A Phase III Study of and Efficacy of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines.
- Conditions
- Chronic Spontaneous Urticaria
- Interventions
- Registration Number
- NCT03580356
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this study was to establish efficacy and safety of ligelizumab in adolescent and adult subjects with CSU who remained symptomatic despite standard of care treatment by demonstrating better efficacy over omalizumab and over placebo.
The study population consisted of 1,079 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1078
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ligelizumab 120 mg Ligelizumab Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w Omalizumab 300 mg Omalizumab Omalizumab 300 mg arm: 2 injections of 1.2 mL omalizumab q4w Placebo 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 Ligelizumab 72 mg Ligelizumab Ligelizumab 72 mg arm: 1 injection of 0.6 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS) 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
Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects 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
Name Time Method Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS) 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.
Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS) 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.
Number and Percentage of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) 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. Data is presented as percentage of patients with a UAS7=0 score. No Statistical analysis was planned for adolescent group.
Number and Percentage of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents) Week 12 Assessed as percentage of subjects achieving DLQI = 0-1, which means 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). Data is presented as percentage of patients with a DLQI=0 score. No statistical analysis was planned for adolescent group.
Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS) 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.
Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS) 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.
Trial Locations
- Locations (35)
Allervie Clinical Research
🇺🇸Birmingham, Alabama, United States
Medical Resch of Arizona-Div of Allergy Asthma and Immunology
🇺🇸Scottsdale, Arizona, United States
Atria Clinical Research Asthma and Allergy Institute
🇺🇸Little Rock, Arkansas, United States
DeMera Allergy Asthma and Immun Ctr
🇺🇸Fresno, California, United States
California Allergy and Asthma Medical Group
🇺🇸Los Angeles, California, United States
Jonathan Corren Inc
🇺🇸Los Angeles, California, United States
Allergy and Asthma Consultants
🇺🇸Redwood City, California, United States
Allergy and Asthma Associates of Santa Clara Vally Center
🇺🇸San Jose, California, United States
Sarasota Clinical Research
🇺🇸Sarasota, Florida, United States
Olympian Clinical Research
🇺🇸Tampa, Florida, United States
Idaho Research
🇺🇸Eagle, Idaho, United States
Midwest Allergy Sinus Asthma SC
🇺🇸Normal, Illinois, United States
John Hopkins University
🇺🇸Baltimore, Maryland, United States
Institute for Asthma and Allergy PC
🇺🇸Chevy Chase, Maryland, United States
Chesapeake Clinical Research
🇺🇸White Marsh, Maryland, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Midwest Clinical Research LcLC
🇺🇸Saint Louis, Missouri, United States
Montana Medical Research
🇺🇸Missoula, Montana, United States
The Asthma and Allergy Center PC
🇺🇸Papillion, Nebraska, United States
Icahn School Of Med At Mount Sinai
🇺🇸New York, New York, United States
Toledo Institute of Clinical Research
🇺🇸Toledo, Ohio, United States
Allergy Asthma and Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
PCR DBA Columbia Asthma and Allergy
🇺🇸Clackamas, Oregon, United States
Allergy and Asthma Specialists PC
🇺🇸Blue Bell, Pennsylvania, United States
Allergy and Clinical Immunology Associates
🇺🇸Pittsburgh, Pennsylvania, United States
National Allergy and Asthma Research LLS
🇺🇸North Charleston, South Carolina, United States
Bellaire Dermatology Associates
🇺🇸Bellaire, Texas, United States
Western Sky Medical Research
🇺🇸El Paso, Texas, United States
North Texas Inst For Clinical Tri
🇺🇸Fort Worth, Texas, United States
Allergy and Asthma Research Center PA
🇺🇸San Antonio, Texas, United States
Quality Assurance Research Center
🇺🇸San Antonio, Texas, United States
Allergy and Asthma Care of Waco
🇺🇸Waco, Texas, United States
Allergy Associates of Utah
🇺🇸Sandy, Utah, United States
Bellingham Asthma Allergy and Immunology
🇺🇸Bellingham, Washington, United States
Novartis Investigative Site
🇻🇳Ho Chi Minh, Vietnam