Cholinergic Urticaria - Efficacy of Dupilumab

NCT03749148 | Completed Phase 2

• 2 other identifiers: D-001-022017-001262-25
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 8

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).

Conditions

Cholinergic Urticaria

Keywords

hives; itch; exercise

Outcome Measures

Primary Outcomes (1)

• cholinergic Urticaria activity score over 7 days (CholUAS7)

  0-42 points total range, 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 Outcomes (6)

• Global assessment

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

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

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

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

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

• Responder rates and sypmtom patterns

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

• Urticaria control test, dermatological quality of life, cholinergic urticaria quality of life

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

Study Arms (2)

Dupilumab

ACTIVE COMPARATOR

Dupilumab, s.c. administration 2 injections (600mg) as loading dose, 1 injection (300mg) every 14 days for a total of 16 weeks

Drug: Dupilumab

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Dupilumab DRUG

anti-IL4-Receptor alpha

Dupilumab

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Sanofi: collaborator
• Proinnovera GmbH: collaborator

Study Sites (8)

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Universitätsklinikum Giessen und Marburg

Marburg, Hesse, 35043, Germany

Location

Uniklinik RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Hautklinik Universitätsklinikum Münster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Hautklinik der Universitätsmedizin Mainz Clinical Research Center

Mainz, Rhineland-Palatinate, 55101, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, 01307, Germany

Location

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

Kiel, Schleswig-Holstein, Germany

Location

Charité-Universitätsmedizin Berlin

Berlin, 12203, Germany

Location

MeSH Terms

Conditions

Urticaria; Pruritus; Motor Activity

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• Marcus Maurer, Prof.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: randomized, double blind, placebo controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Phase 2 multicenter, randomized, double blind, placebo controlled, proof of concept, parallel group, two-arm, investigator-initiated trial (IIT)

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: November 21, 2018
• Study Start: December 10, 2018
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: September 6, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8)