E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with systemic lupus erythematosus (SLE) will be under investigation who show high disease activity despite treatment with standard immunosuppressive therapies: high-dose corticosteroids and pulse intravenous CYC at doses of 500-1000mg/m2 for at least 6 months or mycophenolate mofetil (MMF) at doses of at least 2g/d for at least 6 months. Active disease is defined according to BILAG-scoring level A. |
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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 safety and efficacy of immunoablation with antithymocyte globulin and cyclophosphamied followed by autologous hematopoietic stem cell transplantation versus treatment with currently available immunosuppressive/immunomodulatory therapy for refractory SLE |
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E.2.2 | Secondary objectives of the trial |
- To assess durability of clinical response with respect to percentage and number of subjects showing complete remission at Month 48, defined as SLEDAI less than 3 in the absence of immunosuppressive therapy and prednisolone dosage ≤ 7.5mg daily. - To assess time-point and number of patients with relapse, defined as increase in prednisolone dosage >10mg/d (for SLE treatment) or increase in SLEDAI by at least 3 compared to previous visit - To assess serological response including serum autoantibody titers and complement levels C3, C4 - To assess health related Quality of Life - To assess organ specific response parameters based on individual SLE manifestations - To assess immune reconstitution - To search for predictive factors favouring long-term remission
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of SLE according to American College of Rheumatology (ACR) classification criteria for SLE 2. Age between 18 and 60 years, inclusive 3. Provision of informed consent by subject or legally acceptable representative 4. Severe disease, refractory to standard immunosuppressive therapy defined as: - failure of remission after treatment with high-dose corticosteroids and pulse intravenous CYC at doses of 500-1000mg/m2 for at least 6 months (defined as BILAG level A) for one of the following: Biopsy proven glomerulonephritis WHO class III or class IV Parenchymal disease of heart or lung Neuropsychiatric lupus Autoimmune cytopenia OR - recurrence of disease activity (defined as new BILAG level A) within one year of clinical remission in the presence of an adequate maintenance therapy (intravenous Cyclophosphamide, Mycophenolate Mofetil, Azathioprine, Methotrexate, IVIG, Cyclosporine, Rituximab) in patients with persistent anti-dsDNA antibodies
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E.4 | Principal exclusion criteria |
1. Severe concomitant disease or organ damage a) Renal: chronic renal insufficiency with creatinine-clearance <40ml/min or serum creatinine concentration >3mg/dl b) Cardiac: congestive heart failure, LVEF < 40% determined by echocardiogram uncontrolled arrhythmia c) Pulmonary: mean PAP >50mmHg, TLCO/VA <40 % predicted d) Gastrointestinal: liver cirrhosis (Child Pugh classification B or C) 2. Concurrent malignancy or history of malignancy within 5 years of screening 3. Women who are pregnant or breastfeeding or use non-reliable methods of contraception 4. Subjects with a history of viral infection (CMV, EBV, HCV) within 6 prior to screening, or known HIV-infection 5. History of allergy to cyclophosphamide or anti-thymocyte globulin
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E.5 End points |
E.5.1 | Primary end point(s) |
SLE patients achieving complete clinical remission at Month 24 after autologous hematopoietic stem cell transplantation, defined as SLEDAI less than 3 in the absence of immunosuppressive therapy and prednisolone ≤ 5mg daily. |
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.5 | 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
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The trial will be finished with the last follow-up visit at Month 48. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
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 |