E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 |
continue to assess the safety of epratuzumab dosed at 1200mg bi-weekly for a total of two doses in 12-week re-treatment cycles in moderate to severe systemic lupus patients. |
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E.2.2 | Secondary objectives of the trial |
- continue to assess the tolerability of epratuzumab. - continue to assess the efficacy of epratuzumab. - continue to assess the kinetics and attributes of B and T cells in circulation. - continue to assess the pharmacokinetics, pharmacodynamics and immunogenicity of epratuzumab. - continue to assess the health-related quality of life benefits of epratuzumab treatment. - continue to assess the utility benefits of epratuzumab treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. SL0007 patients completing week 12 and patients early terminating at study week 8 (Visit 8) or later due to treatment failure as described in the SL0007 protocol. 2. Patients who completed study SL0007 must have maintained eligibility requirements (including concomitant medication restrictions) throughout their participation in the SL0007 study. Patients who terminated study SL0007 early due to use of restricted concomitant Lupus medications (e.g. increased corticosteroid dose) resulting in treatment failure may be eligible to enter SL0008. These patients should be discussed with the medical monitor on a case by case basis. 3. Written informed consent signed prior to the initiation of any study-specific assessments at Visit 1 (patients who will be participating in SL0008 must sign informed consent for study SL0008 prior to receiving any assessments for the last visit of SL0007 as data from this visit will be used for both studies). |
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E.4 | Principal exclusion criteria |
1. Active, severe neuropsychiatric SLE including but not limited to BILAG A criteria as follows: existing aseptic meningitis, cerebral vasculitis, demyelination syndromes (including ascending or transverse myelitis and acute inflammatory demyelinating polyradiculoneuropathy), myelopathy, acute confusional state, impaired level of consciousness, psychosis, cranial neuropathy, plexopathy, grand mal seizure, status epilepticus, cerebellar ataxia, stroke or stroke syndrome, chorea or any other severe neurologic condition which, in the opinion of the investigator, would prevent the subject from completing protocol required procedures. Mononeuritis multiplex is NOT excluded provided it is not new (within the past 4 weeks). 2. Active severe SLE disease activity which involves the Renal system (defined by BILAG renal level A activity or Grade III or higher WHO nephritis) or serum creatinine >2.5mg/dL or clinically significant (per investigator judgment) serum creatinine increase within the 4 weeks prior to Visit 1 or proteinuria > 3.5gm/day. 3. Female subjects who are pregnant or lactating. Women of childbearing potential are required to have a negative pregnancy test at Visit 1 prior to the first dose of study medication. A urine pregnancy test will be completed every 4 weeks for the duration of the trial and must be negative in order for the subject to continue in the trial. Women of childbearing potential must use an acceptable method of birth control during the study and for a period of 3 months after the last dose of study medication (oral contraceptives must be stable for at least one full month prior to Visit 1). Abstinence is not an acceptable method of contraception for the study. Use of barrier contraception is only acceptable for use in this trial if a double barrier method is used. (e.g., spermacide with condom, or diaphragm with spermacide). Females not receiving birth control must be surgically sterile, postmenopausal for at least 2 years prior to Visit 1, or must have undergone tubal ligation. 4. Evidence of an immunosuppressive state including HIV infection, agammaglobulinemias, T-cell deficiencies or HTLV-1 infection at any time prior to or during the study. 5. Patients with a history of chronic infections including, but not limited to hepatitis B or C. Patients with a history of a recent, serious or life-threatening infection (e.g. pneumonia or herpes zoster) or any current sign or symptoms that may indicate a significant infection at Visit 1 as per the Investigator’s clinical judgment. Patients must have completed any antibiotics prior to the first dose of study medication. 6. Patients who in the opinion of the investigator are at a particularly increased risk of developing a serious infection due to their lifestyle, occupational or social contacts. 7. Substance abuse/dependence or other concurrent medical conditions that could confound study interpretation or affect the patient’s ability to tolerate or complete the study. 8. Patients may not receive any live (or live attenuated) vaccines during the course of the study. 9. Use of oral anticoagulants or anti-platelet treatment regardless of indication or route (not including NSAIDS) within the 4 weeks prior to Visit 1. 10. Patients with a history of anti-phospholipid antibody syndrome. 11. Significant hematologic abnormalities not attributed to Lupus including iron-deficiency anemia, hemoglobin < 8.0 g/dL, WBC < 2000/mm³, absolute neutrophil count < 1500/mm³, platelets < 50,000/mm³. 12. History of malignant cancer, except the following treated cancers: cervical CIS, basal cell carcinoma or squamous cell carcinoma. 13. Use of the following medications in Table 5:1, (page 39 of protocol) regardless of route, during the SL0007 study or while enrolled in SL0008. Use of exclusionary medication during the trial will result in the patient being discontinued from trial participation.
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E.5 End points |
E.5.1 | Primary end point(s) |
Number and percent of patients with BILAG improvement defined as BILAG A’s at study baseline (SL0007 Visit 1) improved to B/C/D and BILAG B’s at study baseline (SL0007 Visit 1) improved to C/D and no BILAG. Worsening in other BILAG organ systems such that there are no new BILAG A’s or two new BILAG B’s as compared to Visit 1 of SL0007. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 12-week treatment cycle. |
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E.5.2 | Secondary end point(s) |
1. The combined response index analysis evaluating BILAG, SLEDAI, and a physician's global assessment and treatment failure status [ Time Frame: Every 4 weeks through week 48, then every 12 weeks through completion] 2. The combined response index including an additional criteria involving the SF-36 response [ Time Frame: Every 12 weeks ] 3. BILAG score assessment [ Time Frame: Every 4 weeks through week 48, then every 12 weeks through completion ] 4. SLEDAI scores assessment [ Time Frame: Every 4 weeks through week 48, then every 12 weeks through completion ] 5. Patient and physician VAS [ Time Frame: Every 4 weeks through week 48, then every 12 weeks through completion ] 6. Percentage of patients achieving SF-36 stabilization or improvement as compared to baseline [ Time Frame: Every 12 weeks ] 7. SF-36 PCS, MCS [ Time Frame: Every 12 weeks ] 8. EQ-5D results [ Time Frame: Every 12 weeks ] 9. Proportion of patients meeting treatment failure [ Time Frame: Every 12 weeks ] 10. Total daily steroid dose [ Time Frame: Every 4 weeks for the first 48 weeks and then every 12 weeks ] 11. Time to flare for patients who entered the study without flare as defined by the BILAG [ Time Frame: over the entire course of the trial ] 12. SLEDAI responder [ Time Frame: Every 4 weeks for the first 48 weeks and then every 12 weeks ] 13. Time to sustained response for patients entering SL0008 with flare as defined by the BILAG. [ Time Frame: over the entire course of the trial ] 14. Immunogenicity as measured by human anti-human antibodies [ Time Frame: at each dosing visit and 4 weeks post first dose of each treatment cycle ] 15. Assessment of changes in baseline in levels of circulating B and T cells [ Time Frame: The first dosing visit of each treatment cycle and at 4 weeks post first dose of each treatment cycle ]
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Every 4 weeks through week 48, then every 12 weeks through completion 2. Every 12 weeks 3. Every 4 weeks through week 48, then every 12 weeks through completion 4. Every 4 weeks through week 48, then every 12 weeks through completion 5. Every 4 weeks through week 48, then every 12 weeks through completion 6. Every 12 weeks 7. Every 12 weeks 8. Every 12 weeks 9. Every 12 weeks 10. Every 4 weeks for the first 48 weeks and then every 12 weeks 11. over the entire course of the trial 12. Every 4 weeks for the first 48 weeks and then every 12 weeks 13. over the entire course of the trial 14. at each dosing visit and 4 weeks post first dose of each treatment cycle 15. The first dosing visit of each treatment cycle and at 4 weeks post first dose of each treatment cycle
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Brazil |
Hong Kong |
Hungary |
India |
Lithuania |
Poland |
Spain |
Ukraine |
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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
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Last visit of the last subject. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |