E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
systemic lupus erythematosus |
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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 | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
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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 |
assess the dose response and the dose frequency of epratuzumab during one 12-week treatment cycle in moderate to severe systemic lupus patients with active disease. |
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E.2.2 | Secondary objectives of the trial |
- assess the safety of epratuzumab - optimize knowledge about efficacy assessments to be carried to phase III confirmatory trials - assess the kinetics and attributes of B and T cells in circulation - assess the pharmacokinetics and pharmacodynamics of epratuzumab over a dose range including exposure response modeling and immunogenicity assessments - explore candidate biomarkers and gene expression relative to risk, prognosis, and response to epratuzumab treatment - assess the health-related quality of life benefits of epratuzumab treatment - explore the utility benefits of epratuzumab treatment |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Gene Expression Profiling (described in section 11 of the SL0007 protocol) objectives: - Identification of early stratification markers for drug response (efficacy, safety) - Identification of markers for disease activity - Identification of markers for efficacy - Identification of markers for safety - Understanding the molecular mechanism of action of Epratuzumab |
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E.3 | Principal inclusion criteria |
1. Male or female patients aged equal to or greater than 18 years of age at Visit 1 (screening). 2. Signed written informed consent prior to the initiation of any study-specific assessment at Visit 1 (screening). 3. Adequate reading and writing abilities (in their native language) such that the patient can comprehend and answer the questions on the patient completed assessments. 4. Positive ANA result at Visit 1 (screening) either via screening or confirmatory central laboratory testing methodologies. 5. Current diagnosis of systemic lupus erythematosus (SLE) by American College of Rheumatology revised criteria such that at least 4 (not including Neurologic Disorder) of the 11 criteria are met. If positive for Neurologic Disorder criteria, a total of 5 of the 11 ACR criteria must be met. 6. Active moderate or severe SLE disease activity as demonstrated by BILAG A level disease activity in at least one body/organ system (except renal or neurological) or BILAG B level disease activity in at least two body/organ systems if no BILAG A level disease is present. At least one of the BILAG A scores OR at least two of the BILAG B scores must be in the following categories: Mucocutaneous, Musculoskeletal or Cardiovascular/ Respiratory. 7. Active moderate or severe SLE disease activity as demonstrated by SLEDAI total score of at least 6 at Visit 1 (screening). 8. If on antimalarials, must have been receiving antimalarials for at least 12 weeks, with a stable dose regimen for at least 28 days (-1 day) prior to Visit 2 and first study medication infusion and must be maintained at the same stable dose for the entire study. 9. If on immunosuppressives, must be on a stable dose for 28 days (-1 day) prior to Visit 2 and first study medication infusion and must be maintained at the same stable dose for the entire study. Maximum allowed doses for commonly prescribed immunosuppressives are listed in Table 10:1 of the protocol. Immunosuppressant must not include any immunosuppressants specifically mentioned in the exclusion medication table. 10. Receiving corticosteroids within the range of 5 to 60 mg/day prednisone (or equivalent) at a stable dose for at least five days (-1 day) prior to Visit 2 and the first study drug infusion, with the corticosteroid dose dependent on the investigator’s assessment of disease severity. If steroids are initiated or increased for current disease flare, this increase must not have occurred more than 14 days (-1 day) prior to Visit 2 and the first infusion of study medication. Use of IV (including high pulse doses of IV Solu-Medrol), IM or IA injections of corticosteroids are not allowed at any time during the trial. |
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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 28 days (-1 day) prior to Visit 1 (screening) or proteinuria > 3.5gm/day. 3. Female subjects who are pregnant or lactating. Women of childbearing potential are required to have a serum pregnancy test taken at Visit 1 which is confirmed to be negative prior to the first dose of study medication at Visit 2. Additionally, a urine pregnancy test will be completed prior to all remaining doses and must be negative in order for the subject to receive the study drug. Urine pregnancy tests will then be repeated every four weeks and at the Follow up Visit. Women of childbearing potential must use an acceptable method of birth control during the trial and for a period of 3 months after the last dose of study medication. Acceptable forms of birth control include oral contraceptives [which must be stable for at least one full month prior to Visit 1 (screening), and should remain stable during the study], double barrier methods including diaphragm or condom with spermacide. Unacceptable methods include single barrier methods and abstinence alone. Women not receiving birth control must be surgically sterile (hysterectomy/oophrectomy or tubal ligation) or postmenopausal for at least 2 years prior to (Visit 1) screening. 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 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 (screening) 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 principal investigator are at a particularly high risk of significant 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 fully participate in the study. 8. Patients receiving any vaccination (including live attenuated, toxoid and subunit) within 14 days prior toVisit 1 (screening) or during the course of the study. Influenza and human papillomavirus vaccines are allowed prior to study entry but are prohibited during the study. Tetanus vaccines are allowed prior to study entry and during the study. 9. Spontaneous or induced abortion, still or live birth within 4 weeks prior to Visit 1. 10. Use of oral anticoagulants or anti-platelet treatment regardless of route or indication (not including NSAIDS) within the 28 days (-1 day) prior to Visit 1 or at any time during the study. 11. Patients with a history of anti-phospholipid antibody syndrome. 12. 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. 13. History of malignant cancer, except the following treated cancers: cervical CIS, basal cell carcinoma or squamous cell carcinoma provided that the cancer is not current and treatment has been completed. 14. History of treatment with investigational human or chimeric antibodies within 3 months. History of treatment with belimumab (Lymphostat B), or CTLA4-Ig within 6 months, or with rituximab or other anti-B-cell antibodies within 12 months. The use of investigational agents, not specified above, including other investigational biologic or device products, within 28 days prior to Visit 1 (screening) or during the study. Use of the following medications in Table 9:1 of the protocol regardless of route, are prohibited within the time frame (wash-out period) as listed in the table prior to Visit 2 and the first infusion of study medication, or at any time during the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
responder rate at week 12 according to a combined response index. |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
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.8.3 |
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 | 20 |
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 | Information not present in EudraCT |
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 |
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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 | |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |