E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048820 |
E.1.2 | Term | Urticarial vasculitis |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of a single dose of Ilaris® on the clinical signs and symptoms of urticarial vasculitis (UV) |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety, tolerability and immunogenicity following administration of ACZ885 to patients with active UV
To assess the effect of Ilaris® on the systemic manifestations of UV (including arthralgias and arthritis, pulmonary, gastrointestinal and renal involvement, cardiac, ocular, neurologic and general symptoms such as fever and hepatosplenomegaly)
To assess the effect of Ilaris® on laboratory parameters such as inflammation markers, complement levels, circulating immune complexes and autoantibodies
To assess the effect of Ilaris® on the patient’s quality of life
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adults (18 years or older) • UV diagnosis based on diagnostic criteria defined in Appendix 2 • Active UV, refractory to treatment with antihistamines, NSAIDS or colchicine, hydroxychloroquine or dapsone. • If necessary, concurrent/ongoing treatment with a stable dose of systemic corticosteroids not greater than 10mg/d for 14 days prior to screening • If necessary, concurrent/ongoing treatment with a stable dose of antihistamines and NSAIDs for 7 days prior to screening • Able to read, understand and willing to sign the informed consent form and abide with study procedures • Willing, committed and able to return for all clinic visits and complete all study-related procedures, including willingness to have SC injections administered by a qualified person • In females of childbearing potential: Negative pregnancy test; males and females willing to use highly effective contraception (Pearl-Index < 1). A woman will be considered not of childbearing potential if she is post-menopausal for greater than two years or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) • In men: Willingness to utilize highly effective contraception and to not have their partner become pregnant during the full course of the study. Adequate contraceptive measures include oral contraceptives (stable use for two or more cycles prior to screening); bilateral tubal ligation; vasectomy; condom or diaphragm plus either contraceptive sponge, foam or jelly • Subjects are considered eligible, if they meet 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, and negative QuantiFERON-TB test at screening (if QuantiFERON-TB test is positive, the patient can only be included if active TB is ruled out with appropriate measurements according to standard of care). • No participation in other clinical trials 4 weeks before and after participation in this study
|
|
E.4 | Principal exclusion criteria |
• Concurrent/ongoing treatment with Anakinra (Kineret®) or recent treatment within 3 days prior to screening • Concurrent/ongoing treatment with other biologics or recent treatment (less than 5 half lives) • with oral Corticosteriods greater than 10 mg/d within 2 weeks prior to screening • with parenteral Corticosteriods within 4 weeks prior to screening • with Cyclosporin A Methotrexate, Dapsone, Chloroquine, Hydroxychloroquine, Azathioprine, Cyclophosphamide within 4 weeks prior to screening • other immunosuppressives within 4 weeks or 5 half lives prior to screening, whichever is longer • Evidence of recurrent or latent systemic infection such as tuberculosis • Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial • Treatment with a live (attenuated) virus vaccine during three months prior to Baseline visit (Visit 2) • 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 prior to screening • Significant concomitant illness such as, but not limited to, cardiac, renal, neurological, endocrinological, metabolic, or lymphatic disease that would adversely affect the subject’s participation or evaluation in this study • Active systemic inflammatory condition other than UV including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus or Sjögren’s Syndrome • 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 within five years prior to screening other than a successfully treated non-metastatic cutaneous, basal, or squamous cell carcinoma and/or in situ cervical cancer • History of a demyelinating disease or multiple sclerosis • Severe respiratory disease, including, but not limited to severe bronchiectasis, chronic obstructive pulmonary disease, bullous lung disease, uncontrolled asthma, or pulmonary fibrosis • Presence of any of the following laboratory abnormalities at enrollment visit: creatinine >1.5 x Upper Limit of Normal (ULN), WBC <3000/µl; platelet count <100000/µl ; ALT or AST >3.0 x ULN • Lactating females or pregnant females • Males not willing to use highly effective contraception • Enrollment in another investigational treatment or device study or use of an investigational agent, or 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 • Any medical condition which, in the opinion of the Investigator, would interfere with participation in the study or place the subject at risk • 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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in the mean UV activity score (UVAS) from the last 2 weeks of the baseline phase (day -14 to day 0) to the last 2 weeks of the first 4 weeks treatment phase (day 15 to 28) of the study (The UVAS combines the key symptoms of UV). Daily UVAS values will be documented using DHAFs (Daily Health Assessment Forms). Values for the Sum UVAS can range from 0 to 50 per day (5 symptoms, 0-10 each). Mean Daily UVAS will be calculated by dividing the sum of the daily activity scores by 5. |
|
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 | No |
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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |