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A Phase III Study of Safety and Efficacy of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With 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: NCT03580369
Recruitment Status : Completed
First Posted : July 9, 2018
Results First Posted : December 30, 2022
Last Update Posted : December 30, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

The purpose of this study was to establish safety and efficacy of ligelizumab in adolescent and adult subjects with Chronic Spontaneous Urticaria (CSU) who remain symptomatic despite standard of care treatment by demonstrating better efficacy over omalizumab and over placebo.

The study population consisted of 1,072 male and female subjects aged ≥ 12 years who were diagnosed with CSU and who remained symptomatic despite the use of H1-antihistamines.

This was a multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group study. There was a screening period of up to 28 days, a 52 week double-blind treatment period, and a 12 week post-treatment follow-up period.


Condition or disease Intervention/treatment Phase
Chronic Spontaneous Urticaria Biological: Ligelizumab Biological: Omalizumab Other: Placebo Phase 3

Detailed Description:

This was a Phase III multi-center, randomized, double-blind, active and placebo-controlled, parallel-group study. The study consisted of 3 distinct periods:

  • Screening period (Day -28 to Day 1): Duration of up to 4 weeks in which subjects who have given informed consent were assessed for eligibility.
  • Double-blind treatment period (52 weeks): The subjects were seen in the clinic every 4 weeks.
  • Post-treatment follow-up period (12 weeks): This period consists of 3 visits (every 4 weeks) with the final visit occurring 16 weeks after the last dose at Week 48.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1072 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This was a Phase III multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group study. There was a screening period of up to 28 days, a 52 week double-blind treatment period, and a 12 week post-treatment follow-up period.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Patients, investigator staff and personnel performing the study assessments remained blinded to the identity of the treatment from the time of randomization until final database lock. The study drug was prepared by an independent unblinded pharmacist (or authorized delegate) and administered by an independent unblinded study drug administrator. Neither the unblinded pharmacist nor the unblinded study drug administrator was involved in any assessments.
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Active and Placebo-controlled Study to Investigate the Safety and Efficacy of Ligelizumab (QGE031) in the Treatment of Chronic Spontaneous Urticaria (CSU) in Adolescents and Adults Inadequately Controlled With H1-antihistamines
Actual Study Start Date : October 17, 2018
Actual Primary Completion Date : July 16, 2021
Actual Study Completion Date : June 14, 2022


Arm Intervention/treatment
Experimental: Ligelizumab 120 mg
Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w
Biological: Ligelizumab
Liquid in vial

Experimental: Ligelizumab 72 mg
Ligelizumab 72 mg arm: 1 injection of 0.6 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w
Biological: Ligelizumab
Liquid in vial

Active Comparator: Omalizumab 300 mg
Omalizumab 300 mg arm: 2 injections of 1.2 mL omalizumab q4w
Biological: Omalizumab
Lyophilized powder for solution in vial

Placebo Comparator: Placebo
Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48
Other: Placebo
Liquid in vial




Primary Outcome Measures :
  1. Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects [ Time Frame: Baseline, Week 12 ]

    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.

    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).

    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


  2. Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS) [ Time Frame: Baseline, Week 12 ]

    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.

    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).

    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



Secondary Outcome Measures :
  1. Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) [ Time Frame: Week 12 ]

    The Urticaria Activity Score (UAS) is the sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete UAS7 response is defined as UAS7 = 0.

    No Statistical analysis was planned for adolescent group.


  2. Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS) [ Time Frame: Baseline, Week 12 ]

    Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12

    Itch Severity Score (ISS) is on a scale of 0 to 3. 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 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.


  3. Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS) [ Time Frame: Baseline, Week 12 ]

    Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12

    Itch Severity Score (ISS) is on a scale of 0 to 3. 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 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.. No Statistical Analysis was planned for adolescent population.


  4. Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) [ Time Frame: Baseline, Week 12 ]

    Assessed as percentage of subjects achieving DLQI = 0-1, meaning, no impact on subjects quality of life at Week 12

    The Dermatology life Quality Index (DLQI) 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).

    No statistical anaylsis was planned for adolescent group.


  5. Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS) [ Time Frame: Baseline, Week 12 ]

    Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12

    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 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.


  6. Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS) [ Time Frame: Baseline, Week 12 ]

    Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12

    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 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.

    No Statistical Analysis was planned.




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.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Signed informed consent must be obtained prior to participation in the study. The subject's, parent's or legal guardian's signed written informed consent and child's assent, if appropriate, must be obtained before any assessment is performed. Of note, if the subject reaches age of consent (age as per local law) during the study, they will also need to sign the corresponding study Informed Consent Form (ICF) at the next study visit.
  • Male and female subjects ≥ 12 years of age at the time of screening.
  • CSU diagnosis for ≥ 6 months.
  • Diagnosis of CSU refractory to H1-AH at approved doses at the time of randomization, as defined by all of the following:
  • The presence of itch and hives for ≥ 6 consecutive weeks at any time prior to Visit 1 (Day - 28 to Day -14) despite current use of non-sedating H1-antihistamine
  • UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during the 7 days prior to randomization (Visit 110, Day 1)
  • Subjects must be on H1-antihistamine at only locally label approved doses for treatment of CSU starting at Visit 1 (Day -28 to Day -14)
  • Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules.

Key Exclusion Criteria:

  • History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes (i.e. to murine, chimeric or human antibodies).
  • Subjects having a clearly defined cause of their chronic urticaria, other than CSU. This includes, but is not limited to, the following: symptomatic dermographism (urticaria factitia), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic- or contact-urticaria.
  • Diseases, other than chronic urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency).
  • Subjects with evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines. All subjects will be screened at Visit 1. If stool testing is positive for pathogenic organism, the subject will not be randomized and will not be allowed to rescreen.
  • Any other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).
  • Prior exposure to ligelizumab or omalizumab.
  • H1-AH used as background medication at greater than locally label-approved doses after visit 1

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): NCT03580369


Locations
Show Show 161 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] January 7, 2021
Statistical Analysis Plan  [PDF] July 1, 2022

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03580369    
Other Study ID Numbers: CQGE031C2302
2018-000839-28 ( EudraCT Number )
First Posted: July 9, 2018    Key Record Dates
Results First Posted: December 30, 2022
Last Update Posted: December 30, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

URL: https://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 ):
Anti-IgE
CSU
chronic spontaneous urticaria
hives severity score
itch severity score
urticaria activity score
Additional relevant MeSH terms:
Layout table for MeSH terms
Urticaria
Chronic Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Chronic Disease
Disease Attributes
Pathologic Processes
Omalizumab
Anti-Allergic Agents
Anti-Asthmatic Agents
Respiratory System Agents