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出境医 / 临床实验 / Dose-finding Study to Evaluate Efficacy and Safety of LOU064 in Patients With CSU Inadequately Controlled by H1-antihistamines

Dose-finding Study to Evaluate Efficacy and Safety of LOU064 in Patients With CSU Inadequately Controlled by H1-antihistamines

Study Description
Brief Summary:
This is a multicenter, randomized, double-blind and placebo-controlled phase 2b dose-finding study to assess the efficacy and safety of LOU064 in adults chronic spontaneous urticaria (CSU) patients inadequately controlled by H1-antihistamines

Condition or disease Intervention/treatment Phase
Chronic Spontaneous Urticaria Drug: LOU064 Arm 1 Drug: LOU064 Arm 2 Drug: LOU064 Arm 3 Drug: LOU064 Arm 4 Drug: LOU064 Arm 5 Drug: LOU064 Arm 6 Drug: Placebo arm Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 311 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo- Controlled Phase 2b Dose-finding Study to Investigate the Efficacy, Safety and Tolerability of LOU064 in Adult Chronic Spontaneous Urticaria (CSU) Patients Inadequately Controlled by H1-antihistamines
Actual Study Start Date : June 6, 2019
Actual Primary Completion Date : January 14, 2021
Actual Study Completion Date : April 15, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: LOU064 Arm 1
Participants will be asked to take LOU064 low dose once daily
 Drug: LOU064 Arm 1
Low dose of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
Experimental: LOU064 Arm 2
Participants will be asked to take LOU064 medium dose once daily
 Drug: LOU064 Arm 2
Medium dose of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
Experimental: LOU064 Arm 3
Participants will be asked to take LOU064 high dose once daily
 Drug: LOU064 Arm 3
High dose of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
Experimental: LOU064 Arm 4
Participants will be asked to take LOU064 low dose twice daily
 Drug: LOU064 Arm 4
Low dose of LOU064 orally, twice daily from Day 1 to 85
Experimental: LOU064 Arm 5
Participants will be asked to take LOU064 medium dose twice daily
 Drug: LOU064 Arm 5
Medium dose of LOU064 orally, twice daily from Day 1 to 85
Experimental: LOU064 Arm 6
Participants will be asked to take LOU064 high dose twice daily
 Drug: LOU064 Arm 6
High dose of LOU064 orally, twice daily from Day 1 to 85
Placebo Comparator: Placebo Arm
Participants will be asked to take matching placebo twice daily
 Drug: Placebo arm
Matching placebo, orally, twice daily from Day 1 to 85
Outcome Measures
Primary Outcome Measures :
  1. Change from baseline in weekly Urticaria Activity Score (UAS7) [ Time Frame: Week 4 ]

    The primary objective of this study is to characterize the dose-response relationship of LOU064 administered once or twice daily in subjects with CSU with respect to change from baseline in UAS7 at Week 4.

    The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).



Secondary Outcome Measures :
  1. Change from baseline in weekly Urticaria Activity Score (UAS7) [ Time Frame: Week 12 ]
    The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).

  2. Change from baseline in weekly Urticaria Activity Score (UAS7) [ Time Frame: Over time from week 1 to week 16 ]
    The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).

  3. Complete absence of hives and itch (UAS7=0) [ Time Frame: Over time from week 1 to week 16 ]

    The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).

    A complete absence of hives and itches over a week is defined as UAS7=0.


  4. Disease control (UAS7<=6) [ Time Frame: Over time from week 1 to week 16 ]

    The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).

    Disease control is defined as UAS7<=6.


  5. Cumulative number of weeks with an AAS7=0 response [ Time Frame: Baseline to Week 12 ]
    The AAS is a validated tool to assess occurrence of episodes of angioedema. If the subject reports the occurrence of angioedema ("opening question") with "no", AAS score for this day is 0. If "yes" is the answer to the opening question, the subject will continue to answer questions about the duration, severity and impact on daily functioning and appearance of the angioedema. The AAS7 is a weekly AAS score (AAS7). Minimum and maximum possible AAS7 scores are 0-105. Higher score means higher severity.

  6. DLQI score of 0 or 1 [ Time Frame: Week 4 and Week 12 ]
    The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL). A DLQI score of 0 or 1 means that there is no impact of a skin disease on the patient's life.

  7. Change from baseline in DLQI score [ Time Frame: Week 4 and Week 12 ]
    The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL).

  8. Area under the blood concentration-time curve (AUC) of LOU064 [ Time Frame: Week 4 and Week 12 ]
    Assessment of the area under the blood concentration-time curve (AUC)up to four hours following oral administration at Week 4 and Week 12 .

  9. Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Over time from week 1 to week 16 ]
    Safety endpoints will include but not be limited to: occurrence of treatment emergent (serious and non-serious) adverse events.

  10. Observed maximum blood concentration (Cmax) of LOU064 [ Time Frame: Week 4 and Week 12 ]
    Assessment of the observed maximum blood concentration (Cmax) of LOU064 following drug administration at Week 4 and Week 12 .

  11. Time to reach the maximum concentration (Tmax) of LOU064 [ Time Frame: Week 4 and Week 12 ]
    Assessment of the time to reach the maximum concentration (Tmax) of LOU064 following drug administration at Week 4 and Week 12 .


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects aged ≥18 years of age
  • CSU diagnosis for ≥ 6 months prior to screening
  • Presence of itch and hives for ≥6 consecutive weeks prior to screening in spite of use of non-sedating H1-antihistamines according to local Treatment guidelines during this time period
  • UAS7 score (range 0-42) ≥16 and HSS7 score (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1)
  • Willing and able to complete an Urticaria Participant Daily eDiary (UPDD) for the duration of the study

Exclusion Criteria:

  • Hypersensitivity to any of the study treatments
  • Clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria)
  • Other diseases with symptoms of urticaria or angioedema
  • Other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results,
  • Known or suspected history of an ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (eg tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis), HIV, Hepatitis B/C.
  • Pregnant or nursing (lactating) women
  • Women of child-bearing potential not using highly effective methods of contraception

