted
December 16, 2022
Last Updated
October 2, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05677451
Brief Title
24 Weeks Double-blind Randomized Placebo-controlled Trial to Evaluate Efficacy, PK, Safety of LOU064 in Adolescents (12 - <18) With CSU and Inadequate Response to H1-antihistamine Followed by Optional 3 Years Open-label Extension and an Optional 3 Years Safety Long-term Treatment-free Follow-up
Official Title
A Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy, Pharmacokinetics and Safety of Remibrutinib (LOU064) for 24 Weeks in Adolescents From 12 to Less Than 18 Years of Age With Chronic Spontaneous Urticaria Inadequately Controlled by H1-antihistamines Followed by an Optional Open-label Extension for up to Another 3 Years and an Optional Safety Long-term Treatment-free Follow-up Period for up to an Additional 3 Years
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 11, 2023 (Actual)
Primary Completion Date
October 30, 2025 (Anticipated)
Study Completion Date
November 17, 2031 (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
Yes
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, pharmacokinetics, and safety of remibrutinib vs. placebo in adolescents from 12 to < 18 years of age suffering from chronic spontaneous urticaria inadequately controlled by H1-antihistamines to collect long-term efficacy, safety and tolerability data on remibrutinib in adolescents after having completed 24 weeks of treatment to collect safety data in this population for up to three years after the last dose of treatment
Detailed Description
This trial consists of 3 different periods: 1/ the "core period", which is randomized and double-blind, during which 2/3 participants will receive remibrutinib and 1/3 will receive placebo for 12 weeks. After 12 weeks, all participants will receive remibrutinib for an additional 12 weeks. Total duration: approximately 34 weeks (10 site visits). 2/ an optional "open-label extension period" proposed to all participants who received remibrutinib for at least 4 months in the "core period". Depending on their CSU symptoms (as assessed by the doctor), participants will either receive remibrutinib for 24 weeks, or enter an observational treatment-free period for 1 year. If the CSU symptoms return during the observational period, the participants can switch to the treatment period at any time (decided by the doctor). At the end of the 24-week treatment period, if CSU is controlled, participants will enter the 1-year observational period, otherwise, they can continue with another cycle of 24-week remibrutinib treatment. The number of remibrutinib treatment or observational cycles will be limited to 3 times each. Total duration: from 1 year to approximately 3 years, and number of visits: from 3 to 10 (depending on the CSU symptoms). 3/ an optional "long-term treatment-free follow-up period" proposed to all participants who completed at least 4 months treatment in the "core period". No treatment will be given. Duration: 3 years with 1 site visit and up to 5 phone call follow-up visits. The primary clinical question of interest is what is the effect of remibrutinib treatment versus placebo on the change from baseline in UAS7, ISS7 and HSS7 scores after 12 weeks of treatment

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Spontaneous Urticaria
Keywords
BTK inhibitor, Chronic spontaneous urticaria, Urticaria activity score, Hives severity score, Itch severity score

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: LOU064 (blinded)
Arm Type
Experimental
Arm Description
LOU064 (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open-label) taken orally b.i.d. for up to 3 cycles of 24 weeks.
Arm Title
Arm 2: LOU064 placebo (blinded)
Arm Type
Placebo Comparator
Arm Description
LOU064 placebo (blinded) taken orally b.i.d. for 12 weeks (randomized in a 2:1 ratio arm 1: arm 2), followed by LOU064 (open-label) taken orally b.i.d. for 12 weeks
Intervention Type
Drug
Intervention Name(s)
LOU064 (blinded)
Other Intervention Name(s)
remibrutinib
Intervention Description
LOU064 (blinded) active treatment
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
matching active drug
Primary Outcome Measure Information:
Title
Change from baseline in UAS7
Description
The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Negative change from baseline indicates improvement.
Time Frame
Baseline, week 12
Title
Change fron baseline in ISS7
Description
Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement.
Time Frame
Baseline, Week 12
Title
Change from baseline in HSS7
Description
Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours). Negative change from baseline indicates improvement.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Cmax of remibrutinib
Description
The maximum (peak) observed blood drug concentration after single dose administration
Time Frame
At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
Title
Tmax of remibrutinib
Description
The time to reach maximum (peak) blood drug concentration after single dose administration
Time Frame
At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
Title
AUClast of remibrutinib
Description
The Area Under the Curve (AUC) from pre-dose to the last measurable concentration sampling time
Time Frame
At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
Title
Absolute change from baseline in ISS7
Description
Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement.
Time Frame
Baseline - Week 12
Title
Absolute change from baseline in HSS7
Description
Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours). Negative change from baseline indicates improvement.
Time Frame
Baseline - Week 12
Title
Achievement of UAS7 ≤ 6 (yes/no)
Description
Disease activity control is defined as UAS7 ≤ 6. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.
Time Frame
Week 12 and over time
Title
Achievement of UAS7 = 0 (yes/no)
Description
Complete absence of hives and itch is defined as UAS7 = 0. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.
Time Frame
Week 12 and over time
Title
Absolute change from baseline in CDLQI score
Description
The Children Dermatology life Quality Index (CDLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).
Time Frame
Week 12
Title
Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7 = 0 response
Description
Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-105 where higher scores indicate increased angioedema activity.
Time Frame
baseline - Week 12
Title
Occurrence of treatment-emergent adverse events (AE) and serious adverse events (SAE) during the core period
Description
To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the core period of the study.
Time Frame
28 weeks
Title
Occurrence of treatment emergent AEs, and SAEs during the Open Label Extension (OLE) period
Description
To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the OLE period of the study.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Male and female adolescent participants aged ≥ 12 to < 18 years of age at the time of screening 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-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 according to local treatment guidelines 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) Key Exclusion criteria: Previous use of remibrutinib or other BTK inhibitors Significant bleeding risk or coagulation disorders. History of gastrointestinal bleeding. Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited. 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. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes 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 angioedema, 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
229899
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Adana
ZIP/Postal Code
01050
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Individual Site Status
Recruiting

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

24 Weeks Double-blind Randomized Placebo-controlled Trial to Evaluate Efficacy, PK, Safety of LOU064 in Adolescents (12 - <18) With CSU and Inadequate Response to H1-antihistamine Followed by Optional 3 Years Open-label Extension and an Optional 3 Years Safety Long-term Treatment-free Follow-up

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