A safety and efficacy study to find the dose of QGE031 as add-on therapy in patients with Chronic Spontaneous Urticaria (CSU)

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2014-005559-16-ES
• Date of registration: 02/06/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica, S.A.
• Public title: A safety and efficacy study to find the dose of QGE031 as add-on therapy in patients with Chronic Spontaneous Urticaria (CSU)
• Scientific title: A multicenter, randomized, double-blind, placebo and active-controlled phase 2b dose-finding study of QGE031 as add-on therapy to investigate the efficacy and safety in patients with Chronic Spontaneous Urticaria (CSU)
• Date of first enrolment: 04/08/2015
• Target sample size: 360
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005559-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 6
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Germany, Greece, Japan, Russian Federation, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Departamento Médico (ICRO)
• Affiliation: Novartis Farmacéutica, S.A.

• Name: Departamento Médico (ICRO)
• Affiliation: Novartis Farmacéutica, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
Male and female adult patients aged >/=18 to Diagnosis of CSU (with or without urticarial dermographism when testing for dermographism) refractory to H1-AH at approved or increased doses alone, or in combination with H2-AH and/or leukotriene receptor antagonist (LTRA) defined by all of the following:
The presence of itch and hives for >/= 6 consecutive weeks at any time prior to
enrollment despite current use of H1-AH (up to four times the approved dosage),
or in combination with H2-AH and/or LTRA treatment during this time period
UAS7 score (range 0-42) >/=16 and HSS7 (range 0-21) >/=8 during 7 days prior to randomization (Day 1)
In-clinic UAS >/= 4 on at least one of the screening visit days (Day -14, Day -7, or Day 1)
Patients must have been on H1-AH at approved or increased doses (up to fourfold) alone or in combination with H2-AH and/or a LTRA for treatment of CSU for at
least the 3 consecutive days immediately prior to the Day -14 screening visit and must have documented current use on the day of the initial screening visit
CSU diagnosis for >/=6 months
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 340
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lifes prior to Visit 1, whichever is longer.
History of hypersensitivity to any of the study drugs or its components, or to drugs of similar chemical classes.
Clearly defined underlying etiology for chronic urticarias other than CSU. This includes the following:
Inducible urticaria: urticaria factitia, cold-, heat-, solar-, pressure-, delayed pressure-,
aquagenic-, cholinergic-, or contact-urticaria
Diseases with possible symptoms of urticaria or angioedema such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency)
Patients with a stool examination positive for ova or parasites (at screening); re-screening may be considered if a repeat stool examination is negative following treatment.
Any other skin disease associated with chronic itching that might confound the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus etc.)
Previous exposure to omalizumab or QGE031
History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior to randomization
Inability to comply with study and follow-up procedures
Use of prohibited treatment detailed in protocol


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Spontaneous Urticaria
MedDRA version: 18.0 Level: LLT Classification code 10009159 Term: Chronic urticaria System Organ Class: 100000004858

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Code: QGE031
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Legilizumab
Current Sponsor code: QGE031
Other descriptive name: Anti-IgE antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Xolair 150 mg powder and solvent for solution for injection
Product Name: Xolair 150 mg powder and solvent for solution for injection
Product Code: IGE025
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: OMALIZUMAB
CAS Number: 242138-07-4
Current Sponsor code: IGE025
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Main Objective: To establish the dose-response relationship of QGE031 with respect to achievement of complete hives response at Week 12 in patients with CSU when added to H1-AH alone or in combination with H2-AH and/or a LTRA

Secondary Objective: Evaluate efficacy of QGE031 compared to omalizumab 300 mg with respect to achievement of complete hives response at Week 12
Evaluate the efficacy of individual QGE031 doses of 24 mg, 72 mg and 240 mg s.c. compared to omalizumab 300 mg with respect to achievement of complete hives response
at Week 20
Evaluate the efficacy of QGE031 doses of 24 mg, 72 mg and 240 mg s.c. versus placebo and omalizumab 300 mg:
Change from Baseline in Hives Severity Score (HSS7)
Change from Baseline in Itch Severity Score (ISS7)
Change from Baseline in Urticaria Activity Score (UAS7)
Evaluate the safety and tolerability of QGE031 versus placebo and omalizumab 300 mg

Primary end point(s): Achieving complete hives response at Week 12. Complete hives response is defined as a HSS7 score of 0. Analogously, complete itch
response and complete UAS7 response are defined as an ISS7 and UAS7 score of 0, respectively.

Timepoint(s) of evaluation of this end point: at Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: at Week 12 and Week 20 (as indicated in protocol)

Secondary end point(s): Evaluate the efficacy of QGE031 based on the selected dose response model compared to omalizumab 300 mg with respect to achievement of complete hives response.
Evaluate the efficacy of individual QGE031 doses of 24 mg, 72 mg and 240 mg s.c. compared to omalizumab 300 mg with respect to achievement of complete hives response
Evaluate the efficacy of QGE031 doses of 24 mg, 72 mg and 240 mg s.c. versus placebo and omalizumab 300 mg in patients with CSU, in terms of:
Change from Baseline in Hives Severity Score (HSS7)
Change from Baseline in Itch Severity Score (ISS7)
Change from Baseline in Urticaria Activity Score (UAS7)
evaluate the safety (including immunogenicity) and tolerability of QGE031 versus placebo and omalizumab 300 mg in patients with CSU particularly in regards to
ECG
adverse events
vital signs
and clinical laboratory

Secondary ID(s)

NCT01716754

CQGE031C2201

2014-005559-16-DE

Source(s) of Monetary Support

Novartis Pharma AG