E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
cold contact urticaria (CCU) |
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E.1.1.1 | Medical condition in easily understood language |
urticaria symptoms after exposure to low temperatures |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of rilonacept on the clinical signs and symptoms of cold contact urticaria |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of rilonacept in subjects with cold contact urticaria
To assess changes in patients’ quality of life during the treatment period with rilonacept
To assess the effects of rilonacept on mast cell mediator release in blood of cold contact urticaria patients during the challenge with cold water bath provocation with defined temperatures.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult 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 All subjects will have received a normal Chest radiograph (CXR) within 6 months prior to enrollment (signing of consent) which notes the absence of calcified granulomas and/or pleural scarring consistent with tuberculosis. Subjects are considered eligible according to the following tuberculosis (TB) screening criteria: - No history of latent or active TB prior to screening - No signs or symptoms suggestive of active TB - No recent close contacts with a person with active TB - A negative QuantiFERON-TB test on day -14 (screening visit).
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E.4 | Principal exclusion criteria |
Treatment with a live (attenuated) virus vaccine during three months prior to day 0 (Randomization) An abnormal chest radiograph consistent with clinical signs of prior or present tuberculosis infection whether or not previously treated with anti-tuberculosis agents A history of listeriosis, active tuberculosis, persistent chronic or active infection(s) requiring treatment with parenteral antibiotics, parenteral antivirals, or parenteral antifungals within four weeks, or oral antibiotics, oral antivirals, or oral antifungals within two weeks prior to the Screening visit Significant concomitant illness such as, but not limited to, cardiac, respiratory, renal, neurological, endocrinological, metabolic, lymphatic or hematological disease that would adversely affect the subject’s participation or evaluation in this study 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 Presence of any of the following laboratory abnormalities at enrollment visit: creatinine >1.5 x Upper Limit of Normal (ULN), WBC <3.6 x 103/mm3; platelet count <150,000 mm3; ALT or AST >2.0 x ULN Previous ineffective treatment with an IL1 inhibitor or other biologic agent Known hypersensitivity to CHO cell derived therapeutics or proteins or any components of rilonacept Any medical condition which, in the opinion of the Investigator, would interfere with participation in the study or place the subject at risk Present History of substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) that could limit the subject’s ability to comply with study procedures Lactating females or pregnant females Enrollment in another investigational treatment or device study or use of an investigational agent, or no completion of less than 4 weeks or 5 half-lives, whichever is longer, since end of another investigational device or drug trial Subjects for whom there is concern about compliance with the protocol procedures Subjects who are detained officially or legally to an official institute
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in symptom development (critical temperature thresholds (CTT) in CCU patients challenged with defined temperatures using TEMPtest® 3.0 after treatment with rilonacept 160mg and 320mg as compared to placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change in critical stimulation time threseholds (CSTT) in CCU patients challenged with 40C using TEMPtest® 3.0 for defined time periods after treatment with rilonacept 160mg and 320mg as compared to placebo Safety of patients treated with rilonacept 160mg and 320mg: This includes physical examination, routine safety laboratory assessments, vital signs and adverse event reporting Change in the patient’s quality of life, as assessed by the Dermatology Life Quality Index (DLQI) during the treatment period Change in the investigator’s assessment of total disease activity (visual analogue scale, ACUSI, see apendix) from the screening phase to the double-blind and open-label treatment phase Mast cell mediator release in blood of CCU patients during the challenge with cold water after the treatment with riolonacept 160mg and 320mg as compared to placebo.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |