Chronic Spontaneous Urticaria (CSU)

The purpose of this extension study is to collect long-term efficacy, safety and tolerability data on remibrutinib in a selected group of participants with Chronic Spontaneous Urticaria (CSU) who previously completed the treatment phase of remibrutinib preceding Phase 3 studies.

Remibrutinib (LOU064)

Remibrutinib (LOU064)

Film coated tablet

25

Efficacy:
Absolute change from baseline in UAS7 at Week 12

1. Signed informed consent must be obtained prior to participation in the study
2. Male and female adult participants ≥18 years of age at the time of screening
3. CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined
by the investigator based on all available supporting documentation)
4. Diagnosis of CSU inadequately controlled by second generation H1-antihistamines at the
time of randomization defined as:
 The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite
the use of second generation H1-antihistamines during this time period
 UAS7 score (range 0-42) ≥ 16, ISS7 score (range 0-21) ≥ 6 and HSS7 score (range 0-
21) ≥ 6 during the 7 days prior to randomization (Day 1)
5. Documentation of hives within three months before randomization (either at screening
and/or at randomization; or documented in the participants`s medical history)
6. Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of
the study and adhere to the study protocol
1. Signed informed consent must be obtained prior to participation in the study
2. Male and female adult participants ≥18 years of age at the time of screening
3. CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined
by the investigator based on all available supporting documentation)
4. Diagnosis of CSU inadequately controlled by second generation H1-antihistamines at the
time of randomization defined as:
 The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite
the use of second generation H1-antihistamines during this time period
 UAS7 score (range 0-42) ≥ 16, ISS7 score (range 0-21) ≥ 6 and HSS7 score (range 0-
21) ≥ 6 during the 7 days prior to randomization (Day 1)
5. Documentation of hives within three months before randomization (either at screening
and/or at randomization; or documented in the participants`s medical history)
6. Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of
the study and adhere to the study protocol

1. Use of other investigational drugs within 5 half-lives, or within 30 days (for small
molecules) prior to Screening or until the expected pharmacodynamic (PD) effect has
returned to baseline (for biologics), whichever is longer; or longer if required by local
regulations
2. Previous use of remibrutinib or other BTK inhibitors
3. History of hypersensitivity to any of the study treatments or its excipients or to drugs of
similar chemical classes
4. Participants having a clearly defined predominant or sole trigger of their chronic urticaria
(chronic inducible urticaria) including urticaria factitia (symptomatic dermographism),
cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contacturticaria
5. Other diseases with symptoms of urticaria or angioedema, including but not limited to
urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary
urticaria, or drug-induced urticaria
6. Any other skin disease associated with chronic itching that might influence in the
investigator’s opinion the study evaluations and results, e.g. atopic dermatitis, bullous
pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis
7. Participants taking medications prohibited by the protocol (see Table 6-3)
8. Known history or evidence of ongoing alcohol or drug abuse within the last 6 months
before randomization
9. History of malignancy of any organ system (other than localized basal cell carcinoma of
the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless
of whether there is evidence of local recurrence or metastases
10. Pregnant or nursing (lactating) women
11. Women of child-bearing potential (WoCBP), defined as all women physiologically
capable of becoming pregnant, unless they are using highly effective methods of
contraception during dosing and for 7 days after stopping of study treatment. Highly
effective contraception methods include:
 Total abstinence (when this is in line with the preferred and usual lifestyle of the
participant). Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) total hysterectomy or bilateral tubal ligation at least six weeks before
taking investigational drug. In case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow up hormone level
assessment
 Male sterilization (at least 6 months prior to screening). For female participants on the
study, the vasectomized male partner should be the sole partner for that participant
 Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of
contraception or other forms of hormonal contraception that have comparable efficacy
(failure rate < 1%), for example hormone vaginal ring or transdermal hormone
contraception or placement of an intrauterine device (IUD) or intrauterine system
(IUS)
In case of use of oral contraception women should have been stable on the same pill for a
minimum of 3 months before taking investigational drug.
Women are considered post-menopausal if they have had 12 months of natural
(spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate,
history of vasomotor symptoms). Women are considered not of child bearing potential if
they are post-menopausal or have had surgical bilateral oophorectomy (with or without
hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of
oophorectomy alone, only when the reproductive status of the woman has been confirmed
by follow-up hormone level assessment is she considered not of child bearing potential.
If local regulations deviate from the contraception methods listed above to prevent
pregnancy, local regulations apply and will be described in the informed consent form
(ICF).
12. Major surgery within 8 weeks prior to screening or planned surgery for the duration of the
study
13. History of live attenuated vaccine within 6 weeks prior to randomization or requirement to
receive these vaccinations at any time during study drug treatment
14. Evidence of clinically significant cardiovascular (such as but not limited to myocardial
infarction, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure,
arrhythmia and uncontrolled hypertension within 12 months prior to Visit 1), neurological,
psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders,
gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would
compromise the safety of the participant, interfere with the interpretation of the study
results or otherwise preclude participation or protocol adherence of the participant
15. Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares
are commonly treated with oral or parenteral corticosteroids
16. Hematology parameters at screening:
 Hemoglobin: < 10 g/dl
 Platelets: < 100 000/mm3
 Leucocytes: < 3 000/mm3
 Neutrophils: < 1 500/mm3
17. Significant bleeding risk or coagulation disorders
18. History of gastrointestinal bleeding, e.g. in association with use of nonsteroidal antiinflammatory drugs (NSAID), that was clinically relevant (e.g. requiring hospitalization or
blood transfusion)
19. Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or
clopidogrel. The use of dual anti-platelet therapy (e.g. acetylsalicylic acid + clopidogrel) is
prohibited.
20. Requirement for anticoagulant medication (for example, warfarin or Novel Oral AntiCoagulants (NOAC))
21. History or current hepatic disease including but not limited to acute or chronic hepatitis,
cirrhosis or hepatic failure or Aspartate Aminotransferase (AST)/ Alanine
Aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or
International Normalized Ratio (INR) of more than 1.5 at screening
22. History of renal disease, creatinine level above 1.5x ULN, or estimated Glomerular
Filtration Rate (eGFR) < 45ml/min (using the Cockcroft-Gault equation) at screening
23. Evidence of an ongoing Hepatitis C infection (e.g. defined by the detection of hepatitis C
virus ribonucleric acid (HCV-RNA) at screening) and/or an ongoing Hepatitis B infection
(defined by the detection of hepatitis B virus surface antigen (HBsAg) and/or hepatitis B
virus (HBV)-DNA at screening; participants who are positive for anti-hepatitis B core
(HBc) antibodies but who are negative for antibodies against HBsAg and HBV-DNA can
be included into the study if they agree to monitoring for HBsAg and HBV-DNA reactivation)
24. Known or suspected ongoing, chronic or recurrent infectious disease including but not
limited to opportunistic infections (e.g. tuberculosis, atypical mycobacterioses, listeriosis
or aspergillosis) and/or known positivity for Human Immunodeficiency Virus (HIV)
infection. HIV antigen/antibody tests will be performed to determine HIV status if
required according to local regulations