| Eligibility |
Inclusion Criteria:
Diagnosis: cholinergic urticaria (ongoing disease)
1. Patient is informed about study procedures and medications and has given written
informed consent before any assessment.
2. Patient is able to communicate with the investigator, understands and complies with
the requirements of the study.
3. Male or Female
4. Patient is 18-75 years of age
5. Patient is diagnosed with CholU and refractory to standard of care treatment at the
time of randomization, as defined by the following:
The presence of itch and hives for equal or more than 6 consecutive weeks at any time
prior to enrollment despite current use of licensed dose H1 antihistamine Urticaria
control test UCT less than 12 prior to randomization (Day 1) CholU diagnosis for 6
months
6. Willing and able to complete a daily symptom diary for the duration of the study and
adhere to the study visit schedules.
7. Patients must not have more than one missing diary entry in the 7 days prior to
randomization. Re-screening may be considered.
8. Women of childbearing potential have to agree to use an acceptable form of
contraception (as determined by the site investigator) and have to continue its use
for the duration of the study.
Exclusion Criteria:
1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5
half-lives of enrollment, whichever is longer; or longer if required by local
regulations, and for any other limitation of participation in an investigational trial
based on local regulations.
2. History of hypersensitivity to any of the study drugs (Dupilumab, rescue medication)
or their components or to drugs of similar chemical classes.
3. Clearly dominating other form of urticaria as etiology for wheal and flare type
reactions. This includes the following: Chronic spontaneous urticaria, inducible
urticaria: urticaria factitia, cold-, heat-, solar-, pressure-, delayed pressure-,
aquagenic, or contact-urticaria. These diseases are allowed as comorbidities, if
cholinergic urticaria is the dominating form of chronic urticaria.
4. Other diseases with symptoms of urticaria or angioedema, including urticaria
vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and
hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency)
5. Any other active skin disease associated with chronic itching that might confound the
study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis
herpetiformis, etc.)
6. Patients who have received concomitant prohibited medication within the last 3 months
prior to screening:
- Anti-IgE therapy (e.g. omalizumab)
- Routine (daily or every other day during 5 or more consecutive days) doses of
systemic corticosteroids or other immunosuppressants
- Intravenous immunoglobulins
- Biological therapy
- Systemic immunosuppressants
- Live/attenuated vaccines
- Other investigational drugs
7. Use of prohibited treatment detailed in protocol (see section 6.5.8 and Table 3:
Prohibited treatment).
8. History of anaphylactic shock.
9. Presence of hypereosinophilic diseases (blood eosinophils >1500 cells/mm3 at the
latest available test).
10. Presence of clinically significant cardiovascular, bronchial, neurological,
psychiatric, metabolic or other pathological conditions that could interfere with the
interpretation of the study results and/or compromise the safety of the patients.
11. Medical examination or laboratory findings that suggest the possibility of
decompensation of co-existing conditions for the duration of the study. Any items that
are cause for uncertainty must be reviewed with the Medical Monitor.
12. Inability to comply with study and follow-up procedures.
13. History of malignancy of any organ system (other than localized basal cell carcinoma
or actinic keratosis or Bowen disease: carcinoma in situ of skin; carcinoma in situ of
the cervix or non-invasive malignant colon polyps that have been removed), treated or
untreated, within the past 5 years, regardless of whether there is evidence of local
recurrence or metastases.
14. Evidence of severe renal dysfunction at screening
15. Patient considered potentially unreliable or where it is envisaged the patient may not
consistently attend scheduled study visits.
16. Serious psychiatric and/or psychological disturbances.
17. History or evidence of ongoing drug or alcohol abuse, within the last 6 months prior
to randomization.
18. Patient unable to complete a patient diary or complete questionnaires on paper.
19. Any other condition or prior/current treatment, which in the opinion of the
investigator renders the patient ineligible for the study schedule.
20. Study personnel or first degree relatives of investigator(s) must not be included in
the study.
21. Subjects who live in detention on court order or on regulatory action as per local and
national law (see ยง40 subsection 1 sentence 3 no. 4 Arzneimittelgesetz)
22. Pregnant or nursing (lactating) women, where pregnancy is defined
23. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive human chorionic gonadotropi (hCG) laboratory test.
24. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, UNLESS they are using highly-effective methods of contraception
during the duration of the study. Highly-effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of
the patient), 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) or tubal ligation at least six weeks before taking study treatment.
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 m prior to screening). For female patients on the
study, the vasectomized male partner should be the sole partner for that patient.
- Use of oral, 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
- 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 study treatment.
Note: Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical
profile (e.g. age appropriate, history of vasomotor symptoms) or six months of
spontaneous amenorrhea with serum (follicle-stimulating hormone) FSH levels > 40
(milli international units) mIU/mL; or have had surgical bilateral oophorectomy (with
or without hysterectomy) at least six months 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.
25. Patients with active confirmed SARS -CoV2 infection are to be excluded
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