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Cholinergic UrticariaPhase 2CHEDNCT03749148

Cholinergic Urticaria - Efficacy of Dupilumab

A Phase 2 study testing Dupilumab in people with Cholinergic Urticaria, run by Charite University, Berlin, Germany at 8 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Cholinergic Urticaria
What is being tested?
Dupilumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
48 participants
Where
8 sitesGermany
Study dates
10 Dec 2018to 28 Feb 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis: cholinergic urticaria (ongoing disease)
  • Patient is informed about study procedures and medications and has given written informed consent before any assessment.
  • Patient is able to communicate with the investigator, understands and complies with the requirements of the study.
  • Male or Female
  • Patient is 18-75 years of age
  • Patient is diagnosed with CholU and refractory to standard of care treatment at the time of randomization, as defined by the following:
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  • 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
  • Willing and able to complete a daily symptom diary for the duration of the study and adhere to the study visit schedules.
  • Patients must not have more than one missing diary entry in the 7 days prior to randomization. Re-screening may be considered.
  • 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.

Who cannot join

  • 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.
  • History of hypersensitivity to any of the study drugs (Dupilumab, rescue medication) or their components or to drugs of similar chemical classes.
  • 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.
  • 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)
  • 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.)
  • Patients who have received concomitant prohibited medication within the last 3 months prior to screening:
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  • 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
  • Use of prohibited treatment detailed in protocol (see section 6.5.8 and Table 3: Prohibited treatment).
  • History of anaphylactic shock.
  • Presence of hypereosinophilic diseases (blood eosinophils >1500 cells/mm3 at the latest available test).
  • 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.
  • 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.
  • Inability to comply with study and follow-up procedures.
  • 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.
  • Evidence of severe renal dysfunction at screening
  • Patient considered potentially unreliable or where it is envisaged the patient may not consistently attend scheduled study visits.
  • Serious psychiatric and/or psychological disturbances.
  • History or evidence of ongoing drug or alcohol abuse, within the last 6 months prior to randomization.
  • Patient unable to complete a patient diary or complete questionnaires on paper.
  • Any other condition or prior/current treatment, which in the opinion of the investigator renders the patient ineligible for the study schedule.
  • Study personnel or first degree relatives of investigator(s) must not be included in the study.
  • 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)
  • Pregnant or nursing (lactating) women, where pregnancy is defined
  • 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.
  • 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.
  • Patients with active confirmed SARS -CoV2 infection are to be excluded

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Germany8 sites

  • Uniklinik RWTH Aachen

    Aachen, North Rhine-Westphalia, 52074

  • Charité-Universitätsmedizin Berlin

    Berlin, 12203

  • Universitätsklinikum Carl Gustav Carus

    Dresden, Saxony, 01307

  • Universitätsklinikum Erlangen

    Erlangen, Bavaria, 91054

  • Universitätsklinikum Schleswig-Holstein, Klinik für Dermatologie, Venerologie und Allergologie

    Kiel, Schleswig-Holstein

  • Hautklinik der Universitätsmedizin Mainz Clinical Research Center

    Mainz, Rhineland-Palatinate, 55101

  • Universitätsklinikum Giessen und Marburg

    Marburg, Hesse, 35043

  • Hautklinik Universitätsklinikum Münster

    Münster, North Rhine-Westphalia, 48149

Other trials in Germany

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Proof of Concept, 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

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).

Read the 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 European Medicines Agency (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 immunoglobulin E (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 chronic spontaneous urticaria (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.

Being tested
Dupilumab, Placebo
Keywords
hives, itch, exercise
Medical subject headings
Urticaria, Pruritus, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DupilumabDrug

    anti-IL4-Receptor alpha

  • PlaceboDrug

    Placebo

Study groups in NCT03749148
Study groupRoleWhat they receive
DupilumabActive comparatorDupilumab, s.c. administration 2 injections (600mg) as loading dose, 1 injection (300mg) every 14 days for a total of 16 weeks
Receives: Drug: Dupilumab
PlaceboPlacebo comparatormatching Placebo, s.c. administration 2 injections as loading dose, 1 injection every 14 days for a total of 16 weeks
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. cholinergic Urticaria activity score over 7 days (CholUAS7)

    0-42 points total range, higher values equal more disease activity

    Measured: Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)]

Secondary outcomes (6)

  1. Global assessment

    Global assessment (physician and patient) by visual analogue score (VAS; 0 - no pain; 10 - max. amount of pain) for disease activity

    Measured: Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)]

  2. provocation urticaria activity score (pUAS; 0 - no activity; 3 - high activity)

    Reduction in provocation urticaria activity score

    Measured: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]

  3. weekly pruritus score (PS7; 0 - no activity; 21 - high activity)

    Reduction in weekly pruritus score (PS7)

    Measured: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]

  4. Responder rates and sypmtom patterns

    symptoms assessed by diary

    Measured: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]

  5. Urticaria control test, dermatological quality of life, cholinergic urticaria quality of life

    Quality of life instruments as assessed by urticaria control test (UCT; 16 - complete disease control; 0 - max. amount of physical symptoms), dermatological quality of life (DLQI; 0 - no impairment of life quality, 30 - maximum impairment) , and cholinergic urticaria quality of life (CholUQoL; 0 - no impairment; 120 - worst impairment)

    Measured: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]

  6. Use of rescue medication

    frequency of how often rescue medication was used

    Measured: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2018
  2. Study start10 Dec 2018
  3. Primary completion28 Feb 2023
  4. Study completion28 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Phase 2 multicenter, randomized, double blind, placebo controlled, proof of concept, parallel group, two-arm, investigator-initiated trial (IIT)
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03749148
Sponsor's protocol ID
D-001-02
Other IDs
2017-001262-25, 2017
Acronym
CHED
Status last verified
Sep 2023
First submitted
12 Jul 2018
Last updated
6 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dupilumab in people with Cholinergic Urticaria, run by Charite University, Berlin, Germany at 8 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

cholinergic Urticaria activity score over 7 days (CholUAS7) (time frame: Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)]). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03749148.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2023.

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