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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03926611
Recruitment Status : Completed
First Posted : April 24, 2019
Results First Posted : February 16, 2022
Last Update Posted : April 29, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This was 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

Detailed Description:
This was a global Phase 2b multicenter, randomized, double-blind, parallel-group, placebo-controlled study investigating the efficacy, safety and tolerability of six dosing groups of oral LOU064 in subjects with inadequately controlled CSU despite treatment with (second generation) H1-antihistamine. The study comprised of the 7 treatment arms: LOU064 10 mg q.d., LOU064 35 mg q.d., LOU064 100 mg q.d., LOU064 10 mg b.i.d, LOU064 25 mg b.i.d., LOU064 100 mg b.i.d. and placebo.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 311 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This was a global Phase 2b multicenter, randomized, double-blind, parallel-group, placebocontrolled study investigating the efficacy, safety and tolerability of 6 dosing groups of oral LOU064 in subjects with inadequately controlled CSU despite treatment with (second generation) H1-antihistamine. Study duration was 18 weeks (2 weeks of screening period; 12 weeks of treatment period and a 4 weeks follow-up period).

Study had 7 arms: 10 mg LOU064 q.d.; 35 mg LOU064 q.d.; 100 mg LOU064 q.d.; 10 mg LOU064 b.i.d.; 25 mg LOU064 b.i.d.; 100 mg LOU064 b.i.d.; and Placebo

Throughout study, subjects were treated with a 2nd generation H1-antihistamine at a locally approved licensed posology ("background medication"). Subjects could take an additional second generation H1-antihistamine that was eliminated primarily via renal excretion (e.g. cetirizine, levocetirizine or bilastine) as rescue medication. Eligible subjects could roll over to extension at Wk 12 or Wk 16

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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: LOU064 Arm 1
10 mg LOU064 qd capsule once daily
Drug: LOU064 Arm 1
10 mg LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85

Experimental: LOU064 Arm 2
35 mg capsule qd LOU064 once daily
Drug: LOU064 Arm 2
35 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85

Experimental: LOU064 Arm 3
100 mg capsule qd LOU064 once daily
Drug: LOU064 Arm 3
100 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85

Experimental: LOU064 Arm 4
10 mg capsule LOU064 bid
Drug: LOU064 Arm 4
10mg bid of LOU064 orally, twice daily from Day 1 to 85

Experimental: LOU064 Arm 5
25 mg capsule LOU064 bid
Drug: LOU064 Arm 5
25 mg bid of LOU064 orally, twice daily from Day 1 to 85

Experimental: LOU064 Arm 6
100 mg capsule LOU064 bid
Drug: LOU064 Arm 6
100 mg bid of LOU064 orally, twice daily from Day 1 to 85

Placebo Comparator: Placebo Arm
Participants took matching placebo twice daily
Drug: Placebo arm
Matching placebo, orally, twice daily from Day 1 to 85




Primary Outcome Measures :
  1. Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 [ Time Frame: Baseline, Week 4 ]

    UAS7 score change (LS mean Change) from baseline at Week 4 estimated with a mixed-effect repeated measurement analysis of UAS7 score change from baseline (FAS)

    The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (week 4 score minus Baseline score) indicates improvement.



Secondary Outcome Measures :
  1. Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 [ Time Frame: Week 12 ]
    UAS7 score change (LS mean Change) from baseline at Week 12 estimated with a mixed-effect repeated measurement analysis of UAS7 score change from baseline (FAS)

  2. Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6) [ Time Frame: Week 12 ]
    UAS7=0 and UAS7<=6 response rate over time by treatment group (non-responder imputation) The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates more severe disease. A negative change score (week 4 score minus Baseline score) indicates improvement.

  3. Cumulative Number of Weeks With an AAS7=0 Response [ Time Frame: Baseline to Week 12 ]
    The Weekly angioedema activity score (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 more severe disease.

  4. Percentage of Participants With DLQI Score of 0 or 1 [ Time Frame: Week 4 and Week 12 ]

    Percentage of subjects with DLQI 0/1 response by treatment group and visit (non-responder imputation)

    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.


  5. Mean Change From Baseline in DLQI Score [ Time Frame: Baseline, Week 4 and Week 12 ]

    Summary of DLQI score and change from baseline

    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).


  6. 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 .

  7. 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 .

  8. 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 Weeks 4 and 12



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 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

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): NCT03926611


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] January 8, 2019
Statistical Analysis Plan  [PDF] May 17, 2021

Additional Information:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03926611    
Other Study ID Numbers: CLOU064A2201
2018-000993-31 ( EudraCT Number )
First Posted: April 24, 2019    Key Record Dates
Results First Posted: February 16, 2022
Last Update Posted: April 29, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
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


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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
Urticaria Activity Score
Angioedema Activity Score
CSU
Additional relevant MeSH terms:
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Urticaria
Chronic Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases