A Single-center, Double-blind Placebo-controlled Parallel Group Phase II Study of the Efficacy and Safety of Rilonacept in Subjects With Cold Contact Urticaria (CCU)
Overview
- Phase
- Phase 2
- Intervention
- Rilonacept
- Conditions
- Cold Contact Urticaria
- Sponsor
- Charite University, Berlin, Germany
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- To assess the effect of rilonacept on the clinical signs and symptoms of CCU
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
Cold contact urticaria (CCU) is a frequent form of physical urticaria that is characterized by the development of wheal and flare type skin reactions due to the release of histamine and other proinflammatory mast cell mediators following exposure of the skin to cold. Typically, symptoms occur within minutes after cold contact, including exposure to cold air, liquids or objects and are limited to cold exposed skin areas.
The investigators postulate that there is an overlap between acquired cold urticaria and cold-induced autoinflammatory syndromes, and that cold urticaria patients unresponsive to antihistamines will benefit from IL-1 targeting treatment strategies.
This study will evaluate the efficacy and safety of the IL-1 transfusion protein rilonacept in patients with cold contact urticaria who could not be successfully treated with first-line medication such as antihistamines.
This is a double-blind placebo-controlled parallel group phase II study of the efficacy and safety of rilonacept in subjects with CCU. A total of 20 patients will be included by the Urticaria specialty clinics of ACC. The total duration of the study course for each patient is 14 weeks and is divided in:
- Screening period (2 weeks, days -14-0)
- Placebo-controlled double-blind phase (Part A, 6 weeks, days 0-42)
- Open label phase (Part B, 6 weeks, days 42-84) All eligible patients will be randomized (1:1 randomization) to one of two groups: 1) Rilonacept 160mg/week or 2) Placebo, and will receive the respective dose subcutaneously. Following the placebo-controlled double-blind phase patients will enter the open-label phase and receive rilonacept open-label treatment (160mg or 320mg depending on treatment response during part A).
Investigators
Karoline Krause
PD MD
Charite University, Berlin, Germany
Eligibility Criteria
Inclusion Criteria
- •Adult ( \> 18 years of age)
- •Outpatients with CCU for more than six weeks. Urticaria symptoms must comprise wheal and itch and be resistant to conventional antihistamine treatment in standard doses
- •Patients with a positive cold stimulation test at 4°C (assessed by TEMPtest 3.0)
- •Informed consent signed and dated. Able to read, understand and willing to sign the informed consent form
- •Able to read, understand and complete study-related questionnaires
- •Willing, committed and able to return for all clinic visits and complete all study-related procedures, including willingness to self-administer SC injections or to have SC injections administered by a qualified person
- •In women, negative pregnancy test
- •Reliable method of contraception for both women of childbearing potential as well as men, during the course of the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.
- •Subjects are considered eligible according to the following tuberculosis (TB) screening criteria:
- •No history of latent or active TB prior to screening
Exclusion Criteria
- •Treatment with a live (attenuated) virus vaccine during the month prior to day 0 (Randomization).
- •A history of serious chronic or active infection(s) eg. listeriosis within six weeks prior to the screening visit.
- •Evidence of acute or latent Tuberculosis as defined by the local guidelines/local medical practice
- •A history of acute tuberculosis despite the proper treatment.
- •Significant concomitant illness such as, but not limited to, cardiac, renal, neurological, endocrinological, metabolic, lymphatic or hematological disease that would adversely affect the subject's participation or evaluation in this study.
- •Active systemic inflammatory condition including, but not limited to, rheumatoid arthritis, systemic lupus erythematosis, polymyalgia rheumatica, vasculitis, or myositis.
- •History of fibromyalgia or chronic fatigue syndrome.
- •Evidence of current HIV, Hepatitis B, or Hepatitis C infection by clinical or serological history.
- •History of malignancies including malignant hematological disorders other than a successfully treated non-metastatic cutaneous, basal, or squamous cell carcinoma and/or in situ cervical cancer within five years of the Screening visit.
- •Severe respiratory disease, including, but not limited to severe bronchiectasis, chronic obstructive pulmonary disease, bullous lung disease, uncontrolled asthma, or pulmonary fibrosis.
Arms & Interventions
Placebo
Placebo s.c every 7 days
Intervention: Rilonacept
Rilonacept 160mg
Rilonacept s.c every 7 days
Intervention: Placebo
Outcomes
Primary Outcomes
To assess the effect of rilonacept on the clinical signs and symptoms of CCU
Time Frame: 6 weeks
Change in symptom development (critical temperature thresholds (CTT) in CCU patients from baseline to day 42 in the rilonacept group as compared to the placebo group
Secondary Outcomes
- To assess the safety of rilonacept in subjects with CCU(6 weeks)