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Cholinergic Urticaria - Efficacy of Dupilumab (CHED)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03749148
Recruitment Status : Recruiting
First Posted : November 21, 2018
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Marcus Maurer, Charite University, Berlin, Germany

Brief Summary:
The purpose of this study is to assess the efficacy in reducing disease activity and safety of Dupilumab in adult patients with cholinergic urticarial (CholU) who are symptomatic despite H1-antihistamine treatment (licensed dose).

Condition or disease Intervention/treatment Phase
Cholinergic Urticaria Drug: Dupilumab Drug: Placebo Phase 2

Detailed Description:

Treatment with Dupilumab has been shown to reduce clinically significant exacerbations and to improve skin symptom control as well as quality of life in moderate to severe atopic dermatitis patients and in moderate to severe asthma patients. It has been approval by EMA for the treatment of atopic dermatitis patients in September 2017.

Dupilumab is a novel monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in atopic dermatitis and asthma. Considering that CholU and atopic diseases share many common features (e.g. key pathogenic role of mast cells and IgE, itch is a dominant symptom, Th2 dominance), it is reasonable to expect that Dupilumab is beneficial in CholU.

These results suggest that Dupilumab may provide an effective treatment option for patients with insufficient treatment responses to H1-antihistamines exhibiting wheal and flare type skin reactions.

The gold standard treatment of CholU consists of administration of antihistamines. In most patients, symptoms persist with standard dosing of antihistamines. In antihistamine-refractory patients with cholinergic urticaria, no other licensed treatment is currently available. In 2014, omalizumab has been licensed for add-on therapy in CSU patients who still have symptoms despite standard-dosed antihistamine treatment, but not for chronic inducible forms of urticaria. Accordingly, there is still a great medical need for additional treatment options of CholU patients that are refractory to antihistamine treatment.

Dupilumab has excellent potential to provide symptom control in CholU. This study will provide additional valuable insights into the therapeutic potential of Dupilumab in improving quality of life in these patients, in addition to managing CholU symptoms.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase 2 multicenter, randomized, double blind, placebo controlled, parallel group, two-arm, investigator-initiated trial (IIT)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: randomized, double blind, placebo controlled
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Multicenter, 16-week Treatment Study With a 16 Week Follow-up Period to Assess the Efficacy and Safety of Dupilumab (Anti-IL4Ra) in Adult Patients With Cholinergic Urticaria Despite H1-antihistamine Treatment
Actual Study Start Date : December 10, 2018
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hives
Drug Information available for: Dupilumab

Arm Intervention/treatment
Active Comparator: Dupilumab
Dupilumab, s.c. administration 2 injections (600mg) as loading dose, 1 injection (300mg) every 14 days for a total of 16 weeks
Drug: Dupilumab
anti-IL4-Receptor alpha

Placebo Comparator: Placebo
matching Placebo, s.c. administration 2 injections as loading dose, 1 injection every 14 days for a total of 16 weeks
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. cholinergic Urticaria activity score over 7 days (CholUAS7) [ Time Frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)] ]
    0-42 points total range, higher values equal more disease activity



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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 §40 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 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 FSH levels > 40 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03749148


Contacts
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Contact: Sabine Altrichter, MD +49-30-450618368 sabine.altrichter@charite.de
Contact: Karen Ottenstein +49-30-450 618435 karen.ottenstein@charite.de

Locations
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Germany
Hautklinik Universitätsklinikum Münster Recruiting
Münster, Nordrhein-Westfalen, Germany, 48149
Contact: Randolf Brehler       randolf.brehler@ukmuenster.de   
Contact: Gesine Dannlowski    02518356506    Gesine.dannlowski@ukmuenster.de   
Hautklinik der Universitätsmedizin Mainz Clinical Research Center Recruiting
Mainz, Rheinland-Pfalz, Germany, 55101
Contact: Petra Staubach-Renz, Dr. med.    +49 (0)6131 175732    petra.staubach@unimedizin-mainz.de   
Contact: Gabriele Hagedorn    +49 (0) 6131 172944    gabriele.hagedorn@unimedizin-mainz.de   
Sub-Investigator: Anna Sohn, Dr. med.         
Charité-Universitätsmedizin Berlin Recruiting
Berlin, Germany, 10117
Contact: Sabine Altrichter, Dr. med.         
Contact: Karen Ottenstein, Dr.    +49 30 450 618 435    karen.ottenstein@charite.de   
Sponsors and Collaborators
Charite University, Berlin, Germany
Sanofi
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Responsible Party: Marcus Maurer, Principal Investigator, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT03749148    
Other Study ID Numbers: D-001-02
First Posted: November 21, 2018    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Marcus Maurer, Charite University, Berlin, Germany:
hives
itch
exercise
Additional relevant MeSH terms:
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Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases