The purpose of this study is to establish efficacy and safety of ligelizumab in adolescent and adult subjects with CSU who remain symptomatic despite standard of care treatment by demonstrating better efficacy over omalizumab.
ID
Source
Brief title
Condition
- Angioedema and urticaria
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the study is to demonstrate that ligelizumab (72 mg
q4w and/or 120 mg q4w) is superior to placebo and superior to omalizumab 300 mg
q4w in change from baseline in UAS7 at Week 12
Secondary outcome
Objective 1: To demonstrate that a greater proportion of subjects achieve UAS7
= 0 at Week 12 who are treated with ligelizumab 72 mg q4w and/or 120 mg q4w
compared to placebotreated subjects and compared with omalizumab 300 mg q4w
treated subjects.
Objective 2: To demonstrate the superiority of ligelizumab 72 mg q4w and/or 120
mg q4w treated subjects with respect to a reduction from baseline in the weekly
itch severity score at Week 12 compared to placebo-treated subjects and
omalizumab 300 mg q4w treated subjects.
Background summary
QGE031 is a so-called monoclonal antibody, a drug that has been developed
especially in the laboratory to inhibit the production of immunoglobulin E or
IgE. IgE plays a role in allergic reactions. QGE031 resembles the drug Xolair
(omalizumab), which is registered in the Netherlands for the treatment of
asthma. Preclinical research showed QGE031 a more effective inhibitor than
omalizumab which resulted in less allergic skin reactions. Through this study,
the efficacy and safety of 52 weeks of treatment administered subcutaneously
QGE031 (every 4 weeks) in patients with CSU is assessed.
Study objective
The purpose of this study is to establish efficacy and safety of ligelizumab in
adolescent and adult subjects with CSU who remain symptomatic despite standard
of care treatment by demonstrating better efficacy over omalizumab.
Study design
This is a Phase III multi-center, randomized, double-blind, active- and
placebo-controlled, parallel-group study. There is a screening period of up to
28 days, a 52 week double-blind treatment period, and a 12 week post-treatment
follow-up period.
Intervention
* Ligelizumab 120 mg sc q4w
* Ligelizumab 72 mg sc q4w
* Omalizumab 300 mg sc q4w
* Placebo 0 mg sc q4w
Study burden and risks
Burden:
- 26 s.c. injections every 4 weeks
- Physical examination 19x
- With length and weight: 4x
- Blood test: 19x decrease 5-30 ml each time
- Optional PK / PD blood test: 6x (max 10ml each time)
- Urine research: 4x
- For female subjects pregnancy test: 17x
- Examination test 1x of 3 stool samples
- Keeping daily diary twice a day, during the entire study
- ECG: 3x
Risks:
Adverse Events QGE031 and risks/burden studyprocedures
Known Adverse events QGE031:
- Most common reported: Hives, approx. 2 hrs post injection. Disappeared
quickly after treatment of this allergic reaction.
- Allergic reactions (e.g., rash, swelling of throat and/or tongue) and some
which on rare occasion may be severe (e.g., very low blood pressure and
difficulty with breathing). The risk for a severe allergic reaction caused by
the study drug is not known yet, however there have been no occurrences so far
and the risk is considered low.
- Risks at s.c. injection site: Pain, swelling, redness and bruising.
Possible side effects of omalizumab
• Very common side effects (in 1 in 10 people or more) are side effects at the
site of the injection: redness, pain, itching, swelling, bruise, bleeding and /
or hives. Headache.
• Typical side effects (in 1 in 10 to 100 people) are hives and inflammation of
the nose and throat, sinus and upper respiratory tract.
• Rare side effects (in 1 in 1,000 to 10,000 people) are signs of a severe
allergic reaction and angioedema
Increased susceptibility to parasitic infections.
Risks/burden studyprocedures:
- Venapuncture (blood collection): Fainting, pain and/or bruising. Rarely,
there may be a small blood clot or infection at the site of the needle
puncture.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
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., * Male and female subjects >= 12 years of age at the time of
screening.
* CSU diagnosis for >= 6 months (defined as onset of CSU with supporting
documentation).
* Diagnosis of CSU refractory to H1-AH at locally label 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.
* Other protocol-defined inclusion criteria may apply
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-, cholinergicor 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, omalizumab and other IgE therapies.
* Any H2 antihistamine, LTRA (montelukast or zafirlukast) or H1-AH used as
background medication at greater than local label approved doses after Visit 1.
* Other protocol-defined exclusion criteria may apply
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-000840-24-NL |
| ClinicalTrials.gov | NCT03580356 |
| CCMO | NL66602.078.18 |