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations
Show Show 82 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Tracking Information
First Submitted Date  ICMJE April 12, 2019
First Posted Date  ICMJE April 24, 2019
Last Update Posted Date May 17, 2021
Actual Study Start Date  ICMJE June 6, 2019
Actual Primary Completion Date January 14, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2019) 		Change from baseline in weekly Urticaria Activity Score (UAS7) [ Time Frame: Week 4 ]
The primary objective of this study is to characterize the dose-response relationship of LOU064 administered once or twice daily in subjects with CSU with respect to change from baseline in UAS7 at Week 4. The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
  • Change from baseline in weekly Urticaria Activity Score (UAS7) [ Time Frame: Week 12 ]
    The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).
  • Change from baseline in weekly Urticaria Activity Score (UAS7) [ Time Frame: Over time from week 1 to week 16 ]
    The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).
  • Complete absence of hives and itch (UAS7=0) [ Time Frame: Over time from week 1 to week 16 ]
    The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity). A complete absence of hives and itches over a week is defined as UAS7=0.
  • Disease control (UAS7<=6) [ Time Frame: Over time from week 1 to week 16 ]
    The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity). Disease control is defined as UAS7<=6.
  • Cumulative number of weeks with an AAS7=0 response [ Time Frame: Baseline to Week 12 ]
    The AAS is a validated tool to assess occurrence of episodes of angioedema. If the subject reports the occurrence of angioedema ("opening question") with "no", AAS score for this day is 0. If "yes" is the answer to the opening question, the subject will continue to answer questions about the duration, severity and impact on daily functioning and appearance of the angioedema. The AAS7 is a weekly AAS score (AAS7). Minimum and maximum possible AAS7 scores are 0-105. Higher score means higher severity.
  • DLQI score of 0 or 1 [ Time Frame: Week 4 and Week 12 ]
    The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL). A DLQI score of 0 or 1 means that there is no impact of a skin disease on the patient's life.
  • Change from baseline in DLQI score [ Time Frame: Week 4 and Week 12 ]
    The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL).
  • Area under the blood concentration-time curve (AUC) of LOU064 [ Time Frame: Week 4 and Week 12 ]
    Assessment of the area under the blood concentration-time curve (AUC)up to four hours following oral administration at Week 4 and Week 12 .
  • Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Over time from week 1 to week 16 ]
    Safety endpoints will include but not be limited to: occurrence of treatment emergent (serious and non-serious) adverse events.
  • Observed maximum blood concentration (Cmax) of LOU064 [ Time Frame: Week 4 and Week 12 ]
    Assessment of the observed maximum blood concentration (Cmax) of LOU064 following drug administration at Week 4 and Week 12 .
  • Time to reach the maximum concentration (Tmax) of LOU064 [ Time Frame: Week 4 and Week 12 ]
    Assessment of the time to reach the maximum concentration (Tmax) of LOU064 following drug administration at Week 4 and Week 12 .
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-finding Study to Evaluate Efficacy and Safety of LOU064 in Patients With CSU Inadequately Controlled by H1-antihistamines
Official Title  ICMJE A Multicenter, Randomized, Double-blind, Placebo- Controlled Phase 2b Dose-finding Study to Investigate the Efficacy, Safety and Tolerability of LOU064 in Adult Chronic Spontaneous Urticaria (CSU) Patients Inadequately Controlled by H1-antihistamines
Brief Summary This is a multicenter, randomized, double-blind and placebo-controlled phase 2b dose-finding study to assess the efficacy and safety of LOU064 in adults chronic spontaneous urticaria (CSU) patients inadequately controlled by H1-antihistamines
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Spontaneous Urticaria
Intervention  ICMJE
  • Drug: LOU064 Arm 1
    Low dose of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
  • Drug: LOU064 Arm 2
    Medium dose of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
  • Drug: LOU064 Arm 3
    High dose of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
  • Drug: LOU064 Arm 4
    Low dose of LOU064 orally, twice daily from Day 1 to 85
  • Drug: LOU064 Arm 5
    Medium dose of LOU064 orally, twice daily from Day 1 to 85
  • Drug: LOU064 Arm 6
    High dose of LOU064 orally, twice daily from Day 1 to 85
  • Drug: Placebo arm
    Matching placebo, orally, twice daily from Day 1 to 85
Study Arms  ICMJE
  • Experimental: LOU064 Arm 1
    Participants will be asked to take LOU064 low dose once daily
    Intervention: Drug: LOU064 Arm 1
  • Experimental: LOU064 Arm 2
    Participants will be asked to take LOU064 medium dose once daily
    Intervention: Drug: LOU064 Arm 2
  • Experimental: LOU064 Arm 3
    Participants will be asked to take LOU064 high dose once daily
    Intervention: Drug: LOU064 Arm 3
  • Experimental: LOU064 Arm 4
    Participants will be asked to take LOU064 low dose twice daily
    Intervention: Drug: LOU064 Arm 4
  • Experimental: LOU064 Arm 5
    Participants will be asked to take LOU064 medium dose twice daily
    Intervention: Drug: LOU064 Arm 5
  • Experimental: LOU064 Arm 6
    Participants will be asked to take LOU064 high dose twice daily
    Intervention: Drug: LOU064 Arm 6
  • Placebo Comparator: Placebo Arm
    Participants will be asked to take matching placebo twice daily
    Intervention: Drug: Placebo arm
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 9, 2021) 		311
Original Estimated Enrollment  ICMJE
 (submitted: April 23, 2019) 		308
Actual Study Completion Date  ICMJE April 15, 2021
Actual Primary Completion Date January 14, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male and female subjects aged ≥18 years of age
  • CSU diagnosis for ≥ 6 months prior to screening
  • Presence of itch and hives for ≥6 consecutive weeks prior to screening in spite of use of non-sedating H1-antihistamines according to local Treatment guidelines during this time period
  • UAS7 score (range 0-42) ≥16 and HSS7 score (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1)
  • Willing and able to complete an Urticaria Participant Daily eDiary (UPDD) for the duration of the study

Exclusion Criteria:

  • Hypersensitivity to any of the study treatments
  • Clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria)
  • Other diseases with symptoms of urticaria or angioedema
  • Other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results,
  • Known or suspected history of an ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (eg tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis), HIV, Hepatitis B/C.
  • Pregnant or nursing (lactating) women
  • Women of child-bearing potential not using highly effective methods of contraception

Other protocol-defined inclusion/exclusion criteria may apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Belgium,   Canada,   Czechia,   Denmark,   France,   Germany,   Hungary,   Japan,   Netherlands,   Poland,   Russian Federation,   Slovakia,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03926611
Other Study ID Numbers  ICMJE CLOU064A2201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
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
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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