| Eligibility |
Inclusion Criteria:
Patients eligible for inclusion in this Treatment Plan have to meet all of the following
criteria:
1. Adult male and female subjects (= 18 years) who are able and willing to provide
written informed consent prior to enrolling in the cohort.
2. CSU diagnosis for = 6 months (defined as onset of CSU with supporting documentation).
3. Diagnosis of CSU refractory to H1-AH at locally label approved doses and to omalizumab
(where applicable), as assessed by the treating physician, using one of the following
tools: UAS7, UCT or DLQI
4. Not eligible or able to enroll in a clinical trial or no relevant clinical trials
available
Exclusion Criteria:
Patients eligible for this Treatment Plan must not meet any of the following criteria:
1. Previous premature discontinuation from a remibrutinib clinical trial for any reason
2. History of hypersensitivity to remibrutinib or its excipients or to other BTK
inhibitors
3. 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 contact-urticaria
4. 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
5. Any other skin disease associated with chronic itching that might influence in the
physician's opinion the treatment effect, e.g. atopic dermatitis, bullous pemphigoid,
dermatitis herpetiformis, senile pruritus or psoriasis
6. Use of prohibited concomitant treatment
7. Known history or evidence of ongoing alcohol or drug abuse within the last 6 months
before treatment start
8. 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
9. Pregnant or nursing (lactating) women
10. 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 program 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,
post-ovulation 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 in the program, 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 bilateral 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.
11. History of live attenuated vaccine within 6 weeks prior to treatment start or
requirement to receive these vaccinations at any time during treatment with
remibrutinib
12. 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 physician's opinion, would compromise the safety of the participant, or
otherwise preclude adherence to the treatment plan
13. Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where
flares are commonly treated with oral or parenteral corticosteroids
14. Hematology parameters before treatment start:
- Hemoglobin: < 10 g/dl
- Platelets: < 100 000/mm3
- Leucocytes: < 3 000/mm3
- Neutrophils: < 1 500/mm3
15. Significant bleeding risk or coagulation disorders
16. History of gastrointestinal bleeding, e.g. in association with use of nonsteroidal
anti-inflammatory drugs (NSAID), that was clinically relevant (e.g. requiring
hospitalization or blood transfusion)
17. 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.
18. Requirement for anticoagulant medication (for example, warfarin or Novel Oral
Anti-Coagulants (NOAC))
19. 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 before treatment start
20. History of renal disease, creatinine level above 1.5x ULN, or estimated Glomerular
Filtration Rate (eGFR) <45ml/min (using the Cockcroft-Gault equation) before treatment
start
21. Evidence of an ongoing Hepatitis C infection (e.g. defined by the detection of
hepatitis C-ribonucleic 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-hepatits B core (HBc) antibodies but who are negative for antibodies against
HBsAg and HBV-DNA can be included into the program if they agree to monitoring for
HBsAg and HBV-DNA re-activation)
22. 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.
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