E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mixed cryoglobulinemia (type II or III) associated with chronic HCV infection (positive serology and/or HCV viremia) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011474 |
E.1.2 | Term | Cryoglobulinaemia |
|
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 efficacy of rituximab at the reduced dosage of 250 mg/m2 x 2 for the treatment of HCV-associated MC |
|
E.2.2 | Secondary objectives of the trial |
Correlation of B-cell depletion with clinical efficacy. Decrease of the requency of circulating B-cells with t(14;18)Bcl-2/IgH. Decrease of the frequency of monoclonal circulating B-cells. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A diagnosis of mixed cryoglobulinemia (type II or III) associated with chronic HCV infection (positive serology and/or HCV viremia). At least one of the following signs and symptoms of cryoglobulinemic vasculitis: - purpura - skin ulcer(s) - peripheral neuropathy (documented by ENG) - renal involvement (creatinine >2 mg/dl and increased BUN, and/or proteinuria >500 mg/day) - gastrointestinal involvement (vasculitis of the esophagus, stomach, small intestine, colon, or any intraabdominal viscera presenting as unexplained abdominal pain, gastrointestinal hemorrhage or intestinal ischemia) - signs & symptoms of hyperviscosity. - pulmonary involvement (pulmonary hemorrage caused by vasculitis) - severe CNS involvement (signs of active CNS vasculitis at MRI) Previous failure of anti-HCV therapy (PEG-IFN and ribavirine), relapse after response without indication to retreatment (according to the AIFA guidelines), contraindication or intolerance to anti-HCV therapy. |
|
E.4 | Principal exclusion criteria |
Previous treatment with rituximab Coexistence of life-threatening condition(s) unrelated to MC. A diagnosis of hematological or non-hematological malignancy. HIV or HBV positive Ongoing therapy with high dose corticosteroids and/or immunosuppressive drugs Ongoing plasmapheresis course (eligible 2 months after interruption) Any ongoing infection |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Response rate at 12 weeks (BVAS < 50% baseline; cryocrit <50% baseline) Remission at 6 and 12 months (BVAS=0; cryocrit <20% baseline) Time to remission relapses during a 1-year follow up |
|
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 | Yes |
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 | No |
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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |