The purpose of this study is to establish efficacy and safety of ligelizumab (QGE031) versus placebo in participants with chronic inducible urticaria who remain symptomatic despite treatment with H1 antihistamine.
ID
Source
Brief title
Condition
- Angioedema and urticaria
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To demonstrate superiority of ligelizumab versus placebo with regards to the
change from baseline in response to a standardized provocation test for each
CINDU subtype.
Secondary outcome
To demonstrate superiority of ligelizumab versus placebo with regard to
proportion of participants with a complete response after standardized
provocation test
To demonstrate superiority of ligelizumab versus placebo in itch NRS following
the provocation test.
To assess the safety of ligelizumab
Background summary
Patient with chronic urticaria suffer from itchy hives, with symptoms that are
difficult to treat and last for more than 6 weeks. Urticaria can occur
spontaneously (chronic spontaneous urticaria (CSU)), or be triggered by
external stimuli (chronic inducible urticaria (abbreviated CINDU)).
The standard treatment for CINDU is an H1 antihistamine. Approximately half of
the patients do not benefit sufficiently from this treatment, not even in
higher doses. There is therefore a need for better treatments.
QGE031 is a so-called monoclonal antibody, a drug that was specially developed
in the laboratory to counteract the production of a body substance
(immunoglobulin E or IgE). IgE plays a role in allergic reactions. QGE031 is
similar to the medicine Xolair (omalizumab), which is registered in the
Netherlands for the treatment of CSU. Laboratory tests showed that QGE031 was
better at inhibiting the production of IgE and better at countering allergic
skin reactions than omalizumab.
Study objective
The purpose of this study is to establish efficacy and safety of ligelizumab
(QGE031) versus placebo in participants with chronic inducible urticaria who
remain symptomatic despite treatment with H1 antihistamine.
Study design
This is a Phase III multi-center, randomized, double-blind, active and
placebo-controlled, parallel study. There is a screening period of up to 28
days, a double-blind 12-week treatment period followed by a 12-week treatment
period in which everyone receives QGE031. Finally, there is a 12-week follow-up
period after treatment.
Intervention
* Ligelizumab 120 mg sc q4w
* Ligelizumab 72 mg sc q4w
* Placebo 0 mg sc q4w
Study burden and risks
Burden:
- 6 s.c. injections every 4 weeks
- Physical examination 1x
- Measurement of height and weight : 4x
- Blood test : 11x sampling 5-35 ml each time
- Urine examination : 4x
- Pregnancy test for female subjects: 12x
- Fecal analysis 2x of 3 fecal samples
- Keep a diary (daily), during the whole study
- ECG: 2x
There is a possibility that side effects may occur from the study medication or
from the study tests. At this time, not all possible side effects of the study
medication are known.
Possible side effects of ligelizumab
- Very common side effects (in about 1 person in 10) are reactions at the
injection site: redness, pain, itching, swelling, bruising, heat, infiltrate
(hard swelling) and/or oedema (fluid).
- Common side effects (in about 1 person in 100) are urticaria (hives) and
generalized itching.
- Rare side effects (in about 1 person in 10,000) are angioedema and
Anaphylactic reaction.
naphylaxis:
There is a possibility that your child/ward may experience a severe allergic
reaction or anaphylaxis (which can be a life-threatening condition) after
receiving study medication.
Your study doctor will monitor you closely for symptoms of an allergic reaction
while you are receiving study treatment at the study site and, in particular,
for a period of time after your injections. Your study doctor should talk to
you about seeking urgent medical assistance if you have symptoms of an allergic
reaction after leaving the study site.
Signs and symptoms of a severe allergic reaction are:
* Wheezing, shortness of breath, chest tightness or trouble breathing
* Low blood pressure, dizziness, fainting, rapid or weak heartbeat, anxiety,
flushing, feeling warm or the feeling that something bad is about to happen
(impending doom)
* Swelling of the throat or tongue, throat tightness, hoarse voice, or trouble
swallowing
Parasitic Infections:
There is a possibility that you may experience diarrhea or other symptoms that
could be from a parasitic infection. This could occur at any time between
visits before end of study. If that happens, please inform your study doctor,
since additional stool sampling to check for parasitic infections has to be
collected as soon as possible.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
1. Signed informed consent must be obtained before any assessment is performed.
2. Participant's parent's or legal guardian's signed informed consent and
child's assent, if appropriate, must be obtained before any assessment is
performed.
3. Male and female participants * 12 years of age at the time of screening.
4. Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism,
cold urticaria or cholinergic urticaria for * 4 months (defined as onset of
CINDU with supporting documentation (e.g medical record, clinical history,
photographs)).
5. Diagnosis of CINDU (symptomatic dermographism, cold urticaria or cholinergic
urticaria) inadequately controlled with H1-AH at local label approved doses at
the time of randomization.
6. Participants must be able to physically perform the protocol defined
provocation test specific to the participant's CINDU.
7. Cholinergic urticaria participants must show sweating in performing the
pulse-controlled ergometry test on day of randomization. Participants with
anhidrosis must not be included.
8. Willing and able to complete a daily symptom eDiary as per protocol
requirement and adhere to the study visit schedules.
Exclusion criteria
1. Use of other investigational drugs within 5 half-lives of enrollment, or
within 30 days for small molecules prior to the screening visit or until the
expected pharmacodynamic effect has returned to baseline for biologics,
whichever is longer.
2. History of hypersensitivity to any of the study drugs or its components or
to drugs of similar classes (i.e. to murine, chimeric or human antibodies) or
to the provocation test or items used in provocation tests.
3. Participants who have any concomitant CSU at screening.
4. Participants who have a familial form (e.g familial cold autoinflammatory
syndrome, familial cold urticaria) of the target CINDU that is being considered
for the participant's inclusion in this study.
5. Participants having a more defined other form of inducible urticaria than
the target CINDU that is being considered for the participant's inclusion in
this study.
6. Diseases, other than chronic inducible 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).
7. Any other skin disease associated with chronic itching that might influence,
in the investigator's opinion, the study evaluations and results (eg, atopic
dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus,
etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic
dermographism.
8. Prior exposure to ligelizumab, omalizumab or other anti-IgE therapies.
9. Female participants, including adolescent females of 12 to less than 18
years of age, of child-bearing potential, defined as all women physiologically
capable of becoming pregnant, unless they are using effective methods of
contraception during dosing of study treatment.
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 | EUCTR2020-003018-11-NL |
| ClinicalTrials.gov | NCT05024058 |
| CCMO | NL77053.100.21 |