Dupilumab in Chronic Spontaneous Urticaria

Chronic Spontaneous Urticaria Clinical Trial

— DUPICSU  

Official title:

A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-concept Phase 2, 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 Chronic Spontaneous Urticaria Despite H1-antihistamine Treatment.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03749135
• Other study ID #: D-001-01
• Secondary ID: 2017-004458-41
• Status: Completed
• Phase: Phase 2
• Start date: November 12, 2018
• Est. completion date: July 7, 2021

Study information

• Verified date: February 2022
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy in reducing disease activity and safety of Dupilumab in adult patients with chronic spontaneous urticaria (CSU) who are symptomatic despite H1-antihistamine treatment.

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 CSU 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 CSU. 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 CSU consists of administration of antihistamines. In more than 50% of the patients, symptoms persist with standard dosing of antihistamines. In antihistamine-refractory patients with chronic spontaneous urticaria, the currently only licensed treatment is omalizumab, a monoclonal anti-IgE antibody. In 2014, omalizumab has been licensed for add-on therapy in CSU patients who still have symptoms despite standard-dosed antihistamine treatment. There is, however, still a great medical need for additional treatment options, as 20-40% of patients are still without effective therapy. These patients have no other licensed treatment option and can only be treated off-label with therapeutics with several known safety risks such as Cyclosporine A. Dupilumab has excellent potential to provide symptom control in CSU. 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 CSU symptoms.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: July 7, 2021
• Est. primary completion date: July 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Diagnosis: chronic spontaneous urticaria (defined as 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 moderate to severe CSU and refractory to standard of care

treatment at the time of randomization, as defined by the following:

1. The presence of itch and hives for more than 6 consecutive weeks at any time prior to enrollment despite current use of H1 antihistamine

2. Urticaria activity score UAS7 score (range 0-42) equal or more than 16, 7 days prior to randomization (Day 1)

3. CSU 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. Patients whose urticaria is solely due to inducible urticaria.

2. Other diseases with symptoms of urticaria or angioedema, including urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency)

3. 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.)

4. 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 drug

5. History of anaphylactic shock

6. Active helminthic parasite infection or treatment of helminthic parasites within 6 months of screening

Related Conditions & MeSH terms

• Angioedema
• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Recurrent Angioedema
• Urticaria

Intervention

Drug:
• Dupilumab
anti-IL4-Receptor alpha
• Placebo
Placebo

Locations

Country	Name	City	State
Germany	Charite University, Berlin, Germany	Berlin
Germany	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen
Germany	Universitätsmedizin Leipzig, Klinik für Dermatologie, Venerologie und Allergologie	Leipzig	Sachsen
Germany	Hautklinik der Universitätsmedizin Mainz Clinical Research Center	Mainz	Rheinland-Pfalz, Germany
Germany	Universitätsklinikum Giessen und Marburg	Marburg	Hessen
Germany	Hautklinik Universitätsklinikum Münster	Münster	NRW, Germany

Sponsors (3)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Proinnovera GmbH, Sanofi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urticaria activity score over 7 days (UAS7)	0-42 Points total range over 7 days, higher values equal more disease activity	Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)
Secondary	Itch severity score (ISS7; 0 - no pruritus; 21 - most severe pruritus), hive severity score (HSS7; 0 - no hives; 21 - max. hive severity)	Disease activity scores	Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)
Secondary	Global assessment for disease activity	Global assessment for disease activity(physician and patient) by visual analogue scale (VAS; 0 - no pain; 10 - max. amount of pain)	Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)
Secondary	urticaria control test (UCT; 16 - complete disease control; 0 - strong symptoms), dermatological quality of life (DLQI; 0 - no impairment; 30 - max. impairment), chronic urticaria quality of life (Cu2-QoL; 23 - no impairment; 115 - max. impairment)	Disease specific quality of life	Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)
Secondary	Responder rates (regarding disease activity and quality of live (QoL))	Responder rates (regarding disease activity and quality of live (QoL))	Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)
Secondary	rate of angioedema burdened days angioedema activity score (AAS; 0 - lowest disease activity; 15 - highest disease activity) angioedema quality of life (AE-Qol; 0 - no impairment; 100 - worst impairment)	For patients with concomitant angioedema	Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]
Secondary	Rescue medication use	Frequency of of how often rescue medication is used	Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]